APSA Journal | Spring 2021 Issue 1

SPRING 2021 • ISSUE 1

TU APSA JOURNAL

Meet the E-Board / 3-5 • Student Spotlights / 7-13 • Thank You from APSA / 13 •

TABLE OF CONTENTS About APSA

•••••••• 2

Meet the E-Board

• • • • • • 3-6

Instagram Highlights

•••••••• 6

Graduate Advisors

• • • • • • 7-8

Research Abstracts

• • • • • 9-15

Thank You from APSA

• • • • • • • 16

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ABOUT APSA

Mission Statement: The mission of Temple University Main Campus APSA is to educate undergraduates about building a career at the intersection of medicine and research, inspire students to develop the skills necessary to become active physician-scientists in healthcare and scientific advancements, and provide opportunities for networking with physician-scientists at the local, regional, and national level.

Currently, APSA aims to both help undergraduates succeed on their path to the fields of medicine and science as well as to foster a community of education, support, and discussion. This year, APSA has achieved these goals by hosting informative panels, book clubs, and member events to create a positive and educational environment.

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MEET THE E-BOARD Salma Mami

Co-President

My name is Salma, and I am a sophomore Molecular Neuroscience major with a minor in Criminal Justice.

I am a part of the Rader Lab at Penn, where my focus is on human genetics and familial hypercholesterolemia. I want to become a PhysicianScientist because I am most passionate about the intersection of research, medicine, and health inequity, and I appreciate how a lot of APSA events target these issues. An exciting thing about me is I received funding from CST to start Temple's first summer research program targeted at high school juniors in Philadelphia this summer and cannot wait to start! Some other facts about me are that I actually lived in Libya for half a year as a kid, drink too much coffee, and am EMT certified!

Naveen Gedupoori My name is Naveen. I am a sophomore Molecular Neuroscience major with a minor in Sociology of Health. I have always been fascinated by the degeneration of our brains and how people can cope with these confusing changes. It’s my goal to become a Neurologist and work with people with neurodegenerative diseases and conduct on related research in tandem with my medical practice. In my free time, I enjoy reading books, playing video games, and binging hours worth of tv at a time.

Co-President

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Julia Ting My name is Julia and I am currently a freshman Biology major with a minor in Chinese on the premed track. My current research interests include molecular/cellular mechanisms in neurometabolism and I hope to end up in the physician-scientist career field one day. A couple of my favorite things (in no particular order) include bullet journaling, coffee, cats, and doing nails. And some fun facts about me are that I am trilingual and am also an EMT!

Secretary

Fatima Umar

Neuroscience major, whose research interests are focused on reward neuroscience. School can get pretty stressful, so if it gets a bit too much and you need someone to talk to, I’m totally here; just reach out!

Treasurer

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Aleena Abbasi

Events Coordinator

My name is Aleena, and I'm a freshman biology major (CST) and public health minor on the premed track. As the Event Coordinator for APSA, I help plan and execute events that we host throughout the year. I am currently a research assistant at the Institute for Genomics and Evolutionary Medicine, and I shadow at Penn Hospital. I also love volunteering, and I currently tutor students who attend public schools in Philadelphia. Some of my hobbies include reading, playing tennis, playing the viola, and spending time with my friends and family.

I enjoy being a part of APSA as I get to meet and collaborate with others who also have an interest in research and medicine.

Madison Wolf My name is Madi, and I am a sophomore Neuroscience (CST) major with Math and German minors on the pre-med track. My research interests primarily revolve around mechanisms of neurodegeneration and neurometabolism, and I am especially interested in Alzheimer's disease. This summer I will be researching full-time in the Elrod Lab at LKSOM as well as volunteering at Temple Hospital. I also volunteer with Puentes de Salud during the school year. Some of my favorite things outside of school include cycling, cooking, photography, plants, and rabbits!

Web Coordinator

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Other E-board members not shown: Siena Wanders (STARS Representative), Chethan Reddy (Medical School Liasion)

My name is Alex and I'm currently a sophomore Biology major with a minor in Public Health in the pre-med track. I currently do research at the Fels Institute for Cancer Research where I currently study melanoma and calcium signalling. I would love to become a physician-scientist in the future as it would allow me to expand my career beyond the clinic and allow to me focus on other avenues of medicine like immunology or even health care policy. As well as focusing on my dream of becoming an interventional radiologist, I would love to hopefully continue researching in what I'm currently involved in or possibly starting anew and focusing on sickle cell anemia or LAM (lymphangioleiomyomatosis) disease. As a Social Media Chair for APSA, I help manage our Instagram page and help create cool flyers for our events. I love to be involved so as well as being of APSA, I am the Director of Media & Presentation for HLS and a PR Chair for PhiDE to name a few. In my free time, I love to read, do some photography, learn about stocks, cook, and travel/explore. A random fun fact about me is that I'm a fraternal twin.

Alexander Armstead

Social Media Coordinator

INSTAGRAM HIGHLIGHTS Check out some of the posts from this year's events!

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GRADUATE ADVISORS Daniel Jovin My name is Daniel and I am a recent Temple graduate (class of 2021, B.S. in bioengineering). I am starting my MD/PhD training at Yale School of Medicine this fall and my goal is to eventually lead my own lab while working as a physician.

I'm interested in both medical treatment and scientific research of cardiovascular disease and am eager to learn and apply interdiscplinary approaches and methods in my research. A fun fact about me is that I speak German and Romanian.

Nikkita Salla My name is Nikki and I graduated from Temple University in 2020 with a degree in Cellular&Molecular Neuroscience. As an undergrad, I did research in the Patterson lab examining neuroimmune functions in age related cognitive deficits. I currently work at the Stevens lab at the Broad Institute and Boston Children's Hospital where I am exploring neuroimmune interactions in normal brain development and in neurological disease. In Fall 2022, I will begin my PhD in neuroscience at Washington University at St. Louis.

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GRADUATE ADVISORS

Arianna Valeri My name is Arianna and I graduated from Temple in May 2020 with a double major in Neuroscience and Biology and a minor in French. At Temple, I did research in labs studying fetal neurodevelopment and bipolar disorder before becoming interested in locomotion and recovery from neurotrauma. I am currently doing research at CHOP studying bone development and healing and I recently obtained my EMT certification. I am applying MD/PhD this cycle and hope that one day my resaerch will improve the lives of people with traumatic nerve damage and congenital defects. Outisde of working, I love baking, yoga, and my rabbits.

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RESEARCH ABSTRACTS This year we asked Temple undergraduates to submit short abstracts about current research they are involved or interested in! These are some of the submissions we received.

STUDENT SPOTLIGHTS...

SHREYA SHAH JOSHUA SPRADAU MARCO GHILOTTI CHETHAN REDDY DANIEL JOVIN SIENA WANDERS

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SHREYA SHAH Shreya is a pre-medical junior undergraduate student at Temple University majoring in Biochemistry through CST and minoring in Art through Tyler, with interests in technology, biomedical sciences, and creative art. She hopes to go into clinical oncology in the future and has a passion for understanding the biochemistry of cancer. She is currently writing a paper on germline determinants of therapeutic response in cancer under Dr. Sanjeevani Arora (Cancer Prevention and Control Program) at Fox Chase Cancer Center. In her free time, Shreya enjoys painting, drawing, playing the piano and singing.

Germline vulnerabilities in DNA repair: existing and emerging therapeutic implