3.4ResearchDayAbstractBooklet

Meharry Medical College 69th Annual Research Day

Wednesday, March 5 and Thursday, March 6, 2025

Cal Turner Family Center

Agenda

Wednesday, March 5, 2025

8:30 a.m. Poster set ups and Breakfast

9:30 a.m. Opening Remarks, Dr. Anil Shanker, SVP, Office for Research & Innovation

9:45 a.m. Welcome Address, Dr. James E.K. Hildreth, President & CEO, Meharry Medical College

10:00 a.m. Introduction to Presentation Categories Dr. Michael Caldwell, AVP for the Office for Research & Innovation

10:15 a.m. Poster Presentations

12:15 p.m. Lunch Break

1:00 p.m. Virtual Poster Presentations

2:00 p.m. Introduction of Keynote Speaker - Ms. Destiny Ball Doctoral Candidate, President, Graduate Students Association, School of Graduate Studies

2:10 p.m. Keynote Lecture - Dr. Thirumala-Devi Kanneganti Title: “Molecular Mechanisms of Innate Immunity and Inflammation in Health and Disease”

3:15 p.m. Invited Oral Presentations of Outstanding Abstracts

4:45 p.m. Day 1 Adjourned

Thursday, March 6, 2025*

10:00 a.m. Introduction of Speaker - Ms. Octavia Ailsworth, MPH student, School of Global Health

10:15 a.m. Keynote Lecture - Dr. Glenn Ellis

Title: “From Protocol Design to Publication: Bioethics as a Thread for Research Integrity”

11:30 a.m. Lunch Break

12:30 p.m. Community Engagement SessionDr. Stephania Miller-Hughes, Professor, Department of Surgery, School of Medicine

Dr. Leah Alexander, Professor & Chair, Department of Public Health, School of Global Health

Title: “Resources Available with the Community Engagement Core at Meharry”

2:30 p.m. Awards Presentation - Drs. Awadh Binhazim and Aramandla Ramesh, AVPs for the Office for Research & Innovation

3:00 p.m. Acknowledgements

3:15 p.m. Research Day Adjourned

*All events will be held in the Wayne J. Riley, M.D. Auditorium at the Cal Turner Family Center

Keynote Speaker

Thirumala-Devi

Kanneganti, PhD Director, Center of Excellence for Innate Immunity & Inflammation

St. Jude Children’s Research Hospital, Memphis, TN

Dr. Thirumala-Devi Kanneganti is a world-leading expert in the fields of innate immunity, cytokines, inflammasomes, and inflammatory cell death. She currently serves as a Member and Vice Chair of the Immunology Department and Director of the Center of Excellence for Innate Immunity and Inflammation, and she holds the distinguished Rose Marie Thomas Endowed Chair at St. Jude Children’s Research Hospital.

As a founding member of the inflammasome field, Dr. Kanneganti’s research has yielded fundamental insights into innate immunity, inflammation, and cell death. Notably, Dr. Kanneganti’s studies identified NLRP3, ZBP1, NLRC5, NLRP12, and AIM2 as key innate immune sensors, and she elucidated their upstream regulatory mechanisms, significantly advancing our understanding of biological processes. Dr. Kanneganti has also pioneered the concept of the inflammatory cell death pathway, PANoptosis, and her research has bridged major gaps in the fields of innate immunity, cell death, and inflammation. Beyond discovering the genetic basis and molecular mechanisms of interacting networks of innate immune sensors and cell death components, her work has established governing biological principles and the physiological relevance of key inflammatory pathways in infections, inflammatory diseases, and cancer. She has also significantly moved the cytokine field forward and identified regulatory mechanisms and functions for IL-1 family members, and the synergism between TNF and IFN-γ, which induces inflammatory cell death and the “cytokine storm.” Consistently recognized for her exceptional contributions, Dr. Kanneganti has been named one of the world’s most highly cited researchers for seven consecutive years by Clarivate Analytics. She has also received the International Cytokine and Interferon Society Milstein Award for Excellence in Interferon and Cytokine Research, she is a Fellow in the American Academy of Microbiology and the American Association for the Advancement of Science, and she received the 2024 American Association of Immunologists-Thermo Fisher Meritorious Career Award. By continually advancing basic and translational research, she remains at the forefront of her field.

Keynote Speaker

Glenn Ellis, MPH, CHCE, DSc (h.c.), FCPP Medical Ethics-Health Communication-Advocacy President, Strategies for Well-Being, LLC

Philadelphia, PA

Dr. Glenn Ellis Sr. is a renowned medical ethicist, researcher, lecturer, and president of Strategies for WellBeing, LLC. He focuses on health education, equity, disparities, advocacy, policy, and communication. Ellis has dedicated his career to championing the ethical protection of patient rights, especially for African Americans and other underserved groups.

Dr. Ellis’ extensive research and publications further underscore his impact on health equity and ethics. He has authored and co-authored numerous papers in prestigious journals, including the American Journal of Public Health, the American Journal of Academic Medicine, the Journal of Philosophy and Ethics, and the Journal of Healthcare, Science, and the Humanities. His books, such as Which Doctor? (2008), Information is the Best Medicine (2012), and forthcoming titles A Rising Tide Lifts All Boats: Narrative Essays on Bioethical Dilemmas (2024) and The Heart of the Matter: A History of Medicine and its Messengers (2025), are part of the broad body of work that contributes to Ellis’ commitment to healthcare, medicine, and public health.

Dr. Ellis’ speaking engagements span a wide array of national and international conferences. He addresses crucial topics including cultural and ethical considerations in end-of-life care, the retention and recruitment of underserved populations in clinical research, and the ethical implications of race and ethnicity in clinical settings. Ellis has lectured or presented at esteemed institutions. They include Thomas Jefferson University, Howard University Hospital, Loyola University Chicago and Ghent University, He has participated in global forums like the UNESCO Chair in Bioethics World Conference and the International Symposium on Bioethics in Kyiv, and Public Responsibility in Medicine and Research (PRIM&R).

In addition to his academic and media contributions, Dr. Ellis served for many years on multiple institutional review boards and ethics committees in Philadelphia: Mercy Health System, Thomas Jefferson Health System, and Drexel University Health System. Dr. Ellis has received numerous honors, including the Pennsylvania NAACP Award for Health and Medicine, the City Council of Philadelphia’s recognition for his contributions to medicine and public health education, and an Honorary Doctorate in Science from Oakland University. His expertise and influence in health equity and ethics continue to impact public health and medical research significantly. In 2024, Ellis received an honorary doctorate in Science (D.Sc.) from Oakland University and is currently completing a doctorate in Global Bioethics.

School of Applied Computational Sciences

Poster SACS-1

KNOWLEDGE GRAPH EMBEDDING MODELS FOR DRUG REPURPOSING

Bradford Patton, Jaylin Dyson, Cameron Pykiet, Abdullah Al Mamun, Bishnu Sarker

School of Applied Computational Sciences, Meharry Medical College, Nashville, TN

Discovering treatments relies on unraveling their molecular basis, a costly and labor-intensive endeavor. Artificial intelligence and deep learning aim to expedite this process by integrating biomedical databases like UniProtKB, OMIM, and BioGrid. However, current machine learning techniques face limitations in modeling biological entities, integrating diverse data sources, and providing explanations. Knowledge Graph (KG) interconnects heterogeneous biomedical entities for more comprehensive analysis using Knowledge Graph embedding (KGE). KGE models compute low dimensional vector representation for the knowledge graph entities and relations to build downstream predictive models such as link prediction, node prediction. The primary benefits of KGs are 1) easy integration of data from multiple sources, 3) explainable decision making while using existing machine learning techniques. In this research we, 1) curate a KG to include external biomedical information about diseases, 2) develop a machine learning pipeline to predict the repurpose-able drugs for diseases. Experiment-wise, we have run 27 KGE models on a biomedical knowledge graph with 111,171 entities, 16 relation types, and 2,132,796 edges prepared using BioKG. We identified 6 models that performed with a hit@10 at least 0.50. We then applied these models to find repurposable drugs for Mesothelioma, a rare disease. This work provides extended insights on the performance as well as challenges in terms of variability of the model’s outcome to retrieve meaningful drug repurposing outcomes.

This material is based upon work partially supported by the National Science Foundation under Grant No. 2302637.

Poster (Virtual) SACS-2

DYNAMICS

OF MULTIPARTITE VIRUS INFECTIONS: A MATHEMATICAL AND COMPUTA-TIONAL STUDY OF BIPARTITE VIRUS MODEL

Dyani Peterson1, Lubna Pinky1

Department of Biomedical Data Science, Meharry Medical College, Nashville, TN

Some viruses consist of several separate strands of RNA or DNA rather than one long string of either. Multipartite viruses package the separate strands of RNA/DNA in separate packages that are released from the infected cell. To infect a new cell, the cell must receive at least one copy of each of the strands. This seems to be an inefficient way to propagate an infection, so researchers have long wondered why such viruses persist. This project aims to examine infection of multipartite viruses using a series of mathematical models to see if there is some behavior that might be advantageous for spread of infection. To better understand multipartite virus dynamics, we developed a system of ordinary differential equations to describe interactions between target cells, partially infected cells with one particle, fully infected cells with both particles, and two types of viral particles. The bipartite virus model incorporates infection rates for each particle, particle production rates, clearance rates and reversion rates, meaning partially infected cells revert to target cells. Stability analysis was conducted to identify steady states and assess their stability. Simulations were performed using Python’s odeint solver with parameter values derived from influenza infection data. The analysis suggests that higher infection or production rate, or a larger initial number of viral particles, generally lead to higher corresponding particle peak. The time to reach peak decreases as infection or production rate increases. However, the peak times appear to be relatively constant across different initial conditions, indicating that the timing of viral peaks is more dependent on system parameters than on initial conditions. Low or asymmetric infection or production rates allow for coexistence or prolonged dynamics with slower infection progression. Our analysis provided insights into the sensitivity of bipartite viral dynamics to variations in the parameters.

RACIAL DIFFERENCES IN FEATURES ACROSS MESA, SHHS, CFS, MROS, AND WSC DATASETS: UNDERSTANDING ATTRIBUTE BIASES

Evann Bailey, Shumit Saha

Department of Biomedical Data Science, School of Applied Computational Sciences, Meharry Medical College

Machine learning (ML) models in sleep apnea diagnosis have shown promise for improving diagnostics and personalized treatment. However, algorithmic biases in training data can lead to suboptimal outcomes and inequities in patient care. This study aims to investigate racial differences in key sleep-related variables across multiple datasets: MESA (Multi-Ethnic Study of Atherosclerosis), SHHS (Sleep Heart Health Study), CFS (Cleveland Family Study), MrOS (MrOS Sleep Study), and WSC (Wisconsin Sleep Cohort). The goal is to identify potential variables that may impact the fairness of predictive models by highlighting features that differ between races in one dataset but not in others. This approach emphasizes the risk of using such variables in machine learning models due to potential attribute bias, which could lead to suboptimal predictive outcomes and exacerbate healthcare disparities We identified the same variables that existed in the MESA, SHHS, CFS, MrOS, and WSC datasets, focusing on their distribution across White and Black racial groups. Unpaired t-tests were conducted to determine whether the mean differences between the two racial groups were statistically significant (p < 0.05). We further assessed which variables were significant in one dataset but not in others, identifying potential inconsistencies that could contribute to bias if used in machine learning models.

Our analysis identified 92 important sleep-related variables that showed significant differences between White and Black populations in one dataset but not the other. a) Oxygen Saturation: We identified 4 variables that are related to duration of sleep with oxygen saturation ranging from 75-90 percent (variables significant in MESA, not in MrOS). b) Obstructive Apnea Index: We identified 4 variables related to the Obstructive Apnea Index during REM sleep, in different body positions (supine and non-supine), oxygen desaturation thresholds, and arousal (variables significant in MESA, not in CFS). c) Epworth Sleepiness Scale: 2 variables were identified in relation to frequency of daytime sleepiness (variables significant in MESA, not in WSC). d) Apnea Ratio: We identified 3 variables that represent the ratios of central without an oxygen desaturation threshold to obstructive apneas (variables significant in MESA, not in SHHS).

The study’s findings reveal that several sleep variables demonstrate significant racial differences in the MESA dataset but not in the SHHS, CFS, MrOS and WSC datasets. This inconsistency suggests that using such variables in machine learning models may lead to attribute bias, potentially skewing model outcomes and disadvantage underrepresented groups, particularly Black populations.

Grant Funding: NIH AIM AHEAD, Grant No - 1OT2OD032581-02-838

Poster (Virtual) SACS-4

IDENTIFYING SURGERY TYPE FROM VOWEL SOUNDS: TONSILLECTOMY, SEPTOPLASTY, AND FESS AT 15 DAYS POST-OP

Habeeb Kotun Jr.1, Shumit Saha1 School of Applied Computational Sciences, Meharry Medical College

Vowel sounds have shown to be a great potential biomarker for diagnosing diseases such as sleep apnea, asthma, and COPD. However, ENT surgeries such as Tonsillectomy, Septoplasty, and Functional Endoscopic Sinus Surgery (FESS) may alter the generation of vowel sounds. Therefore, it is important to understand the short- and long-term effect of these surgeries on vowel articulation. This study aimed to predict the type of surgery using vowel sounds recorded 15 days post-surgery.

We performed a retrospective study on an opensource dataset from the Otorhinolaryngology Service of Hospital Universitario de Fuenlabrada, Spain, containing /a/, /e/, and /i/ vowel recordings from patients who underwent Tonsillectomy, Sep-

toplasty, or FESS. We extracted 363 domain features from the patients’ audio 15 days after their surgery. Random forest models were trained using 5-fold cross-validation to predict the type of surgery, with F1 score as the evaluation metric. F1 scores on the test set were Septoplasty vs. Tonsillectomy (0.847), FESS vs. Tonsillectomy (0.692), and FESS vs. Septoplasty (0.681). Figure 1 shows confusion matrices for each classification.

Our findings demonstrate that vowel sounds can identify surgical procedures, offering a non-invasive tool for post-surgical monitoring and care. Future work should focus on expanding the dataset to include a more diverse patient population and additional vocal surgical categories.

Poster SACS-5

GENEA: A GENE SET ENRICHMENT ANALYSIS TOOL USING PYTHON AND STREAMLIT

Jaylin Dyson1, Jamaine Davis2, Bishnu Sarker1

1Department of Computer and Data Sciences, School of Applied Computational Sciences, Meharry Medical College,

2Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Medicine, Meharry Medical College

We present a gene enrichment analysis app named GenEA developed using Python programming language and Streamlit app development platform. As a case study, we demonstrate the use of GenEA for comprehensive gene enrichment analysis of BRCA1 gene interactors. Understanding Protein-protein interaction (PPIs) is crucial for understanding physiology in normal and diseased states. The Breast Cancer Susceptibility protein 1, BRCA1, is an important protein for preventing tumor formation. This protein functions across a variety of cellular processes. Here we present a comprehensive gene set enrichment analysis of the BRCA1 interactors. As a first step, we identified sources of biomedical data relating to BRCA1. We retrieved the interactor proteins from BIOGRID database. There is a list of 1157 unique interacting proteins mapped to 1175 unique genes. We used GenEA interface to load the genes and let it perform gene set enrichment analysis. A comprehensive gene enrichment analysis was performed that includes functional enrichment (Gene Ontology), pathway enrichment (Reactome, KEGG), molecular signature (MSigDB), domain enrichment (InterPro, Pfam). A detail report was generated to show the signigicantly enriched characteristics. Additionally, a network visualization of the 1175 interactors of BRCA1 is generated using STRING database to help elucidate the intiricate relationship as well as to identify closely knitted clusters of the genes of high similarity. This analysis presents an unprecedented structure- and context-dependent view of protein interaction networks. These structure-informed networks will reveal mechanistic insights regarding cellular processes underlying human diseases ranging from cancer to those resulting from viral and bacterial infection. GenEA provides an easy to use framework for the quick gene enrichment analysis for the development of new hypotheses in understanding genotypes and associated phenotypes, as well as strategies for drugs that can target proteins in these networks.

This material is based upon work partially supported by the National Science Foundation under Grant No. 2302637 and RCMI supplemental grant.

Poster SACS-6

PRETERM BIRTH PREDICTION IN PATIENTS WITH GRAVES’ DISEASE: INSIGHTS

FROM NIH All of Us DATA

Judith Dike, Uma Sarder, Aize Cao

School of Applied Computational Sciences, Meharry Medical College, Nashville, TN

Graves’ disease is associated with various pregnancy complications. This study aims to investigate the relationship between Graves’ disease and preterm birth and examines the use of machine learning techniques to predict preterm disease using NIH All of Us electronic health records. We conducted a subgroup analysis of individuals diagnosed with Graves’ disease, differentiating between those who experienced preterm births and those who did not. This analysis included

demographic variables of age and race. Both Graves’ disease and preterm birth were identified using ICD10 codes. To predict the risk of preterm birth, we developed three machine learning models: Logistic Regression, Random Forest, and XGBoost. The performance of these models were evaluated based on accuracy and ROC-AUC scores. The study analyzed 1,923 individuals with Graves’ disease, including White (42.5%), Hispanic (35.3), Black (13.9%), Asian (4.7%), and Other (2.7%). Among these patients, 468 (24%) experienced preterm birth. Individuals with preterm birth had higher instances of Graves’ disease events (7.68 vs. 2.76) and were slightly younger on average (29.45 vs. 30.97 years). A Chisquare test indicated a significant association between race and preterm birth (p value=0.032). The logistic regression model achieved 79% accuracy, but only 19% recall for preterm birth. XGBoost demonstrated the best recall for preterm birth (38%) with 68% accuracy. The Random Forest model showed moderate performance with an ROC-AUC score of 0.6203. The study revealed associations between Graves’ disease severity, age, race, and preterm birth risk. While our machine learning models show potential in predicting preterm birth, their performance indicates challenges in achieving high precision and recall simultaneously. We are investigating more risk factors that potentially contribute to the development of preterm birth and exploring machine learning algorithms to improve predictive performance.

Poster (Virtual) SACS-7

MACHINE LEARNING-BASED CLASSIFICATION OF APNEAS AND HYPOPNEAS USING NASAL AIRFLOW SIGNALS

Kweku White, Shumit Saha

School of Applied Computational Sciences, Meharry Medical College

Obstructive Sleep Apnea (OSA) is characterized by partial or complete upper airway collapse, leading to hypopneas and apneas, respectively. Nasal airflow signals are a key physiological marker for distinguishing these respiratory events. This study aims to classify apneas and hypopneas using machine learning (ML) models to enhance diagnostic accuracy

A retrospective analysis was conducted using data from the Multi-Ethnic Study of Atherosclerosis (MESA) dataset. A subset of 100 participants was randomly selected. Fourteen features, including flow limitations and airflow flattening, were extracted from nasal airflow signals. Multiple ML models, including Logistic Regression, Decision Trees, Random Forests, and Deep Neural Networks, were implemented for classification. Hyperparameter tuning and 5-fold cross-validation were applied to optimize model performance and mitigate overfitting.

Among the evaluated models, the Random Forest classifier achieved the highest performance, optimized with 200 trees, a maximum depth of 20, and balanced class weights. The final model achieved an accuracy of 65%, with sensitivity of 60% and specificity of 66%. In summary, this study demonstrates the feasibility of ML-based classification of apneas and hypopneas using nasal airflow signals.

Poster SACS-8

IMPACT OF RACIAL DIFFERENCES ON OSA DIAGNOSIS AND PREDICTIVE TOOLS: A SCOPING REVIEW

L Bien Aime, S Saha

Department of Biomedical Data Science, School of Applied Computational Sciences, Meharry Medical College

Obstructive sleep apnea (OSA) is a prevalent chronic respiratory disorder characterized by frequent upper airway collapse during sleep, leading to significant health risks such as stroke, hypertension, and heart disease. The gold standard for diagnosing sleep apnea, polysomnography (PSG), involves extensive sensor data collection, making it suitable for developing machine learning (ML) algorithms to improve diagnostic accuracy. However, existing ML models for sleep apnea diagnosis often lack explainability and fail to consider racial disparities. This scoping review aims to explore the impact of race on the diagnostic performance of these emerging OSA prediction models.

A scoping review was conducted by searching PubMed, Google Scholar, and IEEE Xplore for peer- reviewed studies published between 2011-2024. We only include studies that developed ML models for OSA prediction using physiological data such as airflow, abdominal signals, and ECG, with a report on race-specific results. We stratified race as African Americans, Caucasian, and Asian. We evaluated diagnostic performance by evaluating F1 score.

We observed racial impact in sleep apnea risk factors across retrospective and prospective datasets. Published works developed a deep learning model using oximetry signals and showed a performance drop for African American participants (Overall F1: 0.82, F1 for African American: 0.66). Some reports have shown race-based features can improve ML models accuracy by 11.93% Furthermore, other reports have shown that incorporating age, sex, BMI and race as the main input to ML models can perform similarly as current questionnaires (STOP-Bang: AUC 0.71, ANN and RF: 0.70), emphasizing the importance of race as a contributing factor in OSA assessment. In summary, this review emphasizes the necessity for OSA diagnostic tools to account for racial differences to achieve more personalized and accurate diagnosis.

This work was supported by the NIH AIM AHEAD, Grant No - 1OT2OD032581-02-838.

Poster (Virtual) SACS-9

AN EXPLORATORY ANALYSIS OF ALZHEIMER’S DISEASE TO ELUCIDATE LINK BETWEEN RACE TO RISK.

Loni S. Taylor, Gregory Gibbs, and Bishnu Sarker

School of Applied Computational Sciences, Meharry Medical College, Nashville, TN

The primary focus of this study is to analyze the differences in alleles and gene data for Apoliprotein E (APOE) of individuals who are of African descent in comparison with the entire population. The hypothesis is set to evaluate whether there will be a significant difference in the onset of the disease by race for alleles and genotypes. This relatability concept is determined by using preprocessing on the data to complete statistical analysis such as computing frequency and distribution tables for the racial groups classified in the data. The design of this study is to use biomarker and participant data of all visits for all participants provided from the National Alzheimer’s Coordinator Center (NACC) to complete an association-based analysis to determine the relatability of age, race, allele and gene distribution in the reported Alzheimer’s data. The population studied had a total 172026 records, 86% of which were white while subject data for African Americans detailed 14%. Results found that overall age did not change the distribution of the gene but may have basis to determine if race was a factor. One of the results of our study showed the differences in race and the APOE gene.

Poster SACS-10

THE IMPACT OF EDUCATION IN SOCIAL DETERMINANTS OF HEALTH FOR INCLUSIVE GROWTH SCORES IMPROVEMENT

L. Taylor, L. Bien Aime, MJ. Paul, S. Saha

Department of Biomedical Data Science, School of Applied Computational Sciences, Meharry Medical College Educational attainment drives economic mobility and social determinants of health (SDoH) with lower performance on standardized assessments resulting in reduced income, exacerbated health disparities, and lower inclusive growth scores (IGS)-the measurement of the economic and social health of neighborhoods. This study investigates the relationship between education, income growth, and community development, emphasizing the impact of education on IGS as a predictive measure for community progress.

We used datasets from Mastercard IGS, U.S. Census, and 20 Education Service Centers for Texas K-12 assessments. Districts serving communities statewide totaled approximately 1100 instances for the category assessed (Grade 3 Reading). Alief’s community’s outcomes were chosen for being under the threshold value set at 45 for low IGS to compare across the state with communities with high IGS greater than 45 serving the same number of students. Three communities were chosen to compare against as exemplars as they serve similar demographic populations as Alief. We employed linear and logistic regression models to predict how the educational attainment may change as a result of factors recorded from the

SDoH variables (census data) and their impact on the changes recorded in the IGS score.

We found that the low IGS community has lower educational attainment and lower income level than the high IGS community. We also found 82.6% accuracy in predicting the IGS score with SDoH variables, where we showed increases in the educational attainment improved the score.

Inclusive growth scores improve (State level) as community scores improve. This study underscores the necessity of strategic educational interventions as a catalyst for long-term community development, measured by IGS score.

Poster SACS-11

EFFECT OF OBESITY ON UPPER AIRWAY AREA: INSIGHTS FROM MRI AND VOWEL ANALYSIS

Noah Whittenbarger, Kweku White, B.S, Habeeb Kotun Jr, Shumit Saha

School of Applied Computational Sciences,

Meharry Medical College

Upper airway (UA) area assessment is critically important because UA narrowing presents an increased risk of perioperative complications after anesthesia. Vowel sounds could be an effective tool to assess UA, as back and frontal vowel change the shape of the UA. This study aimed to investigate the effect of body mass index (BMI) on UA area during vowel articulation and predict MRI-based UA area from vowel audio features. We performed a retrospective study using an open-source dataset from the LA county-USC Medical Center. The dataset included MRI videos and sound files when participants articulate vowels: “/a/” and “/i/”. We manually segmented the UA area from vellum to epiglottis for /a/ and /i/ vowels. We then standardized images to 3028 x 2102 pixels and calculated the number of pixels within the segmentation.

We divided the participants into 4 BMI groups (Group 1: 16.53 – 20.70, Group 2: 20.70 – 23.46, Group 3: 23.53 – 26.28, Group 4: 26.59 – 34.45). We then performed two repeated measure ANOVA to investigate the variation from /i/ to /a/ between groups to investigate the effect of obesity. For prediction, we implemented an Ada-boost regression model to predict the UA area for /i/ and /a/.

The variation of UA area from “/i/” to “/a/” was significantly smaller in high BMI group than low BMI group (High: ∆61893.16 ± 22109.41 pixels vs. control: ∆74096.48 ± 26427.27 pixels, p < 0.05). For /i/ and /a/ vowels, we achieved r2 values of 0.42 and 0.4, respectively, between predicted and measured UA area.

Our preliminary results show that UA area varies significantly during vowel articulation across BMI, could be due to bigger tongue or more fat in the tongue. Furthermore, vowel sounds can be used to predict the UA area, demonstrating the potential of voice to be used as a UA assessment tool.

Poster SACS-12

CRANIOFACIAL VARIATIONS IN AFRICAN AMERICANS AND THEIR IMPACT ON SLEEP APNEA: A SCOPING REVIEW

Tenesha Boyd1, Shumit Saha2

1School of Medicine, and 2School of Applied Computational Sciences, Meharry Medical College

Polysomnography remains the most reliable method for diagnosing obstructive sleep apnea (OSA), but its high cost and limited accessibility necessitate alternative diagnostic approaches, such as speech-based and facial imaging tools. These methods rely on anatomical and physiological features that vary across populations. In particular, African Americans exhibit distinct craniofacial and upper airway characteristics that may influence OSA risk. This scoping review examines

these anatomical and physiological differences to support the development of diagnostic tools tailored to this population.A scoping review was conducted using PubMed, Connected Papers, and Google Scholar to identify peer-reviewed studies published between 2011 and 2022. Eligible studies focused on craniofacial and upper airway features assessed through imaging techniques (e.g., MRI, CT, 3D scans) and physiological measurements (e.g., airway collapsibility, loop gain). Studies that lacked subgroup analyses or relevant data were excluded.

African Americans demonstrated distinct OSA-related risk factors compared to other populations. Studies reported that African American males had higher apnea-to-hypopnea ratios and a more collapsible airway, along with reduced loop gain, which may contribute to OSA severity. Additionally, other studies reported that African Americans exhibited larger tongue volumes (+15–20%) and greater pharyngeal fat deposits (+30–40%), factors that increase airway obstruction risk. In terms of craniofacial structure, some literature reports revealed that African Americans were more likely to exhibit dolichocephalic features (elongated facial height), which may contribute to airway differences and OSA susceptibility.

These findings highlight key anatomical and physiological traits in African Americans that influence OSA risk. Future diagnostic tools should incorporate these population-specific characteristics to improve accuracy and effectiveness in detecting and managing OSA.

Oral presentation SACS-13

IMPACT OF SOCIOECONOMIC STATUS ON MATERNAL MENTAL HEALTH DISORDERS IN THE U.S. WOMEN USING

NIH All of Us DATA

Uma Sarder, Aize Cao

School of Applied Computational Sciences, Meharry Medical College, Nashville, TN

Maternal mental health, particularly depression and anxiety are crucial to the well-being of pregnant women. Until recently, maternal mental health was primarily addressed after childbirth, with a focus on conditions like postpartum depression (PPD). Nowadays, maternal mental health is increasingly recognized as a critical aspect of care from conception through antenatal care, labor, and into the postpartum period. Even though the impact of socioeconomic factors on mental health is increasingly recognized, a comprehensive study examining the associations between socioeconomic status and maternal mental health disorders has yet to be conducted. Understanding the complex interplay between socioeconomic, depression, and anxiety across different racial groups of pregnant women is crucial for developing effective preventive measures and treatment strategies aimed at reducing maternal and fetal mortality. This study utilized data from the All of Us initiative to examine the relationship between socioeconomic and maternal mental health disorder, especially depression and anxiety.

We conducted a retrospective cohort study, including women aged 18-55 who had at least one defined pregnancy in All of Us research program from Jan 1, 2018, to Dec 31, 2023. The pregnancy was identified using CMS official guidelines for ICD10 coding and reporting (2023). Index pregnancy visit was identified as the first visit of each pregnancy. Key socioeconomic factors, including education level, marital, health insurance, employment, and income, were considered as potential predictors. The outcome of this study were depression and anxiety disorders, identified using ICD10 codes based on the Elixhauser Classification. Depression and anxiety disorder were captured by considering within a range from 4 months prior to the pregnancy start date up to 12 months following the pregnancy start date.

The study identified 9,513 women who had at least one ICD10 pregnancy codes, with a median age of 30 years (IQR: [26,35]). They were Hispanic or Latino (45.6%), White (32.1%), Black (14.2%), Unknown (3,7%), and Asian (3.5%). Overall, 9% (856) of the participants had depression, and 9.1% (863) had anxiety disorder during pregnancy. The adjusted odds ratios from the logistic regression indicated that women who were separated, unemployed, had an income below 10K, or had less than eleventh grade education were at higher risk for depression and anxiety disorders. Marital, employment, education level, and income were strongly associated with depression and anxiety disorder during pregnancy time. Whether these factors could be leveraged to reduce the maternal mental health risk should be investigated.

This work is supported by HRSA grant UR650342.

USING GIS AND METAGENOMICS TO ENHANCE WASTEWATER SURVEILLANCE

Victoria Love Franklin, Gary Todd, Lubna Pinky, Bishnu Sarker

Department of Biomedical Data Science, School of Applied Computational Sciences, Meharry Medical College

Wastewater surveillance provides essential information on pathogen distribution and community health; it has become increasingly important for public health monitoring. This study includes the use of Geographic Information Systems (GIS), which provides a spatial analysis of disease distribution, with metagenomics, which identifies organisms present in wastewater by DNA sequencing. With the help of these analytical tools, we hope to develop a wastewater monitoring system that provides enhanced geographical resolution and insights into disease trends. Meharry’s School of Applied Computational Sciences (SACS) will host and develop this monitoring system, giving the organization a new wastewater surveillance capability.

Our Objective is to implement an innovative wastewater surveillance system that utilize Geographic and metagenomics. Doing so will provide information regarding the distribution of pathogens and provide better approaches to public health interventions. Our key objective is to establish this capability within Meharry’s SACS. Our method of gathering wastewater samples is by choosing designated locations within a geographic area, to capture the temporal and spatial distribution of pathogens. DNA will be extracted from the samples using high-throughput sequencing. The data will then be processed using bioinformatics tools to determine the relative abundance of the organisms that are present. The ArcGIS environment will be used to map the locations of the wastewater sample. Spatial Techniques such as spatial interpolation, hotspot, and overlay analysis will be used to analyze the metagenomic wastewater data within the ArcGIS environment. We aim to analyze the geographical patterns of pathogen distribution and their correlation with the relevant data such as census data (population density, socioeconomic indicators) and environmental data (weather and land use).

The expected results are to: i) show the advantages of integrating GIS and metagenomics for wastewater surveillance; ii) Identify distinct spatial patterns in pathogen distribution, and reveal correlations with census and environmental factors, including community health; iii) map the spatial distribution of key pathogens in wastewater; iv) Identify hotspots of highest pathogen concentration; iv) correlate pathogen presence with census and environmental variables; and v) establish a robust and sustainable wastewater surveillance system at Meharry’s SACS.

School of Global Health

SCOPING REVIEW OF HEALTH EDUCATION AND HEALTH PROMOTION PROGRAMMING AT HBCUS: ENHANCING STUDENT WELL-BEING AND INCREASING HEALTH EQUITY

C. Felder1, EC. Stewart1, Q. Beacham1, VL. Brown1, JC. Erves2

1Department of Public Health, School of Global Health, Meharry Medical College, and 2Vanderbilt University Medical Center

This scoping review examines health education and health promotion programs at Historically Black Colleges and Universities (HBCUs) focusing on their characteristics, target populations, intervention strategies, and intended health outcomes. Given HBCUs’ role in addressing health disparities within African American communities, this review seeks to comprehensively assess the scope of health initiatives tailored to their student populations. Following the JBI Framework and PRISMA guidelines, we conducted systematic search was conducted across major databases including PubMed, CINAHL, PsycINFO, and ERIC. The search strategy, developed with a Meharry Medical College reference librarian, identified English-language studies published within the past 15 years. Eligible studies examined health education and promotion programs for HBCU students addressing chronic disease prevention, mental health,

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sexual health, and substance use. Studies were excluded if they did not focus on HBCU students, were not health-related programs, or fell outside the specified time frame.

Initial analysis of qualitative and quantitative data revealed themes in HBCU health programming including chronic disease prevention, mental health awareness, sexual health education, and substance abuse prevention. Programs consistently featured peer-led initiatives, community partnerships, and culturally tailored approaches. However, gaps emerged in standardized evaluation metrics, long-term outcome assessments, and program sustainability strategies.

This review underscores HBCUs’ contributions in advancing health equity through culturally relevant programs. While existing initiatives address pressing health disparities, findings indicate the need for more robust evaluation frameworks and comprehensive research on long-term impacts. These insights establish a foundation for developing evidence-based sustainable interventions that can effectively improve health outcomes and promote equity among HBCU student populations. Future research should focus on strengthening program evaluation methods and examining longitudinal effects to enhance the effectiveness of health promotion efforts within HBCU communities.

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INVESTIGATING COLLEGIATE BLACK MEN’S HEALTH RESEARCH: A SCOPING REVIEW

1Q. Beacham, 1EC. Stewart, 1C. Felder, 1VL. Brown, 2JC.

Erves

1Department of Public Health, School of Global Health, Meharry Medical College, and 2Vanderbilt University Medical Center

This scoping review systematically evaluates research on the health experiences, outcomes, and interventions among Black men in collegiate settings. It explores health disparities, healthcare access, and wellness domains while examining the intersection of race, gender, and academic environments in shaping health outcomes. Findings aim to inform evidence-based institutional support services and guide future research directions.

Using the JBI framework and PRISMA guidelines, searches were conducted across PubMed, CINAHL, PsycINFO, and ERIC databases with the support of a Meharry Medical College reference librarian. The review included English-language studies published from 2015 to 2024, employing search terms related to Black/African American men, collegiate populations, and health domains. Two independent reviewers screened sources and extracted data using standardized forms, focusing on study characteristics, methodologies, and key findings.

Preliminary analysis reveals a predominant focus on mental health, psychosocial well-being, and challenges associated with the college transition. Key themes include the role of social support networks, the influence of masculine norms on health-seeking behaviors, and barriers to healthcare access. Research gaps are evident in preventive care, physical health interventions, and longitudinal health outcomes. Emerging evidence highlights the value of peer support programs and culturally competent health services in improving health outcomes.

This review underscores critical gaps and emphasizes the need for culturally responsive approaches tailored to the unique sociocultural contexts of Black male college students. The findings will inform actionable recommendations for healthcare providers, university administrators, and policymakers to strengthen support systems, reduce health disparities, and promote holistic well-being. Moreover, it establishes priorities for future research and intervention development targeting this population.

MATERNAL MENTAL HEALTH AMONGST BLACK WOMEN: A TENNESSEE PRAMS ANALYSIS

T. Watts, C. Harris, L. Alexander

Department of Public Health, School of Global Health, Meharry Medical College

Postpartum depression (PPD) is a mood disorder occurring after birth that disproportionately impacts Black women. Nearly 1/3 of maternal deaths among black women are related to mental health conditions. Studies have suggested that 29-44% of black women experience postpartum depressive symptoms. The purpose of this study is to examine how social determinants of health and prenatal factors affect PPD in Black women in Tennessee.

A systematic literature review was conducted to confirm variables believed to be related to PPD. Phase 8 data from Tennessee’s Pregnancy Risk Assessment Monitoring System (PRAMS) will be obtained from the Tennessee State Health Department. Variables will include demographics, pregnancy intention, socioeconomic status, healthcare access, health behaviors, and prenatal factors. These prenatal factors include weight, stress, and WIC participation. Once approved by the State Health Department Institutional Review Board, logistic regression will be used to analyze data from 2017-2021.

It is expected that there will be a significant relationship between postpartum depression and socioeconomic status, healthcare access, and pregnancy intention among Black women in Tennessee. We anticipate our findings will underscore the importance of addressing postpartum depression among Black women in Tennessee by highlighting structural inequities, health disparities, and systemic barriers to maternal mental health care for Black women. Our findings will provide a foundation for culturally tailored interventions designed to reduce postpartum depression among Black women in Tennessee.

Funding Source: HRSA

School of Dentistry

WHEN MANAGING A TRAUMATIC DENTAL INJURY GOES WRONG: EXTRUSION AND ENAMEL FRACTURES OF MAXILLARY CENTRAL INCISORS

Melissa D. Porter1, Jada Pierre2, Kristin Smith2, Taylor Swett2 , Alexis Jackson2 , Mirissa Price3 , Zaid Khour4

1Department of Pediatric Dentistry, Pediatric Residency Program, School of Dentistry, Meharry Medical College, Nashville, TN.

2School of Dentistry, Meharry Medical College

3Department of Pediatric Dentistry, School of Dentistry, Meharry Medical College

4Department of Oral Diagnostic Sciences & Research, School of Dentistry, Meharry Medical College

Traumatic dental injuries (TDIs) are frequently encountered in both children and adults, often resulting from accidents (including motor vehicle), physical activity, or abuse. In the permanent dentition, tooth displacement accounts for 15-61% of traumatic episodes, with most TDIs occurring in children between the ages of 2-6 and 13-16. The management of these injuries will vary according to their severity and the length of time that elapses between injury and care. This case report discusses the dental management and subsequent sequela of a non-compliant 11-year-old African American male who experienced an accident at school. The patient sustained extrusion of tooth #8 and enamel fracture of tooth #9. At the time of the study, the patient was followed for 4 months post-trauma. Extrusive luxation is a rarely encountered TDI that occurs due to partial displacement of a tooth from the socket and is characterized by loosening of the periodontal ligaments (PDL), changes to the pulp status, and increased tooth mobility. TDIs result in lifelong time-consuming and

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costly dental treatment. This case highlights the exaggeration of both these non-clinical and clinical negative sequelae in the event of non-compliance. It further demonstrates the importance of ensuring: (1) patient/parent and provider expectations, (2) patient education and (3) patient compliance to result in optimal post-injury care.

This research was partly funded by the 1) HRSA-COE Grant (D34HP00002) (support dental student research) to the Meharry Medical College, School of Dentistry

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EXPLORING THE MICROBIOME LANDSCAPE OF DENTAL PLAQUE: A CROSS-SECTIONAL ANALYSIS IN PERIODONTAL HEALTH AND DISEASE

Ankineedu Babu Dasar1, Ramanarayana Boyapati 2, Rama Brahmam Lanke 2, Manasi Chinnadurai Mudaliyar 2 , Bhavyasri Gaddam2, Ravindranath Dhulipalla2

1Meharry Medical College School of Dentistry, Nashville, TN 37208

2Department of Periodontics SIBAR Institute of Dental Sciences, Takkelapadu, Guntur, Andhra Pradesh, India.

This study aimed to comprehensively analyze the microbiome of dental plaque in individuals with varying periodontal statuses, encompassing both periodontal health and disease. The primary objectives were to identify microbial markers associated with different clinical conditions, explore variations in microbial diversity, and investigate potential correlations between the oral microbiome and clinical parameters. A cross-sectional design was employed, involving 164 participants aged 18 to 65 years. Inclusion criteria comprised individuals with good oral and systemic health for the periodontal health group and those diagnosed with various stages of periodontal disease for the periodontal disease group. Dental plaque samples were meticulously collected from diverse tooth surfaces, and clinical examinations were conducted to assess periodontal health status. High-throughput sequencing of the 16S ribosomal RNA (rRNA) gene was utilized for microbiome analysis. Demographic characteristics revealed a balanced distribution between the periodontal health and disease groups. Clinical parameters, including probing depth, clinical attachment loss, and bleeding on probing, exhibited significant differences between the two groups (p < 0.001). Microbial diversity indices indicated a higher diversity in the periodontal health group compared to the disease group (p < 0.001). Analysis of relative abundance of bacterial phyla identified significant variations, with Firmicutes, Bacteroidetes, and Actinobacteria showing differential prevalence between health and disease (p < 0.05). Differentially abundant taxa analysis highlighted specific species associated with each clinical condition, including Prevotella intermedia and Porphyromonas gingivalis. Network analysis revealed complex microbial interactions within the oral microbiome. Functional predictions indicated variations in metabolic capabilities between health and disease, with potential implications for virulence and antibiotic resistance. This study provides a comprehensive analysis of the oral microbiome in periodontal health and disease, revealing significant associations between microbial composition and clinical parameters.

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EFFECTIVENESS OF NON-PHARMACOLOGICAL BEHAVIORAL GUIDANCE TECHNIQUES IN PEDIATRIC DENTISTRY: A LITERATURE REVIEW

Aryagne Dos Santos, Micah Armstrong, Blair Jason, Lauren Jordan, Jalen Sims, LaurenWaller and Mirissa Price

Department of Pediatric Dentistry, School of Dentistry, Meharry Medical College, Nashville, TN

Dental fear and anxiety (DFA) can affect people of all ages, but typically first develops in childhood and adolescence. DFA often originates from negative past experiences, inherited anxieties from parents, and concerns about pain or discomfort during treatments. These factors, along with unfamiliarity with the dental environment and general anxiety, can significantly heighten a child’s fear of dental visits. Implementing behavioral guidance techniques is one of the most reliable methods for reducing anxiety in pediatric dental practice. This literature review aimed to evaluate the current

reported effectiveness of non-pharmacological behavioral guidance techniques in managing pediatric dental anxiety. In recent years, behavior guidance has become more sophisticated to include technology, psychotherapy, and both active and passive approaches to distraction. Thorough search of the literature, 52 articles returned, of which 20 met the inclusion criteria for analysis in this study. The studies focused on methods such as tell-show-do, audiovisuals, virtual reality, dental storybooks, and active distraction. The analysis revealed high effectiveness across these non-pharmacological behavior guide techniques with tell-show-do being the most effective overall when combined with other methods. It was noted that current behavior guidance studies lack a standardized measurement tool; this underscores the need for further research to develop reliable and consistent methods for assessing and managing dental anxiety in children. As the field evolves, a focus on improving measurement techniques will be crucial for advancing effective and personalized behavioral guidance strategies.

This project was supported by Meharry Medical College School of Dentistry

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NONPHARMACOLOGIC BEHAVIOR GUIDANCE IN THE HEALTHY CHILD COMPARED TO THE CHILD WITH SPECIAL HEALTH CARE NEEDS: A LITERATURE REVIEW

Blair Jason, Aryagne Dos Santos, Micah Armstrong, Lauren Jordan, Jalen Sims, Lauren Waller and Mirissa Price

School of Dentistry, Department of Pediatric Dentistry, Meharry Medical College, Nashville, TN

Odontophobia and dental fear and anxiety (DFA) are terms used to describe the fear of dental treatment, with signs of terror, hypertension and unease as specified in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV. Estimated prevalence of DFA for children is 9%, with that prevalence being greater among children with special health care needs (SHCN). Basic behavioral guidance techniques, such as tell-show-do and distraction, are often highly effective in the typically developing child. However, more advanced interventions may be necessary for a child with SHCN.

A literature search was performed for keywords of “pediatric dental anxiety,” “behavior management,” “distraction methods,” “non-pharmacological methods,” and “special health care needs in Science Direct, PubMed, ClinicalKey and EBSCO. Articles (n=25) from 2014 to 2024 pertaining to patients aged 4 to 18 and mentioning distraction as a behavior guidance tool in a dental setting were included.

Active distraction methods significantly reduce anxiety in children during dental procedures. The combination of tellshow-do and audio-visual techniques with other methods is particularly effective with typically developing children. Children with SHCN, however, have more significant response to greater stimulation, such as audio-visual techniques, and advanced techniques, such as passive restraint. Parents of children with SHCN are more likely to accept such advance techniques.

Distraction-based, non-pharmacologic behavior management strategies are an effective tool to enhance patient outcomes in a pediatric setting. However, additional tools may be necessary and should be taught in dental school and continuing education to improve access to effective care for children with SHCN.

This project was supported by Meharry Medical College School of Dentistry.

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PORPHYROMONAS GINGIVALIS DERIVED LIPOPOLYSACCHARIDE UPREGULATES INSULIN SECRETION FROM PANCREATIC Β CELL LINE MIN6

Chethan Sampath, Pandu Gangula

Department of ODS & Research, Meharry Medical College School of Dentistry, Nashville, TN 37208

A bidirectional relationship between periodontitis and diabetes has been demonstrated in human cross-sectional studies, but the mechanism between these two conditions is not completely understood. Porphyromonas gingivalis (Pg, a major periodontal pathogen) is noted to be significantly higher in patients with periodontitis (PD). Endotoxins released from periodontal pathogens such as lipopolysaccharide (LPS) by Pg plays an important role in the pathogenesis of periodontitis. We hypothesized that Pg-LPS may stimulate insulin secretion directly effecting β cell function. To test this hypothesis, pancreatic β cell line MIN6 cells were used to determine the effect of LPS derived from Pg on insulin secretion. Furthermore, expression of genes altered by Pg-LPS in innate immunity and insulin-signaling pathways was determined.

MIN6 cells were grown in medium with glucose concentration of normoglycemia (5.5 mM). Pg-LPS was added to each well at final concentrations of 10, and 100 ng/mL respectively. Insulin secretion was measured using enzyme-linked immunosorbent assay. Gene expression levels altered by Pg-LPS were determined by polymerase chain reaction (PCR) for specific genes of interest by quantitative PCR. Statistical analysis was performed using one way ANOVA. Mean ± SD, p<0.05 considered as significant.

Pg-LPS stimulated insulin secretion in the normoglycemic condition by ≈1.5- to 3.0-fold depending on the concentration of LPS. Pg-LPS treatment altered the expression of several genes involved in innate and adaptive immune response and insulin-signaling pathway. Pg-LPS upregulated the expression of the immune response–related genes cluster of differentiation 8a (Cd8a), Cd14, and intercellular adhesion molecule-1 (Icam1) by about two-fold. LPS also increased the expression of two insulin signaling–related genes, glucose-6-phosphatase catalytic subunit (G6pc) and insulin-like 3 (Insl3), by three- to four-fold.

In summary, we have demonstrated that Pg LPS stimulates insulin secretion by pancreatic β cell line MIN6 cells. Pg LPS may have significant implications on the development of β cell compensation and insulin resistance in prediabetes in individuals with periodontitis.

We would like to acknowledge funding from the National Institute of Dental and Craniofacial Research (NIDCR, U01DE033241, PG); National Institute of General Medical Sciences (NIGMS, R16GM149440, PG); National Institute on Minority Health and Health Disparities (NIMHD, UC2MD019626, Drs. PG, Lindsey and Cheairs)

Oral SOD-6

MACHINE LEARNING-BASED ANALYSIS OF DEMOGRAPHIC AND BEHAVIORAL FACTORS INFLUENCING DENTAL HEALTH OUTCOMES

Ciarra C Collins1, Mariam G Hawaz1, Alyse A Pearson-Bryant1, Tina K Tran1, Onyeka Oguagha1, Ryan N, Elliott1, Cherrelle D Perkins1, Erika L Taylor1, Nicole Martes Fernandez1, Azizat Adediran1, Dollada Srisai1, Glory Stanton2, Anaite Montes Bu2, Chen Chau-Kuang3, Tiffany Wilson4, Semi Zouiouich5, AmandaHoffman5, Claudia Montes5, Ashley Sauer5, Natalia Wadsworth5, Casey L. Dagnall5, Jianxin Shi5, Alexys Ferguson1, James Cade1*, Khoury Zaid1*, Emily Vogtmann5*, Pandu Gangula1*

*These authors contributed equally

1Department of Oral Diagnostic Sciences & Research, School of Dentistry, Meharry Medical College, Nashville, TN

2Department of Internal Medicine, School of Medicine, Meharry Medical College, Nashville, TN

3School of Graduate Studies, Meharry Medical College, Nashville, TN

4Department of Public Health, Meharry Medical College, Nashville, TN

5Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD

This study evaluates the impact of demographic and behavioral factors on prevalent dental health conditions using machine learning models. The objective is to identify key predictors such as age, socioeconomic status, smoking, and drinking habits that influence oral health in underserved populations.

This study was approved by the Institutional Review Board at Meharry Medical College (#22-12-1265). Sixty-one participants, aged 30 to 70, were enrolled at the School of Dentistry. Data were collected via electronic surveys (REDCap) on

demographics and behaviors, such as smoking and alcohol consumption. Dental health was assessed using two methods: counting teeth with caries or restorations (0–17, mean ± SD: 6.9 ± 4.6), analyzed using linear regression to identify predictors; and classifying health as poor if fewer than 20 sound teeth were present, with Random Forest and XGBoost models identifying key predictors. An 80–20% training-validation split was used for analysis.

Most participants (68.9%) identified as Black, 21.3% as White, and 5.0% as Hispanic. In linear regression, cigarette use was the strongest predictor of increased caries (p = 0.025), followed by sex when analyzing the factors contributing to an increased number of carious teeth. Random Forests identified age, education, sex, and vape use as key factors, with age having the highest importance (14.615). XGBoost showed age as the top predictor, with education and alcohol consumption also significant. Mean Squared Error indicated good model calibration.

The study’s conclusions emphasize that demographic and behavioral factors, particularly age, education, and smoking habits, play crucial roles as determinants of dental health in underserved populations. Based on these findings, the researchers advocate for the development of targeted interventions to address these modifiable risk factors within underserved communities.

This study is supported by NCI (Dr. Vogtmann) and HRSA-COE grant (D34HP00002) funded by the School of Dentistry, Meharry Medical College.

THE IMPACT OF AGE, HUMAN IMMUNODEFICIENCY VIRUS INFECTION (HIV-I) AND HEALTH STATUS ON SALIVA FLOW RATE IN DENTAL PATIENTS

Dollada Srisai1, Aerial Griffin1, Gunaraj Dhungana1, Chethan Sampath1, Ethel Harris2, Leela Subhashini Alluri3, Vladimir Berthaud2, David Mott3, James Cade1, Alexys Ferguson1, Anaite Montes Bu5, Derek Wilus4, Mohammad Tabatabai4, Zaid Khoury1, Cherae Farmer-Dixon1, Pandu R Gangula1

1Department of Oral Diagnostic Sciences & Research, School of Dentistry, Meharry Medical College, Nashville, TN

2Department of Internal Medicine, Meharry Community Wellness Center, School of Medicine, Meharry Medical College, Nashville, TN

3Department of Periodontology, School of Dentistry, Meharry Medical College, Nashville, TN, USA, 37208

4School of Global Health, Meharry Medical College, Nashville, TN

5Center for Women’s Health Research, School of Medicine, Meharry Medical College, Nashville, TN

Saliva flow rate is a critical indicator of oral health, influenced by various systemic conditions. This study aims to assess the association between saliva flow rate, HIV-I status, and periodontal disease, as well as evaluate the impact of other health factors such as age, behavioral risks, and a history of systemic diseases.

This study was approved by the Institutional Review Board at Meharry Medical College (#22-12-1265). Associations between saliva flow rate, HIV status, periodontal disease (PD), and other health factors were investigated in a total of 153 participants, divided into four groups: HIV-negative without PD (n = 63), HIV-negative with PD (n = 43), HIV-positive without PD (n = 20), and HIV-positive with PD (n = 27). The racial distribution among participants was as follows: Black (67.32%), White (19.6%), Asian (5.88%), Hispanic (2.61%), and individuals identifying as two or more races (4.57%). The Shapiro-Wilk test was used to assess normality, while the Kruskal-Wallis test, followed by Dunn’s multiple comparisons test, was employed to evaluate differences across groups. Additionally, the Mann-Whitney U test was used to analyze associations between saliva flow rate, HIV status, and other health factors.

HIV-negative individuals without PD had significantly higher saliva flow rates compared to both HIV-positive groups (p < 0.05). The Mann-Whitney U test further confirmed that HIV-positive individuals had lower saliva flow rates than HIV-negative individuals (U = 3576.5, p < 0.001). Age was negatively correlated with saliva flow rate, showing a significant decline in older participants. However, PD severity was not significantly associated with saliva flow rate. Among other health predictors, a history of sexually transmitted diseases (p = 0.03) was significantly associated with lower saliva flow rates, while diabetes, hypertension, and smoking showed no significant effects.

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In summary, age, sexually transmitted diseases and HIV infection reduced the salivary flow rate compared to other factors examined in this study.

We thank 408 predoctoral students for participating in clinical research rotations each week administering oral and dental health surveys and collecting oral specimens. We also thank Dr. Anita Sykes-Smith, clinical faculty and all others including staff Ms. Yarbrough, Ms. Goodbar, Mr. Byers and his team for their assistance. This research was partly supported by the 1) National Institute of Dental and Craniofacial Research (NIDCR), USA, Grant (U01DE033241, PG); 2) HRSA-COE Grant (D34HP00002) (support dental student research) to School of Dentistry;; 3) National Institute of General Medical Sciences (NIGMS), USA, Grant (R16GM149440, PG); 4) National Institute on Minority Health and Health Disparities (NIMHD), USA, Grant (UC2MD019626, PG, Drs. Lindsey and Cheairs) and 5) American Cancer Society (ACS), Diversity in Cancer Research Institutional Development Grant (DICRIDG2107101, Dr. Adunyah). Biostatistics Core was partly funded by RCMI (MD007586). HRSA grant award H76UA01706; NIH/NIAID grant award P30 AI110527, TN-CFAR.

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THE EFFECT OF INTERGENERATIONAL DENTAL ANXIETY ON CHILDREN’S ORAL HEALTH AND BEHAVIOR

D. Gilmore, F. White, N. Tombo, A. Cumberlander, D. Lyons, J. Carter, K. Harris, F. Patel, R. Kiran, A. M. Yacoub, N. Mossad, G. Akunna, D. Martin, J. Zirker, C. McGee, M. Amin, M. Fanous

School of Dentistry, Meharry Medical College, Nashville, TN 372208

Dental fear and anxiety are prevalent concerns in clinical practice, often leading to the avoidance of routine dental care. Pre-appointment anxiety can significantly impact patients of all ages, resulting in delayed treatment and increased oral health complications. Research suggests that parental dental anxiety plays a pivotal role in shaping children’s perceptions of dental visits. Children of parents with dental-related fears are likely to develop similar anxieties, which contribute to long-term oral health neglect. Understanding this intergenerational influence is critical in developing effective interventions to promote positive dental experiences.

The objective of this case study is to examine the impact of parental dental anxiety on a child’s oral health and behavior, emphasizing the need for early intervention. This case report deals with a 16-year-old Hispanic female with no significant medical history presented with complaints of dental discomfort. The patient’s mother reported that her last dental visit occurred seven years ago. The patient expressed a strong aversion to dental care, citing her parents’ similar apprehensions as a primary reason for avoiding treatment. Clinical examination revealed a high caries risk and generalized gingivitis, indicative of prolonged neglect of oral hygiene and preventive care.

Dental anxiety, whether in children or adults, remains a significant barrier to optimal oral health. This case underscores the critical role of parental influence in the development of dental fear and subsequent oral health neglect. Despite advancements in pain management and minimally invasive dental procedures, high levels of dental anxiety persist among both children and parents. Addressing this issue requires a multidisciplinary approach, incorporating early exposure to positive dental experiences, behavioral counseling, and targeted patient education. Parental involvement is essential in shaping children’s attitudes toward dental care, highlighting the necessity of educating caregivers on the importance of regular dental visits and preventive measures. Future research should focus on identifying effective strategies to mitigate dental anxiety across generations, ensuring improved long-term oral health outcomes.

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UNCHARACTERISTIC PRESENTATION OF A RARE DISEASE IN A PATIENT WITH SPECIAL HEALTHCARE NEEDS: SCURVY

Melissa D. Porter1, Micheal Curry2, Jada Pierre2, Kristin Smith2 , Dwight Martin2, Lark Taylor2, Mirissa Price3, Zaid Khoury4

1Department of Pediatric Dentistry, Pediatric Residency Program, School of Dentistry, Meharry Medical College, Nashville, TN.

2School of Dentistry, Meharry Medical College

3Department of Pediatric Dentistry, School of Dentistry, Meharry Medical College

4Department of Oral Diagnostic Sciences & Research, School of Dentistry, Meharry Medical College

Vitamin C, an essential nutrient, is crucial in collagen synthesis, immune function, and antioxidant defense. Severely insufficient levels of vitamin C can disrupt these processes, resulting in scurvy—a condition characterized by compromised collagen production and tissue degradation. This case report describes a complex case of a pediatric patient exhibiting oral lesions of unknown etiology. Biopsy confirmed granulomatous lesions in the presence of a Vitamin C deficiency and an ultimate diagnosis of exclusion: scurvy. In the United States, scurvy is rare in all but patients with underlying conditions and restrictive diets. Scurvy typically presents with oral manifestations such as gingival swelling, bleeding, petechiae, and systemic symptoms like fatigue, irritability, and joint pain. In pediatric populations, these symptoms can significantly impact the quality of life and, if untreated, lead to severe complications affecting life expectancy. Understanding the relationship between vitamin C deficiency and its clinical manifestations is crucial for accurate diagnosis and effective management.

DYSREGULATION OF SALIVARY BIOMARKERS IN PERSONS LIVING WITH HIV INFECTION AND PERIODONTAL DISEASE

Gunaraj Dhungana1, Dollada Srisai1, Chethan Sampath1, Ethel Harris2, Leela Subhashini Alluri3, Vladimir Berthaud2, David Mott3, James Cade1, Alexys Ferguson1, Anaite Montes Bu5, Derek Wilus4, Mohammad Tabatabai4, Zaid Khoury1, Cherae Farmer-Dixon1, Pandu R Gangula1

1Department of Oral Diagnostic Sciences & Research, 3Department of Periodontology, School of Dentistry, Meharry Medical College, Nashville, TN

2Department of Internal Medicine, Meharry Community Wellness Center, School of Medicine, Meharry Medical College, Nashville, TN

3Department of Periodontology, School of Dentistry, Meharry Medical College, Nashville, TN, USA, 37208

4School of Global Health, Meharry Medical College, Nashville, TN

5Center for Women’s Health Research, School of Medicine, Meharry Medical College, Nashville, TN

Periodontal disease (PD) is primarily driven by the immune response to polymicrobial communities, particularly the Red Complex bacteria in dental biofilm. Persons living with HIV (PLWH) are at a higher risk for severe PD, with prevalence rates reaching 62% in the U.S. and up to 75% globally. Notably, however, salivary biomarkers in PLWH with or without PD remains underexplored in underserved population. The objective of this study is to assess alterations in immune response in periodontitis in persons living with or without HIV infection.

Informed consent was obtained from all participants upon Institutional Review Board approval from Meharry Medical College. Following inclusion and exclusion criteria, participants were divided into four groups: Group 1 (HIV-PD-, n=19), Group 2 (HIV−PD+), n=15), Group 3 (HIV+PD-), n=12), and Group 4 (HIV+PD+), n=13). Unstimulated saliva was analyzed for 96 biomarkers, including cytokines, chemokines, and growth factors, using Luminex xMAP technology. Statistical analysis was done using the Kruskal-Walli’s test (p<0.05). Data are presented as Mean ± SD.

Salivary cytokine profiling revealed distinct immune responses across the four groups, with a significant alteration (p < 0.05) in 12 biomarkers (G-CSF, GROα, IL-5, IL-18, MDC, RANTES, TNFα, APRIL, Granzyme B, MIP-3α, sCD137, and sFasL), indicating differential immune activation in PLWH with or without PD. Correlation analysis demonstrated distinct salivary cytokine levels with advancing periodontitis. Interestingly, the HIV−PD+ group exhibited a greater number of significant cytokines and stronger correlations, suggesting a more pronounced immune response compared to the HIV+PD+ group. Principal component analysis (PCA) further highlighted distinct cytokine signatures, with the HIV+PD+ group displaying immune dysregulation driven by the combined effects of HIV-associated immunosuppression and periodontal inflammation.

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These findings underscore the impact of HIV-induced immunosuppression on periodontal disease progression, highlighting the potential of salivary cytokine profiling as a biomarker for disease monitoring and immune dysregulation assessment.

We thank 170 predoctoral students for participating in clinical research rotations each week and working with patients in collecting oral and dental health surveys, and oral specimens including saliva. We also thank clinical faculty Dr. Anita Sykes-Smith and all others including staff Ms. Yarbrough, Ms. Goodbar, Mr. Byers and his team for their help and support. Dental student research is supported by the HRSA-COE funding (D34HP00002) to the School of Dentistry, Meharry Medical College, and Nashville, Tennessee. NIH- Research reported in this presentation was supported by the National Institute of Dental & Craniofacial Research under award number U01DE033241 (Pandu Gangula) and National Institute of General Medical Sciences under award number R16GM149440 (Pandu Gangula), and National Institute on Minority Health and Health Disparities (NIMHD), USA, Grant (UC2MD019626, PG, Drs. Lindsey and Chearis).

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RARE AND EXTENSIVE MALIGNANT MELANOMA OF THE ORAL CAVITY: REPORT OF ONE CASE

Shirin Shahnaseri1,2, Ihunna Amugo2

1Department of Oral & Maxillofacial Surgery, School of Dentistry, Meharry Medical College, Nashville, TN, USA.

2School of Dentistry, Isfahan University of Medical Sciences, Isfahan, IRAN.

Cutaneous and mucosal melanomas are arising from malignant transformation of melanocytes. Mucosal Melanoma (MM) is a rare form of melanoma with anaggressive clinico-pathological behavior and poor prog-nosis with a 5-year survival rate of <25%. Mucosal Melanomas (MMs) are most often found in the upper aerodigestive tract (mouth, pharynx, larynx, nasal cavity, paranasal sinuses, and salivary glands), the genito-urinary tract and the anorectal region. Approximately 55% of all MMs begin in the head and neck region. Furthermore, 70% of MMs of the head and neck are in the nasal cavity and paranasal sinuses, but only 25% occurred in oral mucosa. The incidence of primary oral melanoma (OMs) is varying broadly between 0.2-0.8% of all melanomas and 1.3% of all cancers and 0.5% of all oral malignant neoplasms. Primary malignant melanoma of the oral cavity is a rare type of melanoma. In contrast to cutaneous melanoma, MMs have an unknown etiology, because the affected sites of the lesion are not exposed to solar radiation. The most common location of oral melanomas is the maxillary gingiva, hard palate, and alveolar ridge; only 20% of theses lesions are observed in the mandibular mucosa. Oral melanomas are usually asymptomatic with irregular shape and dark brown to block color. The lesion is often detected by significant swelling, tooth mobility, ulceration, or hemorrhage of the overlying epithelium. Immunohistochemical staining with antibodies against certain melanocytic differentiation antigens is always required for confirmation of the diagnosis of amelanotic melanoma. Most OMs have aggressive biological behavior and show high incidence of metastasis, recurrence and death. This report presents clinical, histopathological, and immunohistochemical features of one case with an advanced oral melanoma: one pigmented melanoma in a 46-year-old female patient.

Dental student research is supported by the HRSA-COE funding (D34HP00002) to the School of Dentistry, Meharry Medical College.

Poster SOD-12

COMPARISON OF EFFICACY OF CCLAD DELIVERY SYSTEM VERSUS TRADITIONAL LOCAL ANESTHESIA ADMINISTRATION TECHNIQUE

Jadyn Lewis

School of Dentistry, Meharry Medical College, Nashville, TN 37208

This review evaluated and compared the effect of a computer-controlled local anesthetic delivery system (CCLAD) and traditional local anesthetic techniques via a syringe. With recent advancements in local anesthesia techniques in den-

tistry, these three studies assess pain reduction and patient comfort using different administration techniques. The first study explores the effect of needle insertion angles on pain perception during labial infiltration anesthesia, revealing that a modified angle and computer-controlled local anesthetic delivery (CCLAD) significantly decrease discomfort. The following study evaluates the efficacy of CCLAD systems compared to traditional syringe injections, demonstrating that computer-controlled anesthesia results in lower pain perception and improved patient cooperation, particularly in pediatric and anxious adult patients. Lastly, the third study focuses on the SleeperOne S4, a CCLAD system, highlighting its effectiveness in reducing injection-related pain in children. The findings suggest that CCLAD significantly lowers discomfort compared to manual syringe injections. Collectively, these research studies reinforce the growing role of computer-assisted anesthetic systems in modern dentistry, offering a promising approach to improving patient experience and reducing dental anxiety. Further research is recommended to explore the long-term impact of these innovations on clinical practices.

Poster SOD-13

EVALUATING THE STANDARD-OF-CARE BEHAVIOR MANAGEMENT PRACTICES IN THE MEHARRY MEDICAL COLLEGE PEDIATRIC DENTAL CLINICS: THE EFFECT OF PHYSICAL DISTRACTION ON PEAK HEAT RATE AND FRANKL SCORE OF PEDIATRIC DENTAL PATIENTS DURING HAND SCALING.

Department of Pediatric Dentistry, School of Dentistry, Meharry Medical College, Nashville, TN

Pediatric dental anxiety can result in treatment avoidance, compromised oral health, and increased challenges for dental professionals. Non-pharmacological behavior guidance techniques, including physical distraction, offer cost-effective and low-risk interventions to manage patient anxiety. The aim of this mixed-methods clinical study is to evaluate the impact of physical distraction, specifically therapeutic toys/stress balls, on managing pediatric anxiety in the dental setting. Participants (n=66) aged 4 to 14 received hand-scaling of anterior teeth both with and without the stress ball intervention. Patients were randomly assigned to groups such that half of patients received the stress ball as the first intervention, and half received the control of no stress ball as the first intervention. Tell-show-do was used, as well, for all patients and groups. Heart rate and Frankl score were reported by calibrated examiners.

A majority of patients (92%) had parent-reported dental anxiety, with 1 patient also having a diagnosis of ADHD and 4 having a dual-parent-reported diagnosis of autism spectrum disorder. 50% of patients were female, and 49% spoke Spanish as a primary language. 97% of patients had a high Caries Risk Assessment (CRA) with only 2 patients having a Moderate CRA. Paired Samples T-Test showed use of the stress ball had a large effect (d=5.3, P< .05) on heart rate and medium effect (d=0.52, P< 0.05) on Frankl score.

In summary, the use of a stress ball in combination with tell-show-do results in significant reduction in heart rate and improvement in Frankl score for pediatric patients in the dental setting.

Poster SOD-14

PATIENT FACTORS ASSOCIATED WITH PREVENTIVE VERSUS RESTORATIVE DENTAL APPOINTMENT ATTENDANCE IN AN URBAN EDUCATIONAL CENTER: A 10-YEAR RETROSPECTIVE CHART REVIEW

Joshua Delaney, Tamera Thomas, Mirissa Price

Department of Pediatric Dentistry, School of Dentistry, Meharry Medical College, Nashville, TN

Every missed pediatric dental appointment represents a missed opportunity to deliver dental care, with potential consequences for oral health and overall well-being. Several factors have been identified as associated with missed health care appointments including oral health literacy, time constraints, and self-regulation. This study aims to determine whether there is a correlation between establishment of a treatment plan and patient retention for preventive and/or restorative appointments. This study further explores the role of gender, ethnicity and SES on appointment attendance. A retrospec-

Aryagne Dos Santos, Micah Armstrong, Blair Jason, Lauren Jordan, Jalen Sims, Lauren Waller and Mirissa Price

tive chart review was conducted of the predoctoral pediatric dental clinic at Meharry Medical College from 2013 to 2023. ANOVA analysis and a two-sided t-test were used for analysis. The subjects aged 0-17, encompassing boys and girls of various ethnicities, were included in analysis. Patient attendance at the second appointment positively correlated to dental pain and to a restorative treatment plan (p<0.05); however, there was no significant correlation with completion of care. Pediatric dental patients are more likely to attend appointments when they have pain or when treatment is indicated; however, attendance drops off after the second appointment in all cases. This study highlights the importance of patient education on the importance of all phases of treatment, including prevention. Without support of oral health literacy, efforts to establish dental homes for pediatric patients will remain limited.

Dental student research is supported by the HRSA-COE funding (D34HP00002) to the School of Dentistry, Meharry Medical College.

Poster SOD-15

EXAMINING ORTHODONTIC REFERRAL PATTERNS OF PEDIATRIC DENTISTS: A SURVEY STUDY

Monica L. Bean, a* Kandyce R. Kirt,a* Mirissa D. Price, *Denotes Equal Contribution

School of Dentistry, Meharry Medical College, Nashville, TN

General Dentist Practitioners (GDPs) play an essential role in the process of orthodontic referral. An inadequate referral, however, can result in lost time, confusion, failure of the patient to see the referral through, and even malpractice claims. To assess the factors or information which make up a successful orthodontic referral, as well as the success of orthodontic referral patterns, a survey study was conducted based on the criteria of the American Academy of Pediatric Dentistry (AAPD).

A REDCap survey was distributed via email to all registered pediatric dentists in the Southeastern district according to the AAPD listserve (n=1537). Survey responses (n=74) were evaluated using descriptive statistics and multivariate logistic regression.

While board certified pediatric dentists are more likely to refer to an orthodontist based on esthetics (B=1.473, p<0.05), non-board-certified pediatric dentists were more likely to include patient demographics (B=-1.605) and request for care updates in their referral (B=-1.473, P<0.05). Less seasoned dentists are more likely to consider orthodontists’ availability (B=-0.662) and the ability for financial accommodation (B=-0.662) when referring.

Our results indicate that continuing education and training specifically to orthodontic referrals is necessary to support successful patient referrals to orthodontic care.

Poster SOD-16

MOLAR-INCISOR HYPOMINERALIZATION AS AN UNDERSTUDIED DEVELOPMENTAL DISORDER: ETIOLOGY, DIAGNOSIS, AND PREVALENCE RATES IN THE UNITED STATES

Montana Joseph-Schelchere1, Jelani Williams1, Chelsea Appiah1, Huthayfah Walker1, Safa Khan1, Markez Coleman1 , Cherae Farmer1, Ethel Harris2

1School of Dentistry, Meharry Medical College, Nashville TN

2Department of Internal Medicine, Meharry Community Wellness Center, School of Medicine, Meharry Medical College, Nashville, TN

Molar-incisor hypomineralization is increasingly recognized as a developmental disease with understudied prevalence in the United States. MIH is a qualitative enamel defect: associated with difficulty in achieving anesthesia, crown fracturing during normal masticatory action, development of carious lesions at demarcated enamel margins, and other complica-

tions that adversely affect oral health. These effects pose difficulties in the clinical management of MIH and can lead to heightened dental anxiety and avoidance in those diagnosed. Current research supports an estimated prevalence of 9.6% - 13%. While the rates of MIH occurrence across different races and ethnicities have been reported as equal, there is little research into whether individuals diagnosed with MIH are more prone to caries, tooth loss, and other dental complications depending on their race and/or ethnicity. We critically reviewed current literature and data on MIH in the context of prevalence, etiology, diagnosis and potential differences in the severity rates in different racial and socioeconomic populations within the United States. Our research design involves analyzing current peer-reviewed literature of MIH patient populations to identify if racial minority patients have an increased rate of dental caries, edentulism, and fracturing of permanent first molars and incisors compared to those of ethnic and racial majorities. Electronic databases used include National Library of Medicine, Science Direct, and Google Scholar with databases limited to 2018 –2024. Although MIH has the same prevalence across all races, those who are of racial and ethnic minorities may have increased dental issues; lack of oral health resources, cultural practices that may not emphasize dental hygiene health and lowered personal perceptions of the health status of their teeth. In understanding how an MIH diagnosis can disproportionately affect those of racial minorities, we can seek to improve treatment options and provider care for patients presenting with MIH. Dental student research is supported by the HRSA-COE funding (D34HP00002) to the School of Dentistry, Meharry Medical College, and Nashville, Tennessee.

Poster SOD-17

CASE REPORT: SUSPICION OF SUBMUCOSAL CLEFT IN A PEDIATRIC PATIENT

Nicole Martes-Fernandez, Cherrelle Perkins, Karmen Jones, Dr. Keisha Brady, DDS, Dr. Mirissa Price, DMD

School of Dentistry, Meharry Medical College, Nashville, TN 37208

Submucosal cleft palate (SMCP) is a rare congenital condition caused by improper fusion of the soft palate muscles during fetal development. It is typically diagnosed later in life, often between 4 and 5 years of age, and can present with dental anomalies similar to those seen in more severe cleft conditions. Treatment is generally recommended only for symptomatic cases with velopharyngeal insufficiency, with a “butterfly-suture” veloplasty showing effectiveness for those needing surgery. This case report highlights a pediatric patient with suspected SMCP resulting in orthodontic anomalies.

A 9-year-old African American male with medical history significant for asthma presented to the Meharry Pediatric Dental Clinic in Nashville, TN, for a comprehensive oral evaluation with his father in July 2024. Chief complaint was the appearance of the maxillary incisors, and pain of the mandibular molars. Intraoral exam was significant for a bifid uvula, and a Mallampati and Brodsky score of 3. The maxilla had severe crowding with megalodontia of #8, supernumerary #10’, and rotated #7 and #10. The patient was referred to a Craniofacial Orthodontist with differential of submucosal cleft lip and palate.

Cases of submucosal cleft palate (SMCP) often go undetected prior to eruption of primary and permanent teeth. SMCP can be suspected in patients with a bifid uvula in combination with dental anomalies. The complexity of such cases requires a team-based approach, including a craniofacial orthodontist. Timely diagnosis and intervention are essential to manage both the dental issues and functional impairments associated with SMCP, ensuring the best possible outcome for the patient.

Poster SOD-18

CORRELATION OF ORAL HEALTH LITERACY AND ORAL HEALTH BEHAVIORS IN CHILDREN

AGED 13-17 YEARS OLD - A LITERATURE REVIEW

Jodine Seide, Keisha Brady, Mirissa Price, Chau-Kuan Chen, Ryan Elliott, Niquia McKenzie, Nicole Martes Fernandez, Mickayla Jasmin, Tiffany Wilson

Department of Pediatric Dentistry, School of Dentistry, Meharry Medical College, Nashville, TN

This literature review aimed to evaluate the correlation between oral health literacy and oral health behaviors in children, adolescents and their caregivers. This study further aimed to identify interventions that increase oral health literacy and positive oral health behaviors in this population. Electronic searches were conducted on oral health literacy and behaviors in children, adolescents, and caregivers in Pubmed, Clinical Key, and ScienceDirect. Search terms collected were based on the population (< 17 years), intervention (oral health literacy tools), comparison (oral health literacy-to-behaviors) and outcomes (e.g. DMFT). Of 50 articles, 32 met criteria for inclusion in the review. Studies show that higher REALD-30 scores are linked to better oral health outcomes, while lower scores are associated with poorer health conditions and inadequate knowledge. Many articles highlight the influence of socioeconomic status (SES) on oral health literacy, with lower SES often correlating with reduced literacy and poorer oral health. Urvashi et. al reported that dental caries was prevalent in 73.2% of cases in the lower middle class, with an inverse relationship between caries and socioeconomic status. Additionally, parental oral health literacy significantly impacts children’s dental health, with higher parental literacy leading to better oral hygiene practices and fewer dental issues in children. Higher REALD-30 scores are associated with improved oral health outcomes. These outcomes include frequent dental visits, adherence to better oral hygiene practices, and reductions in negative oral health behaviors that typically contribute to overall poor oral health. These results support further study into the role of health education intervention on pediatric oral health outcomes.

We thank Pediatric Residency Program at the School of Dentistry, Meharry Medical College.

Poster SOD-18

ASSOCIATION OF ORAL HEALTH BEHAVIOR IN PERSONS LIVING WITH HUMAN IMMUNODEFICIENCY VIRUS AND PERIODONTAL DISEASE

Nnamdi Anige1, Jemila Darling1, Peter Kalu1, Ethel Harris2, Leela Subhashini Alluri3, Vladimir Berthaud2, David Mott3 , James Cade1, Dollada Srisai1, Gunaraj Dhungana1, Alexys Ferguson1, Cherae Farmer-Dixon1, Derek Wilus4, Mohammad Tabatabai4, Zaid Khoury1, Pandu R Gangula1

1Department of Oral Diagnostic Sciences & Research, 3Department of Periodontology, School of Dentistry, Meharry Medical College, Nashville, TN

2Department of Internal Medicine, Meharry Community Wellness Center, School of Medicine, Meharry Medical College, Nashville, TN

4School of Global Health, Meharry Medical College, Nashville, TN

Persons living with HIV (PLWH) are particularly susceptible to severe forms of periodontal disease (PD), with an incidence of up to 66%. This study investigates the association between oral health behaviors and periodontal disease among PLWH. This study enrolled 58 participants aged 18 years and above, divided into four groups: Group 1 (HIV- and PD-), Group 2 (HIV- and PD+), Group 3 (HIV+ and PD-), and Group 4 (HIV+ and PD+). Predoctoral dental students administered surveys assessing oral health behaviors. Frequency analysis was performed on all categorical variables. Depending on the frequency of each cell, a Chi-square or Fisher’s exact test was used. In the event that Fisher’s exact test failed, the p-value was computed based on Monte-Carlo simulation. For continuous variables, Kruskal-Wallis was used to determine group differences. R/RStudio version 4.4.1 was used for all analyses. Of the 58 patients, 31 were male and 27 were female, with males predominating in Groups 2-4. Significant associations were identified in several of the oral health and social determinants of health (SDoH) variables among all groups. Educational attainment was significantly higher in Group 1 (p-value < 0.001), with only 6 out of 25 HIV+ completing some college education. Daily flossing was more common among those without PD (71.9%). Among those who lost at least one tooth, 53% were HIV+. There was a significant difference in educational attainment between Groups 1 and 4 (p-value < 0.001) as well as Groups 1 and 3 (p-value < 0.001). The study reveals a strong association between oral health behaviors and the prevalence of PD in PLWH. These findings emphasize the need for enhanced oral health education and accessible dental care for PLWH to prevent PD and improve overall health outcomes.

We thank 170 predoctoral students for participating in clinical research rotations each week administering oral and dental health surveys and collecting oral specimens. We also thank Dr. Anita Sykes-Smith, clinical faculty and all others including staff Ms. Yarbrough, Ms. Goodbar, Mr. Byers and his team for their assistance. Dental student research is supported by the HRSA-COE funding (D34HP00002) to the School of Dentistry, Meharry Medical College, and Nashville, Tennessee.

NIH- Research reported in this presentation was supported by the National Institute of Dental & Craniofacial Research under award number U01DE033241 (Pandu Gangula) and National Institute of General Medical Sciences under award number R16GM149440 (Pandu Gangula). Biostatistics Core was partly funded by RCMI (MD007586). HRSA grant award H76UA01706; NIH/NIAID grant award P30 AI110527, TN-CFAR.

Poster SOD-20

A SMILE IN PERIL – THE BURDEN OF UNTREATED PERIODONTAL DISEASE

Oluwatosin Oluyode, David A. Mott, Pandu R Gangula, Leela Subhashini. C. Alluri2

1Department of Oral Diagnostic Sciences & Research, 3Department of Periodontology, School of Dentistry, Meharry Medical College, Nashville, TN

2Department of Periodontology, School of Dentistry, Meharry Medical College, Nashville, TN, USA, 37208

Periodontal disease is a progressive inflammatory condition that affects the supporting structures of the teeth, often worsened by the buildup of dental calculus. If left untreated, it can lead to irreversible tissue destruction, bone loss, and tooth mobility. This case highlights the consequences of long-term inadequate oral hygiene, delayed dental visits, and lifestyle risk factors in the progression of Generalized Stage 3 Grade B periodontitis.

A 24-year-old Hispanic female presented with concerns about her smile, halitosis (bad breath), and gingival bleeding. She reported a history of irregular oral hygiene practices and had not visited a dentist since childhood. Clinical examination revealed significant supragingival (above the gum line) and subgingival (below the gum line) calculus accumulation, gingival inflammation, periodontal pocketing exceeding 4 mm, and early signs of tooth mobility. Radiographic findings confirmed vertical bone loss and the presence of subgingival calculus. The patient was diagnosed with Stage 3, Grade B periodontitis.

A phased treatment approach was implemented, beginning with scaling and root planing, oral hygiene education, and lifestyle modifications, including counseling to cease vaping. The patient was scheduled for periodontal maintenance at three-month intervals, with a long-term focus on supportive periodontal therapy and management of risk factors. Early intervention showed positive outcomes, improving clinical parameters and addressing psychosocial concerns related to self-esteem and social embarrassment.

This case underscores the importance of early diagnosis and intervention in periodontal disease. Regular dental visits, patient education, and modification of risk factors play a crucial role in preventing disease progression. Comprehensive treatment strategies that address both clinical and patient-centered concerns are essential for achieving optimal oral health outcomes.

This research was partly supported by the 1) National Institute of Dental and Craniofacial Research (NIDCR), USA, Grant (U01DE033241, PG); 2) HRSA-COE Grant (D34HP00002) (support dental student research) to School of Dentistry.

Poster SOD-21

CHANGES IN SALIVA FLOW RATE IN PERSONS LIVING WITH HUMAN IMMUNODEFICIENCY VIRUS AND PERIODONTAL DISEASE: A CLINICAL RESEARCH ROTATION PHASE 1 STUDY

Osrica McLean1, Montana Joseph1, Nmachi Osagiede1, Chelsea Appiah1, Dollada Srisai1, Ethel Harris2, Leela S Alluri3, Zaid Khoury1, Vladimir Berthaud2, David Mott3, James Cade1, Gunaraj Dhungana1, Alexys Ferguson1, Cherae Farmer-Dixon1, Pandu R Gangula1

1Department of Oral Diagnostic Sciences & Research, Department of Periodontology, School of Dentistry, Meharry Medical College, Nashville, TN

2Department of Internal Medicine, Community Wellness Center, School of Medicine, Meharry Medical College, Nashville, TN

Periodontitis (PD) is a chronic inflammatory disease primarily driven by an immune response to polybacterial pathogens, particularly those in the Red Complex of dental biofilm/plaque. Persons living with HIV (PLWH) are at a significantly higher risk of severe PD, with up to 66% affected. Dry mouth or xerostomia occurs when the salivary glands do not produce enough saliva. This study hypothesizes that the saliva flow rate is reduced in PD and PLWH. It aims to explore saliva flow rate differences in PLWH and its relationship with PD. This study was approved by Meharry Medical College’s IRB (IRB23-05-1316). During clinical research rotation, 170 predoctoral dental students collected demographics data and saliva specimens from 59 participants aged 18 year and above, (male, female, all ethnicity background) categorized into four groups: HIV negative without PD (n=20), HIV negative with PD (n=14), HIV positive without PD (n=12), and HIV positive with PD (n=13). Unstimulated saliva samples were collected for five minutes. After brief spinning, saliva volume collected from each patient was measured (mL/min) and noted. Statistical analysis used one-way ANOVA, with significance at p<0.05; Mean ± SD. Most of the participants enrolled in this study were black or African American (77.9%). Saliva flow rate was significantly (P<0.05) lower in HIV positive individuals, with or without PD, compared to healthy controls. Similarly, rates were lower (p<0.05) in HIV positive with PD compared to PD alone group. No significant changes in saliva flow rate were noticed in PD participants. The pilot study indicates a significant reduction in unstimulated saliva flow rate among PLWH with or without PD. This suggests that HIV-related changes in saliva may cause oral microbiome dysbiosis and an increase in proinflammatory biomarkers. Additionally, the harmful bacteria involved in PD may impact salivary gland function and worsen dry mouth (Xerostomia) in PLWH with PD.

We thank 170 predoctoral students for participating in clinical research rotations each week administering oral and dental health surveys and collecting oral specimens including saliva. We also thank clinical faculty Dr. Sykes-Smith and all others including staff Ms. Yarbrough, Ms. Goodbar, Mr. Byers and his team for their assistance. Dental student research is supported by the HRSA-COE funding (D34HP00002) to the School of Dentistry, Meharry Medical College, and Nashville, Tennessee. NIH- Research reported in this presentation was supported by the National Institute of Dental & Craniofacial Research under award number U01DE033241 (Pandu Gangula) and National Institute of General Medical Sciences under award number R16GM149440 (Pandu Gangula).

Poster SOD-22

UNVEILING THE MYSTIQUE OF OIL PULLLING: A LITERARY EXPLORATION OF ITS ROLE AS AN ADJUNCT TO TRADITIONAL

DENTAL THERAPY AND IMPACT ON GINGIVAL HEALTH

Harris2

1School of Dentistry, 2School of Medicine, Meharry Medical College, Nashville TN

It has been reported that up to 90% of the world population suffers from some form of gingival disease with the primary cause being a buildup in bacteria and plaque. Because of this, people are looking for both conventional and unconventional forms of treatment. Oil pulling is an ancient oral hygiene practice with roots in Ayurvedic medicine, dating back thousands of years to ancient India. The practice involves swishing oil, typically sesame oil or coconut oil, in the mouth for about 15-20 minutes and then spitting it out. It is believed to improve oral health by reducing bacteria, plaque, gingival bleeding, and bad breath. While it has gained popularity in recent years as a natural remedy, scientific evidence supporting its effectiveness is limited and further research is needed to fully understand its benefits. In this study, we seek to compare the current literature that includes contemporary data about the effects of oil-pulling on gingival health. In doing this review we hope to extrapolate the findings to add to the limited knowledge about the subject. Methods: To do so, we critically reviewed scientific findings on oil pulling in the United States, literature was retrieved from 2008-2022. Databases used include Google scholar, National Center for Biotechnology and Information (NCBI), and ScienceDirect. With the consensus of the reviewed articles, research suggests that there are benefits in oil pulling in terms of decreasing gingivitis and improving overall oral health. Though not yet approved by the ADA, research suggests notable benefits in reducing oral health issues. If further research is continued, the validity of oil pulling could see its way into being incorporated as a standard of care into dental clinics.

Dental student research is supported by the HRSA-COE funding (D34HP00002) to the School of Dentistry, Meharry

Safa Khan1, Huthayfah Walker1, Markez Coleman1, Chelsea Appiah1, Montana Joseph-Schelchere1, Jelani Williams1 , Cherae Farmer1, Ethel

Medical College, and Nashville, Tennessee

Poster SOD-23

THE EFFECTIVENESS OF CLEAR ALIGNERS FOR CLASS II CORRECTION IN GROWING PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Seyed Amir Mousavi1, Hooman Shafaee2, Mahsa Ghorbani3, Erfan Bardideh3, Shirin Shahnaseri4, Sercan Akyalcin5

1.Endodontics Department, School of Dentistry, Meharry Medical College, Nashville, TN

2.Orthodontics Department, Dental School, Mashhad University of Medical Sciences, Mashhad, Iran.

3.Dental Research Center, Orthodontics Department, Mashhad University of Medical Sciences, Mashhad, Iran.

4.Oral Maxillofacial Surgery Department, School of Dentistry, Meharry Medical College

5.Orthodontics Department, Harvard School of Dental Medicine, Boston, MA

Recent developments in aligner materials have enabled them to be a feasible choice for children and adolescents. Aligners offer a treatment modality for Class II correction in growing patients claiming to address a mandibular deficiency.

The effectiveness of functional aligners in skeletal Class II treatment is assessed through a systematic review and meta-analysis of the existing literature. A comprehensive search was conducted in MEDLINE, Web of Science, EMBASE, Scopus, and Cochrane’s CENTRAL up to April 2024, with no language or date restrictions. The selection criteria include clinical studies that complied with the PICO question model were included, and the ROBINS-I tool was used to assess their risk of bias.

We extracted relevant data from the included studies using customized data forms and pooled the results via a random-effects inverse variance meta-analysis. Different treatment approaches for growth modification, including Twin-Block, were compared to clear aligners. The primary outcomes measured were ANB, SNB, and overjet. Additionally, secondary outcomes included SNA, wits appraisal, mandibular total length, ramal length, angle of convexity, overbite, molar relationship, vertical positions of incisors and molars, incisor angular shifts, interincisal angle, gonial angle, mandibular plane angle, lower anterior facial height, as well as soft tissue changes, such as the distance of the lips from the E-line.

In our analysis of 21 studies evaluating the treatment outcomes of functional aligners for growing skeletal Class II patients, we observed significant reductions (P<0.05) in ANB, Wits appraisal, angle of convexity, overbite, overjet, molar relationship, maxillary incisor angle. In addition, we found that SNB, mandibular incisor angle (IMPA), mandibular incisor horizontal position, mandibular molar vertical position, interincisal angle (L1-U1), mandibular total length, mandibular base length, ramal length, and lower anterior facial height all exhibited a significant increase (P<0.05). Thirteen of the included studies indicated no significant treatment difference between functional aligners and other functional appliances except for mandibular plane angle, lower incisor horizontal position, interincisal angle, and ramal length.

The findings show that aligners might be a viable option in addressing mild to moderate skeletal Class II malocclusions of growing patients. Compared to other functional appliances, there were no treatment differences in most parameters studied. Based on limited evidence, our results should be interpreted with caution and evaluated with further high-quality studies with long-term observation.

Poster SOD-24

EFFECTS OF MUSIC AND AROMA THERAPY ON ANXIETY OF ENDODONTICS PATIENTS: A RANDOMIZED CLINICAL TRIAL

Seyed Amir Mousavi

Department of Endodontics, School of Dentistry, Meharry Medical College, Nashville, TN

Music and aroma have been known as non-invasive relaxing treatments. Endodontic treatment is considered a distress-

ing treatment in dental offices. This study aimed to find the effect of these non-invasive interventions on the anxiety of patients receiving root canal treatment.

In this single-blinded parallel superiority randomized clinical trial, 72 adult patients who were diagnosed with irreversible pulpitis and normal periapical condition, referred to Dental School for endodontic treatment, were divided into 4 groups randomly: the control group, the music group (Stefano Crespan Shantam, adjusted on 432 Hz), the aroma group (5 drops of lavender odor in humidifier), the music and aroma group. The blood pressure and heart rate were evaluated in each group before and after intervention. The data were analyzed using SPSS software and One-Way ANOVA.

Although there was a decrease in the systolic and diastolic blood pressure and heart rate of the intervention groups after treatment, there was no statistically significant difference compared to the control groups (P > 0.05, One-Way ANOVA). Music and aroma have no effect on reducing the anxiety of endodontic patients and other techniques should be applied by clinicians to manage the anxiety of patients.

Poster SOD-25

COMPARING COMPOSITE AND AMALGAM FILLINGS FOR POSTERIOR TEETH: A LITERAL ANALYSIS

WEIGHING THE BEST OPTIONS

Shania

Ferguson1, Kianna Martin1, Ethel Harris2

1School of Dentistry, Meharry Medical College, Nashville TN

2Department of Internal Medicine, Meharry Community Wellness Center, School of Medicine, Meharry Medical College

Dental caries is one of the most common infectious microbiologic diseases in humans. Standard treatment includes removing decayed tooth tissue and restoring the cavity with filling material. The most used filling materials for dental restorations are composite resin and amalgam. Amalgam is an alloy made by mixing mercury with silver, tin, and copper. Dental amalgams have been used successfully for the restoration of teeth for over 150 years. Found to be safe and beneficial as a restorative material, concerns of mercury toxicity have driven dentists away from the clinical use of amalgam. Composites are made up of resin matrix and bond filler particles. Resin-based composite material continues to gain popularity among dentists to aesthetically improve posterior restorations. While the most common aesthetic replacement to dental amalgam is resin composite, posterior composite restorations, however, have higher risk of restoration failure rates and recurrent caries. In this study, our goal is to compare existing literature that includes data about the success and failure rates of resin composite and dental amalgam posterior restorations. To accomplish this, scientific findings on amalgam vs composite posterior restorations were critically evaluated. Databases used include Google scholar, National Center for Biotechnology and Information (NCBI), and ScienceDirect. According to assessed articles, research studies demonstrate clearly that amalgam has a higher survival rate than composite for posterior restorations and there is more secondary caries associated with resin composite than amalgam in posterior restorations. Restoring posterior teeth with resin composite continues to acquire popularity among dentists and the demand for aesthetic restorations is increasing. Our literature review suggests clinical and patient factors, cavity size, preparation design, and tooth position must be taken into consideration for the selection of any restorative material.

Poster SOD-26

EFFECT OF NEEDLE INSERTION ANGLE ON PAIN DURING LABIAL INFILTRATION ANESTHESIA OF THE ANTERIOR MAXILLA: A RANDOMIZED CLINICAL TRIAL

Amirhossein Moaddabi1 | Tahereh Molania2 | Alireza Arezoumandi3 | Sahar Ghaedsharaf4 | Mariangela Cernera5 Roya Nikbakht6 | Parisa Soltani5,7 | Gianrico Spagnuolo5 | Shirin Shahnaseri8

1Department of Oral and Maxillofacial Surgery, School of Dentistry, Dental Research Center, Mazandaran University of Medical Sciences, Sari, Iran | 2Department of Oral Medicine, Dental Research Center, Faculty of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran | 3Students Research Committee, School of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran | 4Private Practice, Tehran, Iran | 5Department of Neurosciences, Reproductive and Odon-

tostomatological Sciences, University of Naples “Federico II”, Naples, Italy | 6Department of Biostatistics and Epidemiology, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran | 7Department of Oral and Maxillofacial Radiology, School of Dentistry, Dental Implants Research Center, Dental Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran | 8Department of Oral and Maxillofacial Surgery, School of Dentistry, Meharry Medical College, Nashville, Tennesse, USA.

This study aimed to assess the effect of needle insertion angle on pain during labial infiltration anesthesia in the anterior maxillary region.

In this parallel design randomized clinical trial, participants were randomly assigned to four groups for labial infiltration anesthesia of the anterior maxilla. Local anesthesia was performed with needle orientation parallel to the longitudinal axis of the tooth using a conventional syringe (Syringe-0), needle at α angle with a conventional syringe (Syringe-α), computer-controlled local anesthetic delivery (CCLAD) device parallel to the longitudinal axis of the tooth (CCLAD-0), and CCLAD at α angle (CCLAD-α). The heart rate (HR), blood pressure (BP), and respiratory rate (RR) of participants were measured before needle insertion, immediately after needle insertion, and immediately after the injection by vital signs monitor. The level of pain experienced by participants was quantified using a numerical rating scale (NRS). Data were analyzed by repeated-measures ANOVA and regression models (α = 0.05).

Thirty-six participants aged from 21 to 60 years, with a mean age of 35.36 years were recruited. The mean pain scores were 7.44, 4.67, 2.89, and 0.67 in groups Syringe-0, Syringe-α, CCLAD-0, and CCLAD-α, respectively (p < 0.001). Age and sex had no significant effect on pain scores (p = 0.914 and p = 0.702, respectively). The four groups had no significant difference in vital signs (p > 0.05). Injection at an α angle and the application of CCLAD can be used in clinical practice to decrease the pain experienced by participants during labial infiltration anesthesia of the anterior maxilla.

This work was financially supported by Mazandaran University of Medical Sciences (#9621). Open access publishing facilitated by Universita degli Studi di Napoli Federico II, as part of the Wiley - CRUI-CARE agreement.

Poster SOD-27

E-CIGARETTE USE IN THE ADOLESCENT AND YOUNG ADULT POPULATIONS

Melissa D. Porter1 , Theodore Williams2, Jada Pierre2, Taylor Swett2, Ethel Harris3

1Department of Pediatric Dentistry, Pediatric Residency Program, School of Dentistry, Meharry Medical College, Nashville, TN.

2School of Dentistry, Meharry Medical College, Nashville, TN.

3Department of Internal Medicine, Meharry Community Wellness Center, School of Medicine, Meharry Medical College, Nashville, TN.

E-cigarettes are battery operated devices that contain nicotine and other harmful chemicals, often used as a cigarette alternative. This project will explore e-cigarette use, the social factors influencing use, the effects on systemic health associated with e-cigarette use, and the role of healthcare providers in addressing this issue, and strategies for cessation among adolescents and young adults. The information was compiled by gathering data, developing a questionnaire survey targeting target populations with an extensive review of existing literature and previous studies. The questionnaire focuses on understanding the social, psychological, and environmental factors that lead to e-cigarette use. The data gathered will be analyzed to identify trends, risk factors, and help develop cessation strategies. Previous data indicate that use among the target population continues to increase at alarming rates. National data show that in 2023, about 1 out of every 22 middle school students (4.6%) and 1 out of every 10 high school students (10%), respectively, reported that they had used e-cigarettes in the past 30 days. Multi-level factors that influence e-cigarette use among the target populations include, demographics, beliefs and perceptions about e-cigarettes (individual); friend, parent/caregiver e-cigarette use and associated beliefs and behaviors (interpersonal); access to e-cigarette retailers and school-related characteristics (community); and media exposure and policies (environmental). E-cigarette use among the target population is driven by a combination of social influences, psychological factors, and misconceptions about the safety of these products. The health risks associated with e-cigarettes intensify the need for targeted interventions to prevent adolescents and young adults from beginning the

habit and support cessation. These findings underscore the importance of the role health care providers, physicians and dentists play in educating these populations and that further study is needed to develop and implement strategies to reduce e-cigarette use.

Dental student research is partly supported by the HRSA-COE funding (D34HP00002) to the School of Dentistry, Meharry Medical College, and Nashville, Tennessee.

School of Graduate Studies

Poster SOGS-1

PREDICTED

PLACENTAL GENE EXPRESSION LINKS ENDOMETRIOSIS, UTERINE FIBROIDS, AND POLYCYSTIC OVARIAN SYNDROME

Alexis T. Pigg Akerele1-4, Jeewoo Kim3,4,5 Elizabeth A. Jasper4, Jacklyn N. Hellwege3,5, Todd L. Edwards6, and Digna R. Velez Edwards4

1School of Graduate Studies; 2Department of Microbiology, Immunology and Physiology, Meharry Medical College; 3Vanderbilt Genetics Institute, Vanderbilt University; 4Division of Quantitative and Clinical Science, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center; 5,5Division of Genetic Medicine, Department of Medicine; 6Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN

Mother-to-child disease transmission begins in utero, with the placenta being crucial to offspring health. Evidence links adult-onset diseases with placental gene expression. Here we explore whether placental gene expression may also influence the development of endometriosis (ENDO), polycystic ovarian syndrome (PCOS), and uterine leiomyoma (fibroids, UFs), three common gynecologic diseases, which feature similar symptoms and have few fertility-preserving treatments. ENDO, PCOS, and UFs often co-occur, and are linked to increased chronic disease risk, yet the underlying mechanisms remain poorly understood. In this study, we evaluated the relationship between ENDO, UFs, and PCOS and placental genetically predicted gene expression (GPGE). Multi-ancestry summary statistics were meta-analyzed from published studies for ENDO (24,818 cases and 501,407 controls), UFs (44,205 cases and 356,552 controls), and PCOS (10,074 cases and 103,164 controls). We evaluated associations using S-PrediXcan across GTEX v7 tissues and a published placental eQTL study. The significant gene list for placenta was filtered against 48 other tissue types to identify placenta-specific gene associations. Fifteen genes associated with UFs and PCOS were significantly predicted to be uniquely expressed in the placenta. Notably, glycoprotein gene CD109, associated with UFs, was reported in the GWAS catalogue and literature to be linked to endometriosis, increased diastolic blood pressure, and reduced calcium levels (a factor associated with UFs, PCOS, and ENDO). Two genes, ATF4P4 and NIN, were only associated with PCOS in GPGE from placenta. ATF4P4 influences sex hormone-binding globulin levels, previously implicated in UFs, PCOS, and severe ENDO, while NIN regulates angiogenic processes, which is essential for UFs and endometriosis tissue growth and survival. These findings suggest a complex genetic network linking the placenta to the development gynecologic diseases. Our results further support a developmental origin of these conditions, with placental gene expression potentially serving as a mechanistic link between in utero exposures and health later in life.

Support for this research was provided, in part, by the National Institutes of Health through the following grants: R01HD093671, R01HD074711, R03HD078567, and 5T32HL007737.

Poster SOGS-2

SEMI-AUTOMATED ROBOTIC SAMPLE PREPARATION FOR SCALABLE BOTTOM-UP CLINICAL PROTEOMIC PIPELINES

Angel C. Bodrick1-2, Leena Patil1, Renã A. S. Robinson1-6

1Department of Chemistry, Vanderbilt University, Nashville, TN, 2Department of Biomedical Sciences, Meharry Medical

College, Nashville, TN, 3Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 4Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, 5Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, 6Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN

Alzheimer’s Disease (AD) is a neurodegenerative disorder that slowly impairs memory and cognitive functions. In the United States, AD is the fifth leading cause of death for adults aged 65 years and older. Proteomics can further the understanding of molecular contributors to AD through large-scale analysis. However, performing large-scale proteomics is challenging as there are several sample preparation stages, and months of LC-MS/MS data acquisition. Complex sample analysis steps can be tedious and large technical variations can be introduced. Therefore, this study aims to transfer manual protocols to a Biomek i7 automated robotic liquid handler workstation towards the goal of analyzing large numbers of AD post-mortem brain tissues.

To establish the method, five computer simulations, two dry trials without samples, and three water trials were conducted. To validate the method, post-mortem pre-frontal cortex tissues were used as a test sample and divided into ten portions. These samples were processed using a semi-automated bottom-up proteomics workflow. The Biomek i7 was utilized to perform six experimental steps: protein quantification assays, digestion, sample cleanup, TMT labeling, pooling, and aliquoting. Overall, the Biomek approach reduces the time five-fold as compared to a manual sample preparation strategy and will result in an estimated 20% reduction in consumable costs.

This presentation will showcase reduced sample preparation time, lower costs, less technical variation, and increased sample capacity by automating manual protocols. The demand for automation is growing, and this study enhances the reproducibility and reliability of results, which is essential for clinical decision-making for AD.

This project was supported, in part, by TN Doctoral Scholars Grant, and the National Institutes of Health (R01AG064950, RASR).

Poster SOGS-3

UNRAVELING THE ROLE OF TMEM135 IN THE STRUCTURAL AND FUNCTIONAL CHANGES OF DIABETIC CARDIOMYOPATHY

1Department of Molecular Physiology & Biophysics, Vanderbilt University

2Department of Biomedical Sciences, Meharry Medical College

The occurrence of heart failure (HF), remains a critical and growing worldwide public health issue, affecting 26 million individuals globally (5.7 million in the U.S.), with annual U.S. costs of up to $60 billion. Despite this tremendous economic and social burden, especially in underrepresented communities, personalized medicines remain limited. Individuals with diabetes can develop a form of heart failure called diabetic cardiomyopathy (DCM). DCM is characterized by the absence of coronary artery disease, hypertension, or other conventional cardiac pathologies, making it particularly challenging to diagnose and treat. Rather, DCM has a unique pathology, arising directly from metabolic syndrome. In DCM, the cardiac muscle becomes thin and weakened, which has direct implications in being caused by changes in Mitochondria (Mito) structure and function. Transmembrane protein 135 (TMEM135) is known for its roles in lipid metabolism and also acts as a mitochondrial fission factor through mitochondrial-peroxisome interactions. More recently, novel single-nucleotide polymorphisms (SNPs) within TMEM135 have been associated with heart failure. Our preliminary data has found that TMEM135 RNA levels, via qPCR, are elevated in obese and lean human HF compared to controls. While it has not been thoroughly studied in the context of HF yet, it is a promising regulator due to its pluralistic roles in the regulation of mitochondrial structure and calcium signaling. The overall goal of our research is to advance the understanding of TMEM135’s role in DCM and its role in ultrastructure.

Ashton Oliver1,2, Benjamin Rodriguez1,2, Han Le1,2, Andrea Marshall1,2, Heather Beasley1,2, Antentor Hinton Jr.1,2

INVESTIGATING THE ROLE OF FXR SIGNALING IN THE HYPEROXIC PHASE OF RETINOPATHY OF PREMATURITY (ROP)

Briah Bailey1, Menaka Thounaojam2

Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College

Retinopathy of prematurity (ROP) is an ocular complication of the retina characterized by abnormal blood vessel development which can result in scarring, retinal detachment, and permanent loss of vision. ROP primarily affects preterm infants and serves as the leading cause of childhood blindness worldwide. Preventing blindness in premature babies with ROP necessitates new therapies for early stages, as existing treatments for later stages come with significant drawbacks. The role of Farnesoid-X-Receptor (FXR), a bile acid receptor, in inflammation and angiogenesis is explored in extraocular pathologies. Supplemental oxygen and neonatal hyperglycemia, especially in low-birth-weight infants, are major risk factors for Phase I ROP. Building on our prior research, we hypothesize that changes in retinal FXR signaling might be a key contributor to retinal abnormalities observed in the hyperglycemia model (HAR) of phase I ROP. Streptozotocin (STZ, 50 mg/ kg) was injected daily into the peritoneal cavity of wild-type (WT HAR) mice and FXR Knockout (FXR-/- HAR mice) from postnatal day 1 to postnatal day 9. At P10, body weight and blood glucose levels were measured, and retinas were collected. Retinal flat mounts were stained with isolectin B4 to determine the vascular distribution. H&E and immunohistochemical staining were performed in cryosections to examine retinal astrocytes and neuronal cells. FXR-/- HAR showed a lower body weight and higher blood glucose when compared to WT HAR. Unbiased vascular network analysis using AngioTool revealed that FXR-/- HAR mice had increased vessel length, junction density, and fewer endpoints compared to WT HAR mice. Further, FXR-/- HAR showed more gliosis and more neuronal death compared to WT HAR mice. Our data suggests that FXR signaling plays a significant role in Phase I ROP pathology and can be targeted as a new therapeutic tool in limiting ROP pathology.

Poster SOGS-5

COGNITIVE DECLINE MECHANISMS IN A MOUSE MODEL OF ARTERIAL STIFFENING

C. Jeff, S Reasonover, A. Santner, M. Sobanko, D. G. Harrison, M. M. Santisteban

Meharry Medical College (CJ); Vanderbilt University (AS, MS); Vanderbilt University Medical Center (DGH, MMS)

Dementia affects approximately 50 million adults worldwide and is a leading contributor to mortality and disability. Cardiovascular risk factors, such as hypertension and arterial stiffening, are recognized as important contributors to dementia. Aortic stiffening is linked to cognitive deficits and biomarkers of neurodegeneration; however, the molecular mechanisms remain largely unexplored. The objective of this study is to address how arterial stiffness affects cognitive function. We hypothesize that arterial stiffening induces neuroinflammation and reduces cerebral blood flow (CBF), which synergistically promotes cognitive impairment.

We induced a brief episode of hypertension in 3-month-old male C57BL/6 mice via a two-week s.c. infusion of angiotensin II (Ang II; 600ng/kg/min) using osmotic mini pumps. Blood pressure was measured twice weekly by tail-cuff plethysmography. We assessed cognitive function at 1-, 2-, and 3-months post-infusion using neurobehavioral assays (n=11-16 mice/group) evaluating spatial working memory (Y-maze), recognition memory (Novel Object Recognition), spatial learning (Barnes maze), and daily activities (Nest Building). We also measured absolute resting cerebral blood flow (CBF) by ASL-MRI and assessed neuroinflammation in the cortex and hippocampus using immunohistochemistry for microglia (Iba1) and astrocytes (GFAP).

Systolic blood pressure increased during Ang II infusion and returned to normal after pump removal on day 14. Ang II exposure led to deficits in spatial, recognition, and long-term memory at 2 months post-infusion. CBF was drastically reduced in both the cortex and hippocampus, and microglia density increased in the cortex of Ang II-treated mice after 3 months.

Our study finds that arterial stiffening induced by a brief episode of hypertension leads to cognitive impairment associated with a reduction in CBF and concomitant gliosis in the brain’s memory centers.

This study is funded by the NIH K22 NS 123507 and Alzheimer’s Association AARGD-24-1293605 grants.

Poster SOGS-6

Ifi27l2a: THE MISSING LINK IN MICROGLIAL REGULATION OF RETINOPATHY OF PREMATURITY

Chanel Harris1, Josephine Rudd Zhong Manas2, Ravirajsinh N. Jadeja2, Pamela M. Martin1,2 and Menaka C. Thounaojam1,2

1Department of Biomedical Sciences, Meharry Medical College, Nashville, Tennessee

2Department of Biochemistry and Molecular Biology, Augusta University, Augusta, Georgia

Retinopathy of prematurity (ROP) is a vasoproliferative disorder affecting premature infants, particularly those born before 24 weeks of gestation. It arises from abnormal retinal vascular development due to oxygen dysregulation after birth. Initial hyperoxia leads to vessel regression, followed by hypoxia-driven abnormal neovascularization, which can result in retinal detachment and vision loss. Microglia, the resident immune cells of the retina, play a key role in regulating retinal neovascularization (RNV) through programmed cell death and immune responses. This study aims to identify novel microglia-mediated targets that regulate neovascularization using the oxygen-induced retinopathy (OIR) mouse model of ROP.

Retinal tissues from postnatal day 17 (P17) OIR and room air (RA, control) mice were analyzed using single-cell RNA sequencing (scRNA-Seq), which revealed a significant upregulation of microglial activation and pro-inflammatory markers. Notably, Ifi27l2a (interferon alpha-inducible protein 27-like 2A), a gene involved in immune and interferon responses, was the most highly upregulated gene in OIR microglia compared to controls. These findings were validated by quantitative PCR (qPCR) of Ifi27l2a expression across various postnatal stages (P12, P14, and P17) in OIR mice. Immunohistochemistry (IHC) confirmed the localization of Ifi27l2a within microglia through co-localization with the microglial marker IBA-1. Further investigation using human HMC3 microglial cells under hypoxic (2% oxygen) and inflammatory conditions (lipopolysaccharide treatment) demonstrated upregulation of IFI27, the human ortholog of Ifi27l2a, under both conditions. These findings suggest that Ifi27l2a plays a crucial role in microglial activation during retinal hypoxia and inflammation in the OIR model. Overall, this study highlights Ifi27l2a as a potential therapeutic target in microglia-mediated retinal inflammation and neovascularization in ROP.

This research is funded by the NIH grant RO1EY034568.

Poster SOGS-7

GLUCOCORTICOID SIGNALING PROMOTES SALT-SENSITIVE HYPERTENSION VIA INDUCTION OF SGK1 EXPRESSION AND METABOLOMIC SHIFT IN ANTIGEN-PRESENTING CELLS

Claude F. Albritton1,2, Mert Demirci3, Kit Neikirk4, Lale A. Ertuglu3, Jeanne A Ishimwe1, Ashley L Mutchler1, Quanhu Sheng5, Cheryl L Laffer1, Celestine N. Wanjalla1, Taseer Ahmed1,6, Alexandria Porcia Haynes1, Mohammad Saleem1 , Heather K. Beasley4, Andrea G. Marshall4, Zer Vue4, Alp T Ikizler3, Thomas R. Kleyman7, Valentina Kon8, Antentor Hinton4, and Annet Kirabo1,4,9,10,11*

1Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37212-8802, USA.

2 Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, Nashville, TN 37208-3501, USA.

3Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States

4Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN 37212-8802, USA.

5Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37212-8802, USA.

6Department of Pharmacology, College of Pharmacy, University of Sargodha, University Road, Sargodha, Punjab, 40100, Pakistan

7Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.

8Division of Nephrology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.

9Vanderbilt Center for Immunobiology

10Vanderbilt Institute for Infection, Immunology and Inflammation

11Vanderbilt Institute for Global Health

Salt sensitivity of blood pressure (SSBP) is a condition characterized by elevation in blood pressure following increased dietary salt intake through the epithelial sodium channel (ENaC). ENaC activation and stabilization have been implicated by SGK1 activation. However, the mechanistic interplay between SGK1 expression and excess dietary Na+ influx in APCs leading to SSBP has not yet been elucidated. Excess cortisol caused by polymorphic mutations in the HSD11B2 gene has been associated with hypertension. Cortisol has been found to induce SGK1 expression by activating glucocorticoid response elements, and its excess is implicated in mitochondrial dysfunction, which can lead to an altered metabolome. I hypothesize that glucocorticoid signaling promotes SSBP via induction of SGK1 expression, which is coupled with metabolomic shift and mitochondrial distress. To test this, an in-depth metabolomic analysis was conducted on individuals characterized for SSBP using a protocol involving inpatient salt-loading and salt-depletion. From this, I demonstrated that glucocorticoid receptor (NS: 5504.36 ± 1369.10; HS: 5915.73 ± 2391.55; q = 0.043) rather than mineralocorticoid receptor (NS: 56.45 ± 16.65; HS: 75.55 ± 38.43; q = 0.85) is transcribed in a parallel manner to Sgk1 (NS: 11962.91 ± 5474.72; HS: 11195.45 ± 5504.51; q < 0.0001) in monocytes exposed to high salt, and there is a direct correlation between their changes in expression (r > 0.8; p < 0.01). We observed substantial alterations in urine cortisol metabolism due to salt loading/depletion, exhibiting a pattern that aligns with hemodynamic shifts corresponding to SSBP (r > 0.7; p < 0.05). Also, the urinary cortisol-to-cortisone ratio correlated with SSBP (r > 0.6; p < 0.7), and high salt exacerbates these metabolomic changes and induces mitochondrial fragmentation (p < 0.05). Collectively, these data suggest that glucocorticoid signaling in conditions of high salt promotes salt-sensitive hypertension and impacts intracellular metabolomics.

Poster SOGS-8

OSTEOSTATIN (PTHRP 107-111) ACTS ON THE TUMOR MICROENVIRONMENT TO DRIVE ER+ BREAST CANCER BONE COLONIZATION

Déja Grant1,2, Julia Ahn2,3, Lawrence A. Vecchi, III2,3 and Rachelle W. Johnson2,3

1Department of Biochemistry, Cancer Biology, Neuroscience, & Pharmacology, Meharry Medical College, 2Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, 3Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN

Parathyroid hormone-related protein (PTHrP-36-139) expressed by breast cancer cells promotes tumor outgrowth in bone. Osteostatin (PTHrP107-111) is a highly conserved molecule in the PTHrP C-terminus that can be generated by cleavage of PTHrP, but its function is unknown. Since osteostatin is the most conserved region of the C-terminus, we investigated its function in breast cancer bone colonization. We stably expressed an empty vector control or truncated PTHrP-36-67 with deletion of the C-terminus in human MCF7 breast cancer cells, which do not express PTHrP. MCF7 cells or MCF7PTHrP-36-67 cells were inoculated into athymic nude mice by intracardiac injection and treated daily with vehicle (PBS) or recombinant osteostatin (80µg/kg, s.c.). Osteostatin increased tumor burden in the bone marrow in MCF7 mice (2.5fold, p<0.0017), but reduced tumor cells in MCF7-PTHrP-36-67 mice (4.7-fold, p<0.0001), suggesting osteostatin stimulates tumor growth in bone, but is inhibited by PTHrP-36-67. To determine if this was a direct or indirect effect, we treated MCF7 cells with osteostatin in vitro, but there was no activation of downstream signaling. We next determined if the elevated in vivo tumor burden was driven by osteostatin effects on bone. Osteostatin did not alter bone volume in vivo, and although the Tnfsf11/Tnfrsf11b ratio, which promotes osteoclastogenesis, was increased by qPCR (3.3-fold, p<0.0061), Ctsk (4.4-fold, p<0.0432) and CTX-1 serum levels, markers of mature osteoclasts and resorption, were reduced or unchanged, suggesting osteostatin does not impact osteoclastogenesis. However, when examining markers of bone-forming osteoblasts, Runx2, Sp7, and Alpl osteoblast differentiation genes were reduced by osteostatin in MCF7 mice (3.3-9.5fold, p<0.0119). In MCF7-PTHrP-36-67 mice, osteostatin increased serum P1NP levels (1.7-fold, p<0.0463), suggesting

PTHrP-36-67 increases bone formation. Our data suggest that osteostatin stimulates tumor progression in bone, potentially by reducing osteoblast lineage differentiation, and these effects are profoundly impacted by expression of distinct PTHrP isoforms in the microenvironment.

Poster SOGS-9

TRYPANOSOMA CRUZI PARASITE EXTRACTS ALTER TRIPLE NEGATIVE BREAST CANCER TRANSCRIPTOME

Destiny Ball1, Kayla J Rayford2, Ayorinde Cooley3 , Pius Nde+ and Amos Sakwe5 1School of Graduate Studies, 2Department of Microbiology, Immunology and Physiology, School of Medicine, Meharry Medical College, 3,4 Department of Biological Sciences, College of Arts and Sciences, Vanderbilt University, Nashville, TN

The protozoan parasite Trypanosoma cruzi (T. cruzi) causes American trypanosomiasis or Chagas disease. While chronic T. cruzi infection is associated with the development of gastrointestinal and esophageal cancers, protein components of T. cruzi parasite extract as well as cell surface antigens do exhibit anti-tumor effects. This novel study focuses on triple-negative breast cancer (TNBC) that lacks estrogen and progesterone receptors as well as the human epidermal growth factor receptor-2. Compared to other invasive breast cancer types, TNBC patients are often resistant to conventional methods of treatment. Thus, there is a need for nonconventional therapeutics to antagonize tumor progression. Although the molecular mechanism is not well delineated, we aim to understand the role of T.cruzi parasite products on TNBC models. We isolated membrane and cytosolic fractions of T.cruzi trypomastigotes and treated MDA-468 and BT-549 triple-negative breast cancer cell lines with whole parasite, cytosolic and membrane fractions. We then performed cell proliferation and Annexin V-FITC apoptosis assays to evaluate T. cruzi-induced cell death. To identify potential molecular mechanisms, we isolated RNA for RNA sequencing to evaluate alterations in the transcriptome. Our preliminary data show that T. cruzi membrane extracts were more potent than cytosolic extracts at inhibiting the viability of TNBC cells. These parasite extracts significantly affected several pathways, including cellular stress and proinflammatory signaling. Our findings suggest that T. cruzi’s antitumor properties mediate cellular stress, metabolic reprogramming and/or secretion of proinflammatory cytokines in triple negative breast cancer.

Poster SOGS-10

STRUCTURAL AND FUNCTIONAL ENGINEERING OF STREPTOCOCCAL ADHESIN PROTEINS FOR SPECIFIC RECOGNITION OF CANCER-ASSOCIATED SIALOGLYCANS

KeAndreya Morrison1,2, Barbara Bensing3,4, Hai Yu5, Xi Chen5, Paul Sullam3,4, and Tina M Iverson2

1School of Graduate Studies, 2Department of Pharmacology, Vanderbilt University, Nashville, TN, 3Division of Infectious Diseases, Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco, CA, USA, 4the Northern California Institute for Research and Education, San Francisco, CA, USA, 5Department of Chemistry, University of California, Davis, CA, USA

Sialoglycans, glycoconjugates terminated with sialic acid, play critical roles in immune modulation and cancer progression. Neu5Acα2-3Gal-containing sialoglycans, such as those found in salivary mucin and platelet surface proteins, are particularly important in cellular recognition and immune signaling. However, hypersialylation, the overexpression of sialic acid on cell surfaces, is a hallmark of several cancers. Of the many kinds of sialoglycans associated with cancers, 6-O-sulfo-sialyl Lewis X (6S-sLeX) and sialyl Lewis X (sLeX) tend to be the most common targets of hypersialylation. Structural complexity and similarity to other sialoglycans make selective targeting of cancer-associated sialoglycans challenging. Here, we leveraged Siglec-Like Binding Regions (SLBRs) from Streptococcal adhesin proteins to develop engineered probes with selective affinity for distinct sialoglycans, particularly those associated with cancer hypersialylation. We selected two SLBRs, SLBRUB10712 from Streptococcus gordonii and SLBRSK678 from Streptococcus sanguinis, based on their binding preferences for Neu5Acα2-3Gal-containing sialoglycans. Rational design approaches were used to introduce targeted mutations of key residues within the previously determined regulators of SLBR selectivity, the CD, EF, and FG loops. Final rounds of engineering resulted in triple point mutant SLBRUB10712V284T/E285R/Q354D that showed increased specificity for synthetic 6S-sLeX while reducing off-target interactions with other Neu5Acα2-3-

linked glycans via ELISAs. Additionally, we determined a 2.1Å resolution structure of SLBRUB10712E285R/Q354D using X-ray crystallography. Structural analysis of SLBRUB10712E285R/Q354D, and its alphafold predicted counterpart SLBRSK678E298R/Q367D, revealed conformational adjustments that enhance selectivity toward specific sialoglycans. Introduction of valine-to-threonine mutations at residue 284 in SLBRUB10712 (and 297 in SLBRSK678) modulated hydrogen bonding interactions, shifting ligand preferences. These findings establish a framework for developing a library of SLBR-derived probes to study hypersialylation in cancer and immune modulation, offering a promising alternative to traditional glycan detection methods. Future work will focus on optimizing probe affinity and evaluating their utility in cellular and tissue-based assays.

This project is supported, in part, by the National Institutes of Health under award numbers T32AI007281, T32GM14492, and T32HL00773.

Poster SOGS-11

PROTEOMICS ANALYSIS OF ENZALUTAMIDE-TREATED CASTRATION-SENSITIVE AND CASTRATION-RESISTANT PROSTATE CANCER CELL LINES

Lincoln Liburd II1, Siddharth Pratap2, LaMonica Stewart3

1School of Graduate Studies, Meharry Medical College

2Department of Microbiology, Immunology and Physiology, Meharry Medical College

3Department of Biochemistry, Cancer Biology, Neuroscience & Pharmacology, Meharry Medical College

Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer, a disease that disproportionately affects African Americans. However, tumors often progress to metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide (ENZ) and other treatments initially work well for mCRPC, but their effectiveness decreases due to the evolution of tumor resistance.

Our study investigates how ENZ alters biological pathways in castration-sensitive (CS) and castration-resistant (CR) cell lines. We aim to compare whole-proteome expression profiles of two metastatic prostate cancer cell lines, LNCaP (CS) and C4-2B (CR), following ENZ exposure.

In total, 2,812 proteins were identified with high ID stringency (Q-value > -10logP) in the C4-2B cell line. Using Label-Free Quantitation, we observed 161 Differentially Expressed Proteins (DEPs) in the ENZ group, 147 DEPs in the DHT group, and 364 DEPs in the combined DHT + ENZ group. DEPs were mapped to biological pathways in KEGG and REACTOME databases for enrichment analysis using the WEBGESTALT web-app. Notable pathways with significant enrichment score values included “mRNA degradation (KEGG Hsa03018)”, “Rho-GTPase-based activation (REACTOME #R-HSA-5625900; #R-HSA-5627117)”, and “Interleukin-12 (IL-12) (REACTOME #R-HSA-9020591)” pathways.

The “mRNA degradation” and “mRNA alternative splicing/processing” pathways were significantly enriched in the ENZ group. This potentially suggests direct effects on protein expression regulation, potentially leading to adaptive protein synthesis that supports resistance due to ENZ exposure. The significant enrichment of “Rho-GTPase,” “Viral Infection,” and “DNA Repair” pathways in the “DHT + ENZ” group suggests complex alterations in cell signaling and immune interactions that may contribute to therapy resistance by reshaping the tumor microenvironment, enhancing cancer cell adaptability, facilitating immune evasion, and activating “DNA Repair” mechanisms, which may help cancer cells overcome therapy-induced damage and sustain their survival despite treatment pressures.

Poster SOGS-12 FETAL HEMOGLOBIN AND RETINOPATHY OF PREMATURITY

Marcus Jackson1, Gayatri Seth1, Menaka Thounaojam1, Dr. Ravirajsinh Jadeja2, Pamela Martin1

1Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College

2Department of Biochemistry and Molecular Biology, Augusta University Medical college of Georgia

Fetal hemoglobin (HbF) plays a crucial role in oxygen transport during fetal development due to its higher oxygen affinity compared to adult hemoglobin. In preterm infants, the transition from HbF to adult hemoglobin is often disrupted by medical interventions such as red blood cell transfusions, which can lower HbF levels, alter oxygen dynamics, and potentially contribute to the development of retinopathy of prematurity (ROP). Emerging clinical evidence suggests that maintaining higher HbF levels may help stabilize retinal oxygenation and reduce the risk of ROP

This study investigates the role of HbF in retinal development and its relevance in a mouse model of ROP, an oxygen-induced retinopathy (OIR) in mice. We exposed neonatal humanized hemoglobin-expressing TOWNES mice to OIR conditions and collected retinal samples at key disease phases-hyperoxia (P12) and hypoxia (P17).

Our findings revealed a significant disruption in HbF expression, along with alterations in hemoglobin alpha and beta chains. Additionally, we analyzed vascular development in TOWNES mice compared to wild-type C57BL/6J mice to gain further insight into vascular pathology in this humanized model.

Our ongoing studies aim to elucidate the role of HbF in modulating retinal oxygenation and neovascularization. These findings could have significant implications for developing targeted strategies to mitigate ROP risk by preserving HbF levels in preterm infants.

SOIL LEVELS OF PER- AND POLYFLUOROALKYL SUBSTANCES (PFAS): EMERGING ENVIRONMENTAL CONTAMINANTS

Markis’ Hamilton1, Octavia Ailsworth2, Ritu Chauhan1, Thanigaivelan Kanagasabai1, Ngee Chong3, Pius Nde4 , Anil Shanker1, Aramandla Ramesh1

1Department of Biochemistry, Cancer Biology, Neuroscience & Pharmacology, School of Medicine, Meharry Medical College, 2Department of Public Health, School of Global Health, Meharry Medical College, 3Department of Chemistry, Middle Tennessee State University, and 4Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College

Per- and polyfluoroalkyl substances (PFAS), also known as “forever chemicals,” have been widely used in industrial and consumer products. Their strong carbon-fluorine bonds make them highly resistant to degradation, contributing to environmental contamination and serious health risks, such as cancer risk, reproductive and developmental complications. In this study, PFAS levels in ground and roadside soil samples were analyzed using liquid chromatography-mass spectrometry (LC/MS). Samples were collected, processed, and extracted using a solid-phase extraction (SPE) method to isolate PFAS compounds, followed by carbon cleanup to remove particulates prior to injection on to LC/MS.

PFAS concentrations were compared to EPA acceptable limits for PFOS (Perfluorooctane sulfonic acid) (130 ng/g), PFOA (Perfluorooctanoic acid) (190 ng/g), and PFNA (Perfluorononanoic acid) (190 ng/g), revealing significant elevations. PFOS levels were highest in garden soil sample 1 (402 ng/g) and roadside soil sample 3 (617 ng/g), while PFOA peaked in garden soil sample 1 (548 ng/g) and roadside soil sample 3 (534 ng/g). PFNA concentrations were notably elevated in garden soil sample 1 (1414 ng/g) and sample 2 (597 ng/g) but lower in roadside soil sample 3 (115 ng/g) and sample 4 (1.8 ng/g), suggesting that soil composition may influence PFAS retention.

Overall, our preliminary studies highlight the significant environmental pollution caused by PFAS and the likelihood of health risks associated with exposure. To mitigate contamination, exploring safer alternatives to PFAS chemicals is crucial. Additional approaches that could be used to remove PFAS contamination are microbial- and thermal degradation.

We would like to acknowledge funding from the DOE grants DE-EM0005266, and DOE-BSRA G-SOW-A-02557.

Poster SOGS-13

MECHANISTIC

INSIGHTS INTO PHARMACOLOGICAL INTERVENTIONS FOR RESCUING GAT-1 FUNCTION IN SLC6A1 VARIANTS

Melissa Deleeuw1,3,4, Wangzhen Shen4, Jing-Qiong Kang2,3,4

1Department of Biomedical Sciences, Meharry Medical College, Nashville, TN, 2 Department of Pharmacology, Vanderbilt University, 3Vanderbilt University Brain Institute 4 Department. of Neurology, Vanderbilt University Medical Center

SLC6A1 encodes GABA transporter 1 (GAT-1), a key regulator of inhibitory neurotransmission in the central nervous system. Pathogenic SLC6A1 variants are the genetic foundation of developmental epileptic encephalopathies (DEEs), often resistant to current therapies. This study aimed to elucidate the mechanisms by which pharmacological chaperones and histone deacetylase (HDAC) inhibitors restore GAT-1 function across 32 distinct SLC6A1 variants. Here, we evaluated two classes of compounds: pharmacochaperones (4-phenylbutyrate [PBA] and tauroursodeoxycholic acid [TUDCA]) and HDAC inhibitors (butyrate and suberoylanilide hydroxamic acid [SAHA]). All agents were tested in HEK293T cells expressing mutant GAT-1 transporters. We conducted [3H]-GABA uptake assays, microsome isolation, end-point fluorescence assays, EEG recordings on knockin mice, and Western blot analyses, to quantify functional rescue and protein expression.

Results indicate that chaperone drugs such as PBA and TUDCA significantly improved GABA uptake and GAT-1 surface expression, outperforming HDAC inhibitors. PBA’s ability to reduce endoplasmic reticulum (ER) stress and enhance protein folding and trafficking likely underlies these effects, aligning with prior research identifying ER stress as a key pathomechanism of SLC6A1 mutations. In contrast, butyrate provided modest short-term improvements in GAT-1 function but caused a marked decline in GABA uptake and protein expression over time, suggesting potential long-term collateral dysfunction of GAT-1 with prolonged HDAC inhibitor use.

These findings highlight the superior rescue efficacy of pharmacochaperones compared to HDAC inhibitors, emphasizing PBA’s dual role as a pharmacochaperone and HDAC inhibitor. Further investigation is needed to delineate the extent to which PBA’s therapeutic benefits derive from its chaperone properties versus HDAC inhibition, guiding strategies for optimizing treatments for SLC6A1-related disorders.

We acknowledge funding from the National Institutes of Health under award numbers T32AI007281, T32GM14492, and T32HL00773, and NS82635, SLC6A1 Connect, Taysha Gene Therapies, and NIH R01 NS121718.

Poster SOGS-15

TUSC2 MODULATES THE ANTI-TUMOR FUNCTION OF THE CYTOTOXIC CELLS

Muna Mohammed1, Salvador Gonzalez Ochoa1, Jane Tonello1, Mark Berger2, Alla Ivanova3, and Anil Shanker1,3

1Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, Nashville, TN 37208, 2Genprex, Inc, 3Department of Biochemistry, Cancer Biology, Neuroscience & Pharmacology, School of Medicine, Meharry Medical College

The Tumor Suppressor Candidate 2 (TUSC2), located on chromosomal region 3p21.3, is frequently deleted in various cancers, including non-small cell lung carcinoma (NSCLC), mesothelioma, breast, and head-and-neck cancers. TUSC2 suppresses cell proliferation and induces apoptosis in cancer cells. Notably, its protein expression is reduced or absent in 80% of NSCLC and all small cell lung carcinoma (SCLC) cases. Loss of TUSC2 in NSCLC is associated with significantly worse overall survival. Our earlier studies identified TUSC2 as a mitochondrial protein involved in cellular calcium regulation and immune cell modulation. While its pro-apoptotic role in cancer cells is established, the impact of TUSC2 deficiency on immune cells remains unclear. We hypothesized that TUSC2 deficiency in immune cells alters their phenotype and anti-tumor response.

Immune cells were isolated from lymphoid organs of Tusc2 knockout (Tusc2 KO) and wild-type (Tusc2 WT) mice for flow cytometry analysis to assess the effect of TUSC2 deficiency on lymphoid cell phenotypes. Mice were then challenged

with syngeneic tumor cell lines to evaluate tumor response in the presence and absence of TUSC2 restoration through intravenous injection of Quaratusugene ozeplasmid (quar oze lipoparticles to TUSC2 KO mice. After three weeks, tumor-infiltrating leukocytes (TILs) and effector lymphoid cells were harvested and analyzed to assess the effect of TUSC2 on anti-tumor NK and T cell responses.

NK cells were skewed to the immature phenotype in Tusc2 KO mice, though their cytotoxic molecules remained unchanged. While naïve T cells were minimally affected by TUSC2 deficiency, their activation and cytotoxic molecules were impaired. In tumor-challenged mice, the cytotoxic functions of both NK and T cells were markedly compromised. Restoration of TUSC2 improved anti-tumor response and increased the infiltration of cytotoxic cells into tumors. TUSC2 has little effect on naïve NK and T cell phenotypes; however, it is crucial for their activation and anti-tumor effector function.

This project was supported by: Microbial Pathogenesis Training Program(T32), Meharry Medical College Core Facilities, which are supported by NIH Grants MD007586, CA163069, and S10RR025497”, Meharry Medical College Animal Care Facility, Grant “Glycolytic Metabolism in TUSC2 Deficiency” provided by Geneprex, Inc.

Poster SOGS-16

DISTINGUISHING ANXA6-DEPENDENT INVASIVENESS OF BASAL-LIKE VERSUS MESENCHYMAL-LIKE TRIPLE-NEGATIVE BREAST CANCER

Perrin Black, Jeremy Wallace, Amos M. Sakwe

Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks estrogen, progesterone, and HER2 receptors. It is characterized by robust tumor growth and metastasis, resistance to therapies, tumoral heterogeneity, and overall worse prognosis, severely limiting treatment options for patients compared to other breast cancer subtypes. Annexin A6 (AnxA6) is a multifunctional calcium-dependent scaffolding protein that in TNBC, is implicated in cell proliferation, motility, and drug resistance. Our preliminary data show differences in the expression of AnxA6 as well as markers of invasiveness among highly invasive mesenchymal-like (MSL) and rapidly growing basal-like (BSL) TNBC cells, suggesting that the invasiveness of these two TNBC subsets may be differentially influenced. While previous studies have demonstrated molecular differences among different TNBC subsets, there has yet to be any work that highlights the role that AnxA6 may play in influencing key aspects of invasiveness between MSL and BSL TNBC phenotypes. Therefore, a more refined understanding of the different mechanisms that drive the invasive and metastatic potential of these TNBC subsets may lead to identification of molecular targets to eventually be exploited by therapeutics to further attenuate metastasis for TNBC patients – the leading cause of TNBC patient mortality. To better understand these differences, a series of invasion assays via Boyden chambers were performed in model MSL and BSL TNBC cell lines to isolate and characterize the invasive subpopulations of the two TNBC phenotypes. These invasive subpopulations will be compared to their noninvasive parental counterparts, in addition to the utilization of short hairpin RNA targeting AnxA6 for assessment of AnxA6-dependence. The invasive subpopulations will be assessed for differences in invasive potential, resistance to chemotherapeutics, cancer stem cell expression, and differential gene expression. We currently hypothesize that invasiveness in MSL TNBC cells will be mediated by distinct molecular targets compared to that in BSL TNBC cells.

Poster SOGS-17

VERIFICATION OF HUMANIZED MOUSE MODELS IN STUDYING DIABETIC RETINOPATHY OUTCOMES

Railyn Webster, Pamela Martin Department of Biomedical Sciences, Meharry Medical College

Diabetes (DBs) is a major health concern in the United States. There are over 20 million adult cases, with ~90% being Type 2. It is also known that people from minority populations, specifically Black Americans, are more likely to develop diabetes even when controlling for socioeconomic factors. In addition to DBs increased prevalence among Black Amer-

icans, they are also more susceptible to complications like diabetic retinopathy (DR), and more severe outcomes. DR is the leading cause of irreversible vision loss and blindness worldwide, making it a major concern for further discovery Currently, DR treatment includes maintaining glycemic control, which has been shown to be difficult and not completely effective in addressing DR risk, laser photo conjugation and repeated intravitreal injection of anti-VEGF therapies which are reserved for the proliferative form of DR, as it is a progressive disease. To date there have been no clinical treatment methods designed to slow or stop the progression of DR. The genetic aspect of DBs and DR prevalence and progression has also yet to be fully explored. This project addresses the lack of adequate treatment and prevention strategies of DR, by establishing a new animal model designed to better replicate the human genome, especially as it concerns hemoglobin (Hb) gene variants and Black Americans. Implementing a more representative model to study these diseases serves to improve the quality of care/treatment that DR patients can receive, leading to better clinical management options, and less severe outcomes.

Poster SOGS-18

TRYPANOSOMA CRUZI EXTRACTS

INDUCE EXPRESSION OF PRO-INFLAMMATORY PROTEINS IN TRIPLE-NEGATIVE BREAST CANCER CELLS

Said B. Gonzalez, Pushkar Shivam, Inmar Osi, Destiny Ball, Ayorinde Cooley, Kayla Rayford, Amos M. Sakwe and Pius N. Nde

Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College

Breast cancer (BC) is the second most common cancer and leading cause of cancer death among women worldwide, with triple-negative breast cancer (TNBC) being an aggressive subtype linked to poor outcomes and comorbidities, like cancer-induced hypercalcemia (CIH) and metastasis. The high mortality rate highlights the need for better research, early detection, and safer, less invasive treatments. While current therapies like chemotherapy, surgery, and radiation are often insufficient, recent studies are exploring parasite-derived treatments for breast cancer. However, the molecular mechanisms behind the anti-tumor effects of parasites like Trypanosoma cruzi remain unclear. Preliminary data from our lab show that T. cruzi extracts induce significant changes in gene expression and cell death in TNBC cell lines, BT-549 and MDA-MB-468.

In this study, we sought to validate parasite induced differential expressed (DE) genes involved in the regulation of host inflammatory responses, such as Nuclear Factor Kappa B Subunit 1 (NF-κB1), and Interleukin-6 (IL-6), using a proteomic approach. The lysates of BT-549 and MDA-MB-468 cells treated with T. cruzi cytoplasmic and membrane fractions were used in our immunoblot and enzyme linked immunosorbent assay (ELISA) assays. Our immunoblot assays revealed that parasite membrane fractions induced significant upregulation of the potent pro-inflammatory transcription factor NF-κB1 in BT-549 cells, but not in MDA-MB-468 cells. The ELISA assays demonstrated that the T. cruzi cytoplasmic fractions induced significant upregulation of the pro-inflammatory cytokine IL-6 in both BT-549 and MDA-MB-468 cells. Kaplan Meier Survival Plots generated to assess the correlation between pro-inflammatory gene expression and survival in 712 BC patients showed that patients with high expression of NF-κB1 have significantly higher probability of survival than their low expression counterpart. These findings provide new insights into the molecular mechanisms by which T. cruzi extracts modulate pro-inflammatory responses in aggressive BC cells and highlight their potential for the development of novel therapeutics.

This research was supported by funding from a G-RISE grant

School of Medicine

Poster SOM-1

TUMOR DORMANCY WITHIN THE LYMPHOVASCULAR EMBOLUS IS REGULATED BY MULTIPLE METABOLISM-SIGNALING PATHWAYS

Arshiya Dhiman, Yin Ye, Justin Wang, Jordan Dillard, Sanford H. Barsky

Department of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, Scripps Mercy Hospital, MER 35, San Diego, CA 92103

Recently, we demonstrated that cancer dormancy is initiated within the lymphovascular tumor embolus and consists of decreased proliferation and lower mammalian target of rapamycin (mTOR) activity. In the present study, we investigated other intersecting metabolism-signaling pathways that may ultimately determine whether the lymphovascular tumor embolus remains dormant or undergoes cell death. The present study exploited a singular patient-derived xenograft (PDX) of inflammatory breast cancer (Mary-X) that spontaneously forms high density spheroids, the in vitro equivalent of emboli. The AMPK metabolic checkpoint pathway, the mTOR nutrient-responsive cell growth pathway, the P13K/Akt intracellular quiescence regulating pathway, and the calpain-mediated E-cadherin proteolytic pathway responsible for spontaneous spheroidgenesis were also investigated, to determine their relative contributions to dormancy. The levels of phosphorylated AMPK proteins (AMPKα and β subunits) decreased gradually with the formation of MARY-X spheroids in vitro. Rapamycin down-regulated mTOR activity, yet dormancy persisted. LY294002, a PI3K/Akt inhibitor, completely abolished mTOR and induced spheroid disadherence and apoptosis. Compound C (AMPK inhibitor) up-regulated mTOR and induced spheroid disadherence and apoptosis. Increasing cellular metabolism led to cell death, even in enriched medium, whereas growing the spheroids in serum-free media (starvation) did not result in further mTOR inhibition, and dormancy was maintained. An increase in our understanding of dormancy from the standpoint of internal signaling pathways might ultimately provide clues to the external stimuli (starvation, hypoxia or other not yet understood phenomena) that act through these pathways to maintain or disrupt dormancy.

Poster SOM-2

DNA-DAMAGE DIRECTED HIGH-THROUGHPUT SCREEN FOR NOVEL DRUGGABLE TARGETS OF PARPi-RESISTANCE OVARIAN CANCER

Candy Okwena1

,

Bisiayo

E.

1School of Medicine Meharry Medical College

Fashemi2, Moreniola Akande2, and Dineo Khabele MD2

2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine

High-grade serous ovarian cancer is a rare but frequently fatal disease. Platinum-based therapy along with poly ADP ribose polymerase inhibitors (PARPi) maintenance therapy, is recommended to 80% of patients. However, acquired PARPi resistance is an ongoing clinical problem and there is a growing need for the development of more targeted therapies. The Khabele lab has previously shown that epigenetic inhibitors such as entinostat, can re-sensitize ovarian cancer cells to PARPi. The overarching objective is to identify novel epigenetic gene targets that when treated in combination with PARP inhibitors, will lead to synthetic lethality in PARPi-resistant ovarian cancer. The specific objective of this summer project is to identify a reliable method, flow cytometry or immunofluorescence (IF), for assessing DNA damage induced by DNA damaging agent (olaparib) in PARPi resistant ovarian cancer cells. We hypothesize that flow cytometry will be a more optimal screening method than IF for assessing the moderate to high levels of DNA damage in ovarian cancer cells. To do this, we induced DNA damage using increasing concentrations of olaparib and stained for γH2AX, a marker of DNA damage. We next, assessed the levels of DNA damage by comparing flow cytometry and IF. As expected, as the olaparib concentration increases so did the level of γH2AX expression. We found that flow cytometry was the more sensitive method of detecting DNA damage at lower concentrations of olaparib. Next, we used siRNA to partially deplete DNA repair genes RAD51 and PARP1 and used flow cytometry and IF to assess γH2AX production. We found that the partial depletion of these genes resulted in olaparib sensitivity and an increase γH2AX expression at low doses of olaparib. The results from this study will provide aid in the discovery of novel drug targets in the treatment of PARPi resistant ovarian cancer patients.

TRUE CANCER STEM CELLS EXHIBIT RELATIVE DEGREES OF DORMANCY AND GENOMIC STABILITY

Casey Cubitt, Krista Mcphail, Justin Wang, Jordan Dillard, Crystal J. Beard, Yin Ye, Sanford H. Barsky

Department of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, Star Diagnostics Laboratories, 215 E Warm Springs Rd, Ste 108, Las Vegas, NV 89119, Scripps Mercy Hospital, MER 35, San Diego, CA 92103

Cancer stem cells in human tumors have been defined by stem cell markers, embryonal signaling pathways and characteristic biology, ie., namely the ability to repopulate the proliferating population. However, even if these properties can be demonstrated within a tumor cell subpopulation, it does not mean that they are truly hierarchical stem cells because they could have been derived from the proliferating population in a reversible manner. Using a human PDX, Mary-X, that overall expressed a strong cancer stem cell phenotype, the study conducted both GPP-labelled retroviral transfection and fluorescent microsphere uptake studies to distinguish proliferating from dormant cells and array CGH to identify regions of amplifications (gains) and deletions (losses) on the overall Mary-X population and then applied derived probes by FISH on individual cells to identify a genomically stable subpopulation. Whereas 97-99% of the cells expressed retroviral GFP and not fluorescent particles and showed numerous gene amplifications and deletions, approximately 1-3% of the cells showed the opposite. The subpopulation with the retained fluorescent microspheres and exhibiting genomic stability was significantly smaller in size than their GFP-expressing and genomically unstable counterparts. Sorting Mary-X spheroids on the basis of either CD133 or ALDH positivity further enriched for this subpopulation. These studies indicate that a truly biological cancer stem cell subpopulation exists that exhibits both dormancy and genomic stability. This subpopulation could not have been derived from the proliferating and resulting genomically unstable population and therefore represents a truly hierarchical stem cell subpopulation capable of only unidirectional differentiation.

Poster SOM-4

IMPACT OF UNPLANNED 30-DAY READMISSION ON MORTALITY RISK IN PATIENTS WITH SACROCOCCYGEAL CHORDOMAS: A NATIONAL CANCER DATABASE ANALYSIS

David A. Stewart Jr1, Avi N. Albert1, Micheal A. Cobo1, Karim Masrouha2

1 Meharry Medical College, Nashville, Tennessee, 2 Department of Orthopedic Surgery, NYU Langone, New York, New York, USA

Chordomas are rare, slow-growing malignant tumors arising from notochordal remnants, primarily along the axial skeleton, including the spine and skull base. Sacrococcygeal chordomas, located in the sacrum and coccyx, present a significant surgical challenge due to the complex anatomy and proximity to critical structures. Understanding the short- and longterm risks of resection is essential for proper patient counseling. Limited research exists on readmission and mortality risk in this population. This study utilized the National Cancer Database (NCDB) to identify predictors of 30-day readmission following sacrococcygeal chordoma resection.

Data were retrospectively extracted from the NCDB (2004–2021) for patients undergoing sacrococcygeal chordoma resection. Variables included demographics, medical history, tumor characteristics, treatment regimens, and mortality. Patients were categorized based on unplanned 30-day readmission status, and statistical analyses identified significant predictors of readmission.

A total of 962 patients were included, with 56 (5.82%) experiencing a 30-day readmission. A Charlson Comorbidity Score of - 2 was a significant predictor of readmission (OR = 2.64; p = 0.031). No differences in 30-day or 90-day mortality were observed between readmitted and non-readmitted patients. However, the last follow-up mortality rate was significantly higher in the readmitted group (41.5% vs. 26.7%; p = 0.020). The time to last follow-up was similar between groups (75.38 ± 45.06 vs. 75.08 ± 48.3 months; p = 0.964), indicating the mortality difference was not due to differences in follow-up duration.

Unplanned 30-day readmission was associated with higher long-term mortality and increased comorbidities. These findings emphasize the impact of early postoperative complications on long-term survival in sacrococcygeal chordoma patients, potentially reflecting the influence of comorbid conditions in the readmitted cohort.

Oral SOM-5

GLIOBLASTOMA MULTIFORME TUMOR VOLUME AND PERSISTENCE OF CHIMERIC ANTIGEN RECEPTOR T CELLS FOLLOWING NEUROSURGICAL DEBULKING

Devi Veerappan¹,², Reena Thomas², Gordon Li², Michael Iv², Crystal Mackall², Kelly Tanner², Juancarlos Cancilla², Keshni Kumar², Bita Sahaf²

¹Meharry Medical College School of Medicine, ²Stanford University School of Medicine

Glioblastoma Multiforme (GBM) is one of the most common and aggressive high-grade primary brain tumors that arises from the glial cells of the central nervous system and occurs most often in the frontal and temporal lobes. Despite current treatment options, long-term prognosis of GBM remains low with no significant improvement rates. Chimeric antigen receptor (CAR) expressing T cells target the B cell marker CD19 and have shown increased efficacy in B cell lymphomas, and lymphoblastic leukemias suggesting benefits in GBM. This study aims to quantify the persistence of CAR-T cells in the context of GBM tumor volume following neurosurgical debulking procedure. A radiology software known as the Mint Lesion was utilized to provide Tumor Response Assessment by Criteria (TRAC) reports that consist of volumetric measurements of the tumor lesions (target enhancing lesions, non-target enhancing lesions, and non-target non-enhancing lesions). Fluorescence-activated cell sorting (FACS) analysis takes a sample mixture of cells and sorts them into different populations based on specific biomarkers and characteristics. B7-H3 CAR-T cell persistence was increased in patients with a larger post-surgical tumor volume (3.04% Subject 001 with 2438 mm² volume and 2.38% Subject 003 with 224 mm² tumor volume). However, the number of CAR-T cells per 1 mm² was significantly reduced in patients with a larger post-surgical tumor volume (0.0012 cells/mm² Subject 001 and 0.010 cells/mm² Subject 003). This study shows that although there is an overall increased CAR-T cell persistence for a larger tumor volume, the number of CAR-T cells per 1 mm² is significantly smaller for larger tumor volumes, while illustrating that a larger postsurgical tumor bulk volume is correlated with an increased CAR-T cell persistence within 1-week post-infusion. These findings provide novel information and complement other correlative studies as part of the Phase 1 interventional clinical trial for glioblastoma patients.

This project was supported and funded by the Stanford Medicine REACH-HBMC Summer Research Program.

Poster SOM-6

BONE MARROW ORIGIN OF MAMMARY PHAGOCYTIC INTRADUCTAL MACROPHAGES

(FOAM CELLS)

Harleen K. Multani, Krista Mcphail, Justin Wang, Robert M. Hoffman,Yin Ye, Sanford H. Barsky

Department of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, Star Diagnostics Laboratories, 215 E Warm Springs Rd, Ste 108, Las Vegas, NV 89119, Scripps Mercy Hospital, MER 35, San Diego, CA 92103, AntiCancer, Inc. 7917 Ostow St., Suite B, San Diego 92111

Mammary intraductal macrophages (foam cells) in humans are the most encountered cells in nipple aspirate fluid yet their origin remains unproven. These cells increase in pregnancy, proliferative fibrocystic disease and intraductal neoplasia (DCIS) where there is intraductal ectasia and obstruction. Previous immunocytochemical studies have indicated that intraductal foam cells are of macrophage lineage. These foam cells engage in phagocytosis of both endogenous as well as exogenous substances present within the ducts and are not proliferative. Although it has been suggested that foam cells could derive from tissue-specific precursors or circulating monocytes, to date no study has provided direct proof of their origin. In this study we provide evidence in both human and murine bone marrow transplant studies that intraductal foam cells are bone marrow derived. We first studied a registry of sex-mismatched bone marrow transplant recipients who later in life had undergone breast biopsies for either proliferative fibrocystic disease, DCIS or gynecomastia and stud-

ied these biopsies by XY chromosome FISH and informative microsatellite polymorphic markers. The intraductal foam cells were of bone marrow donor origin. Then in the experimental bone marrow transplant murine studies, donor marrow from female ROSA26 containing the lacZ reporter were transplanted into either irradiated female recipient transgenic mice carrying the highly penetrant MMTV-pymT or FVB/N background mice where iPS cells derived from tail vein fibroblasts of FVB/N-Tg(MMTV-PyVT)634Mul/J mice were subsequently injected into their mammary fat pads. In all of the transplanted recipient mice, the intraductal foam cells expressed the β-galactosidase (lacZ) reporter and also co-expressed markers of myeloid-macrophage lineage. The number of donor-derived intraductal foam cells were increased in pseudopregnancy 5-fold and in intraductal neoplasia 10-fold. Although macrophages of different origins and lineages are undoubtedly present within both the murine and human breasts, those macrophages that qualify as phagocytic intraductal foam cells are bone marrow derived.

Poster SOM-7

THE STRUCTURE AND FUNCTION OF TBTIM50, A PAP ENZYME, AND AN IMPORTANT VIRULENCE FACTOR FOR TRYPANOSOMA BRUCEI INFECTION

Hira Karim1, Pankaj Sharma2, Jamaine Davis3, Tina M Iverson2, Minu Chaudhuri1

1Department of Microbiology, Immunology, and Physiology, School of Medicine, Meharry Medical College, Nashville TN 37208

2Department of Pharmacology and Biochemistry, School of Medicine, Vanderbilt University, Nashville TN 37208

3Department of Biochemistry, Cancer Biology, Neuroscience, and Pharmacology, School of Medicine, Meharry Medical College, Nashville TN 37208

Trypanosoma brucei is a parasitic protozoan and the causative agent for African trypanosomiasis, a fatal disease in humans and ruminants. T. brucei possesses a single reticular mitochondrion. The translocase of the mitochondrial inner membrane in T. brucei (TbTIM) imports most of the mitochondrial proteins from the cytosol and is structurally and functionally distinct from its counterparts in fungi and humans. TbTIM consists of a few conserved Tim subunits and several other trypanosome-specific proteins. We identified a Tim50 homologue in T. brucei (TbTim50). Unlike Tim50s in other eukaryotes, TbTim50 lacks a transmembrane domain within the N-terminal half but possesses a conserved C-terminal domain phosphatase motif with a perfect signature sequence, DXDX(T/V). Previously, we showed that the recombinant TbTim50 has phosphatidic acid phosphatase (PAP) activity, mutation of the Ds in the active site abolished this activity, and it binds specifically with PA. A global lipidomic analysis revealed a significant down regulation in the levels of triacyl- and diacylglycerol (TAG and DAG), as well as the levels of the phosphatidylcholine (PE) and phosphatidylethanolamine (PE) in TbTim50 knockdown vs control parasite, indicating that TbTim50 is indeed a PAP and plays role in membrane lipid biogenesis. Structural modeling of TbTim50 revealed that the C-terminal domain (200-423 residues), is organized around a Rossmann-like fold, but the N-terminal domain (1-199 residues), is an intrinsically disordered region (IDR). We hypothesize that this IDR is responsible for TbTim50 membrane association and regulation of its activity. We have purified the recombinant full length TbTim50, and the individual N- and C-terminal domains. Applying the structure-function approach, we will determine the experimental structure of this protein and investigate the role of intrinsic disorder domain in the mechanism of action of TbTim50, which is an important virulence factor for T. brucei infection.

Supported by MCB-2401909, NSF (MC), R01AI125662 and NIAID/NIH (MC)

Poster SOM-8

GEOMETRIC TUMOR EMBOLIC BUDDING CHARACTERIZES INFLAMMATORY BREAST CANCER

My-Lan N. Le, Arnav P. Modi, Julie P.T. Nguyen, Justin Wang, Jonathan S. Ahn, William A. Libling, Jacob M. Klein, Preeanka Mazumder, Sanford H. Barsky

Department of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, California University of Science and Medicine, 1501 Violet Street, Colton, CA 92324

The sina qua non of IBC is numerous tumor emboli especially within dermal lymphatics. The explanation remains a mystery. In observational human studies, there was a dramatic exponential or geometric difference in embolic density and a significant difference in embolic size distribution in IBC v non-IBC. In companion experimental studies using contrasting properties of two xenografts, Mary-X and Karen-X, both derived from IBC patients, this study offers a novel explanation and mechanism to explain the high IBC embolic numbers. The explanation is geometric budding. Mary-X exhibits florid lymphovascular tumor emboli in vivo which give rise to high numbers of CTCs and pulmonary metastases whereas Karen-X lacks these features. Mary-X also gives rise to tight spheroids in vitro which exhibit dynamic budding whereas Karen-X exhibits only loose non-budding aggregates. Furthermore Mary-X emboli also bud dramatically into daughter emboli in vivo. The mechanism that regulates this involves the generation of E-cad/NTF1, a calpain-mediated cleavage product of membrane E-cadherin. Inhibiting the generation of E-cad/NFT1 by blocking either the calpain site of cleavage (SC) or the site of binding (SB) with specific decapeptides both reduces spheroid compactness and decreases budding. Since E-cad/NFT1 retains the p120ctn binding site but loses the α-and β-catenin sites, promoting its 360° distribution around the cell’s membrane, the vacilating levels of this molecule trigger budding of both the spheroids as well as the emboli. Recurrent and geometric budding of parental emboli into daughter emboli then would account for the plethora of emboli seen in IBC.

Poster SOM-9

INITIATION OF TUMOR DORMANCY BY THE LYMPHOVASCULAR EMBOLUS

My-Lan N. Le, Arshiya Dhiman, Yin Ye, Justin Wang, Michael G. Izban, Billy R. Ballard, Sanford H. Barsky

Department of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, Scripps Mercy Hospital, MER 35, San Diego, CA 92103

Cancer dormancy followed by recurrence remains an enigma in cancer biology. Since both local and systemic recurrences are thought to emanate from dormant micrometastasis which take origin from lymphovascular tumor emboli we wondered whether the process of dormancy might initiate within lymphovascular emboli. This study combines experimental studies with a patient derived xenograft (PDX) of inflammatory breast cancer (Mary-X) that spontaneously forms spheroids in vitro and budding lymphovascular tumor emboli in vivo with observational studies utilizing tissue microarrays (TMAs) of human breast cancers. In the experimental studies, Mary-X during both lymphovascular emboli formation in vivo and spheroidgenesis in vitro exhibited decreased proliferation, a G0/G1 cell cycle arrest and decreased mTOR signaling. This induction of dormancy required calpain-mediated E-cadherin proteolysis and was mediated by decreased P13K signaling, resulting in decreased mTOR activity. In observational human breast cancer studies, increased E-cadherin immunoreactivity due to increased E-cad/NTF-1 but both decreased Ki-67 and mTOR activity was observed selectively and differentially within the lymphovascular tumor emboli. Both our experimental as well as observational studies indicate that in vivo lymphovascular tumor emboli and their in vitro spheroid equivalent initiate dormancy through these pathways.

Poster SOM-10

IMMUNE CHECKPOINT INHIBITOR-INDUCED

PSORIASIS: DIAGNOSIS, MANAGE-MENT, AND A REVIEW OF CASES

Jolanta

J. Pach,1 Nina

Mbonu,2

Shaman Bhulla,1 Jeffrey M. Cohen,3 Jonathan S. Leventhal3

1Yale School of Medicine, New Haven, CT, 2Meharry Medical College, Nashville, TN, and 3Department of Dermatology, Yale School of Medicine, New Haven, CT

Psoriasis is an immune-mediated adverse effect of immune checkpoint inhibitors due to T cell overactivation, and it may present de novo or, more commonly, as an exacerbation of pre-existing disease. Immune checkpoint inhibitors (ICIs) are effective anti-suit agents but are associated with immune-related adverse events. ICI-induced psoriasis commonly presents in patients with a history of psoriasis but may occur de novo, and it has a significant physical and psychosocial impact. ICI-induced and non-ICI-induced psoriasis are likely mediated by similar cytokines, and similar treatments are employed.

Topical treatment often suffices, and, when needed, several systemic treatments appear to be effective without impacting anti-tuning response. Development of psoriasis may indicate a superior response to ICIs. Thus, recognition and management of ICI-induced psoriasis is essential to avoid ICI interruption and maximize therapeutic potential.

Poster SOM-11

HUMAN PREDICTION OF AMYLOID STATUS VIA MRI SCANS FOR ELDERLY ADULTS AT RISK OF ALZHEIMER DISEASE

Olamide Sogeke1, Kuong Mi Kang2, Donghoon Kim3 and Greg Zaharchuk3

1School of Medicine, Meharry Medical College, 2Department of Radiology, Seoul National University Hospital, Seoul, South Korea, 3Department of Radiology, School of Medicine, Stanford University, Stanford, CA

Prediction of brain amyloid-beta (Aβ) protein is an important risk factor for Alzheimer’s disease (AD), but current assessment methods are suboptimal, invasive or requiring the use of radiation. Although Magnetic Resonance Imaging (MRI) is not sensitive to Aβ, recent studies employing artificial intelligence (AI) suggest that MRI can be used to predict amyloid status at a rate greater than chance. Given that humans can often outperform AI on clinical tasks, our objective is to investigate whether neuroradiologists can predict amyloid status from MRI studies in an at-risk AD population. We retrieved high-resolution T1 weighted MRI scans (training/test cases: 20/91 with either mild cognitive impairment (MCI) or AD) with paired Positron Emission Tomography (PET) scans that can serve as the gold standard for Aβ prediction. There were 50 amyloid-positive and 41 amyloid-negative cases in the test set. Neuroradiologists will review each MRI test case and assign a score on a 10-point grading scale. A score of 1 indicates a strong confidence in amyloid negativity, whereas a score of 10 indicates a strong confidence in amyloid positivity. Intermediate scores indicate varying levels of confidence in their predictions. We plan to test our hypothesis using metrics such as the balanced accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve. Additionally, we will explore whether adding MRI volumetric segmentation reports significantly improves prediction performance. By leveraging MRI, a safer, economical, and more accessible neuroimaging modality, we aim to facilitate early detection of Aβ burden and better understand the limits of AI approaches.

This project was supported, in part, by the REACH-HBMC Stanford Medicine Summer Research Program.

Poster SOM-12

DIFFERENTIAL EXPRESSION OF ENDOTHELIAL-l (ET1) AND ITS RECEPTORS, ENDOTHELIN RECEPTOR TYPE A (ETAR) AND ENDOTHELIN RECEPTOR TYPE B (ETBR) BETWEEN SUBJECTS WITH NORMAL, TRIPLE NEGATIVE, AND NON-TRIPLE NEGATIVE BREAST CANCER

Pooja

Patel1, Shyamali Mukherjee2, Michael Izban2, Billy Ballard2, Salil K. Das2

1School of Medicine, Meharry Medical College, Nashville, TN, 2Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN

The neuropeptide hormone endothelin (ET-1) plays a significant role in breast cancer invasiveness. Elevated ET-1 levels are linked to decreased disease-specific survival. Despite this, few studies explore the differential expression of ET-1 and its receptors, ETAR and ETBR, in triple-negative breast cancer (TNBC) compared to non-TNBC and normal phenotypes. This study aimed to determine whether ET-1, ETAR, and ETBR expression levels are elevated in TNBC cells compared to non-TNBC and normal cells. A potential correlation between increased ET-1 axis expression and aggressive TNBC phenotypes could position the ET-1 axis as a biomarker for TNBC prognosis and a therapeutic target. To test this hypothesis, we examined the mRNA expression and protein levels of ET-1, ETAR, and ETBR using formalin-fixed paraffin-embedded breast tissue samples from four TNBC subjects and four non-TNBC subjects. Techniques including Western blot, immunofluorescence, and immunohistochemistry quantified differential expression. Western blot analysis indicated that ET-1 levels were 81.6% higher, ETAR levels were 35% higher, and ETBR levels were 30% higher in TNBC cell lines compared to non-TNBC lines. Immunofluorescence revealed stronger ETBR intensity across all cell lines and higher

expression of ET-1 and ETBR in TNBC lines (HCC-1806 and MDA-231). Greater nuclear localization of ETBR was also observed. Immunohistochemical analysis showed approximately 20% higher ET-1, 40% higher ETAR, and 20% higher ETBR positive cells in TNBC tissue versus normal tissue. These findings validate our hypothesis, demonstrating that ET-1 and its receptors are more highly expressed in TNBC than in non-TNBC and normal tissues. The consistency between cell line and tissue sample results suggests that targeting these biomarkers. could guide future pharmaceutical development for TNBC treatment.

Supported by MVTCP U54CA162069 and Fuji Oil Company, Osaka, Japan, and NIH MeTRC5U5AMD007593.

Poster SOM-13

NEURONAL MITOCHONDRIAL DYSFUNCTION AND MICROGLIAL HIV RESERVOIRS AS MARKERS OF NEUROCOGNITIVE DECLINE IN VIRALLY SUPPRESSED AFRICAN AMERICANS.

Ramesh Gogulothu1,2, Vladimir Berthaud1, Tarik Smith1,2, Derek Wilus3, Franklin Nouvet4, Venkateswara Rao Amara1,2, Waldemar Popik1,2

1School of Medicine, Department of Internal Medicine, 2Center for AIDS Health Disparities Research, 3School of Global Health, 4Meharry RCMI Research Capacity Core, Meharry Medical College, Nashville, TN.

African Americans living with HIV experience accelerated neurocognitive aging, driven in part by neuronal mitochondrial dysfunction and persistent HIV reservoirs in brain microglia. Nicotine addiction further exacerbates these effects by promoting oxidative stress and neuroinflammation. Despite effective antiretroviral therapy (ART), active microglial reservoirs continue to contribute to neuronal damage and cognitive decline. In response, our study investigates blood-derived, minimally invasive biomarkers for monitoring neuronal mitochondrial injury and neurocognitive deterioration in this high-risk population.

We isolated neuron-derived extracellular vesicles (NEVs) and microglia-derived extracellular vesicles (MEVs) from peripheral blood samples of African American participants, stratified by HIV status, smoking, and sex. NEVs were analyzed for mitochondrial DNA (mtDNA) content using quantitative PCR (qPCR), while MEVs were evaluated for HIV RNA transcripts via reverse transcription qPCR. Our results demonstrate that HIV-positive men exhibit a significant increase in mtDNA levels in NEVs, with smoking further intensifying neuronal mitochondrial damage. In contrast, women appeared resilient to these alterations regardless of smoking status, suggesting a sex-based difference in susceptibility to neuronal mitochondrial dysfunction and HIV-associated neurocognitive disorders (HAND). Moreover, the detection of HIV RNA transcripts in MEVs from HIV-positive men confirms their potential as biomarkers for active microglial HIV reservoirs. These findings underscore the role of chronic microglial HIV reservoir activity in exacerbating neuronal mitochondrial dysfunction, particularly in the context of nicotine addiction. The innovative biomarkers identified in this study offer promising avenues for early detection and intervention, advancing precision medicine and neuroHIV research, and ultimately improving health outcomes in virally suppressed African Americans.

This research is partly funded by NIH/NIDA R21DA052832 (W.P.)

Poster SOM-14

TRUE OR FALSE? ASSESSING ALOPECIA AREATA (AA) MISINFORMATION IN SOCIAL MEDIA

Shanika Francis1, ANK Agarwal3, Dawn Siegel3, Roxana Daneshjou,2,3

1 School of Medicine, Meharry Medical College, Nashville, TN. 2Department of Dermatology, Stanford University, Stanford, CA. 3Department of Biomedical Data Science, Stanford University, Stanford, CA.

Alopecia Areata (AA) is a hair loss-inducing autoimmune disease that affects men and women from a range of ethnic backgrounds worldwide. As social media platforms and AI chatbots have become key shapers in patient behavior, alopecia patients may also seek treatment online. We aim to review the accuracy of the information about AA on social media and

investigate whether patients receive misinformation which hinders appropriate AA treatment from healthcare providers. It is hypothesized that social media influencers may provide alopecia treatment recommendations that do not address AA specifically. We also hypothesize that social mediainfluencers may be recommending AA treatments with no medical benefit.

YouTube and TikTok sites were used to obtain videos using search criteria #alopecia #alopeciatreatment. Hashtag relevancy was used as video post criteria and standard treatment recommendation guidelines were used to sort data into Accurate and Medical Data-Backed, Varied and Not Medical Data-Backed, Misinformed and/or False or Other categories. Apify,Google Colab, and Python Madlib systems were utilized to graph results.

Data from 120 YouTube posts were 19.1% Accurate and Medical Data-Backed, 7.5% Varied and Not Medical Data-Backed, 73.3% Other with no videos identified as Misinformed and/or False. Content from 269 TikTok posts was 15.9% Accurate and Medical Data-Backed, 5.6% Varied and Not Medical Data-Backed, 1.1% Misinformed and/or False, and 77.3% Other. The majority of applicable videos addressing AA treatments recommended the standard appropriate treatment strongly backed by medical data.

AA patients are accessing generalized information on alopecia and may not always obtain the most accurate information from social media influencers to specifically improve AA. Healthcare stakeholders should ensure that the social media platforms and AI chatbots which patients consult are used as tools of proactive education to combat misinformation related to the condition’s treatment.

SOM-15

TARGETING TYPE 2 INFLAMMATION IN BULLOUS PEMPHIGOID: EXPLORING THE NOVEL ROLE OF UPSTREAM TSLP AND IL-33 AS THERAPEUTIC TARGETS

Tammy Ehimwenma-Point Du Jour¹, Gabriela Soto-Canetti2 , 3, Jordan Talia²

¹ Meharry Medical College School of Medicine, ²Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY3, Ponce Health Sciences University School of Medicine, Ponce, PR

This study explores the theoretical potential of targeting thymic stromal lymphopoietin (TSLP) and interleukin-33 (IL33) to modulate inflammation in bullous pemphigoid (BP). Conventional therapies such as methotrexate, mycophenolate mofetil, and systemic corticosteroids have limitations in their efficacy and adverse event profile. Recent breakthroughs have demonstrated the importance of type 2 inflammation in bullous pemphigoid. A review of current literature and analysis of cytokine pathways in type 2 inflammatory conditions such as atopic dermatitis and asthma, we evaluated the roles of TSLP and IL-33 in the pathogenesis of BP. The therapeutic targeting of these cytokines in related type 2 diseases underscores their promise in BP. Targeting of TSLP or IL-33 alter the inflammatory milieu to inhibit IL-4, IL-5, IL-13, IgE, CCL17 (TARC), & CCL22 (MDC) production, which have all been implicated in the pathogenesis of BP. These findings highlight the potential for targeting TSLP and IL-33 as innovative therapeutic strategies in BP, offering a novel approach to addressing type 2 inflammation in this disease. Therapeutic targeting of these upstream cytokines result in greater efficacy, lower risk of systemic side effects, and improved patient outcomes in BP versus conventional therapies.

Poster SOM-16

BORTEZOMIB IN COMBINATION WITH HDAC11 INHIBITION SUPPRESSES CANCER STEM CELL SELFRENEWAL AND ENHANCES ANTI-TUMOR FUNCTION IN KRASMUT/P53MUT LUNG CANCER

T. Kanagasabai, S. Gonzalez Ochoa, M. Mohammed, J. Tonello, A. Ivanova and A. Shanker

Department of Biochemistry, Cancer Biology, Neuroscience & Pharmacology, School of Medicine, Meharry Medical College

Lung cancer is the second most diagnosed cancer and the leading cause of cancer-related deaths in the US, often marked

Poster

rates. We explored the combinatorial effects of HDAC11 inhibitor (SIS17) and bortezomib (BZB) anti-tumor cancer stem cell self-renewal function in KRASmut/P53mut lung cancer cells and xenograft mice models.

The in vitro anticancer effects of the BZB and HDAC11i combination were evaluated using cell viability, migration, and invasion assays in 344SQ, H23, and H358 cell lines. Additionally, the impact of the combination treatment on key cellular metabolic parameters, including extracellular acidification rate and mitochondrial oxidative phosphorylation (oxygen consumption rate), was assessed using the Seahorse assay. Lastly, the antitumor effects of BZB (1 mg/kg) and HDAC11i (1 mg/kg) combination were evaluated in xenograft mice models.

Our data demonstrated that the BZB–SIS17 combination was more effective in reducing the viability of lung cancer cells in comparison with the individual treatments. This combination also significantly inhibited cell migration and invasion. Moreover, the cancer stem cell marker nanog was notably reduced, along with a substantial decrease in key metabolic parameters. While BZB or SIS17 alone inhibited tumor growth compared to the control, the combination of BZB and SIS17 showed a much more pronounced tumor growth inhibition in xenograft mice models. These findings demonstrate that SIS17 sensitizes cancer cells to BZB and inhibit cancer stem cell self-renewal function, potentially improving the antitumor effects against KRASmut/P53mut lung cancer cells, with an enhanced efficacy of combination treatments without causing significant side effects.

Poster SOM-17

LYMPHOVASCULAR TUMORAL EMBOLI IN INFLAMMATORY BREAST CANCER RESULT FROM HAPTOTAXIS-MEDIATED ENCIRCLING LYMPHANGIOGENESIS

Vidhi Dave, Justin Wang, Robert M. Hoffman, Yin Ye, Jordan Dillard, Sanford H. Barsky

Department of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, Scripps Mercy Hospital, MER 35, San Diego, CA 92103, AntiCancer, Inc. 7917 Ostow St., Suite B, San Diego 92111

Inflammatory breast cancer (IBC) is characterized by numerous tumor emboli within lymphatics. In a recent study we observed tumor embolic budding both in vitro and in vivo within lymphovascular spaces and proposed this to account for the plethora of tumor emboli seen in IBC. These observations did not address, however, how lymphovascular invasion is initiated nor the mechanisms involved. In present studies using the well characterized patient-derived xenograft (PDX), Mary-X, which exhibited florid lymphovascular invasion (LVI) in athymic mice (LVI) as defined by E-cadherin positive tumor emboli within lymphatic channels distinguished by podoplanin and LYVE1 membrane and Prox1 nuclear immunoreactivities and spontaneous spheroidgenesis in vitro and human cases of IBC which showed similar LVI, we compared laser-captured microdissected emboli from Mary-X as well as from cases of human IBC to non-embolic areas. Mary-X and IBC emboli expressed high levels of E-cadherin and no evidence of epithelial-mesenchymal transition (EMT). Mary-X spheroids expressed high levels of VEGF, especially VEGF-C and stimulated both vascular as well as lymphatic endothelial haptotaxis. We then transplanted Mary-X serially into green, cyano, red and nestin-green fluorescing protein (GFP-, CFP-, RFP- and nestin-GFP) transgenic reporter mice in various combinations. Multicolor murine imaging studies indicated that reporter-labelled stroma initially encircled clumps of tumor cells and then served as a scaffold which supported nestin-GFP labelled endothelial haptotaxis resulting in encircling lymphangiogenesis, confirmed by dual LYVE1 immunofluorescence. The present studies demonstrate a possible mechanism of a critical step of tumor embol.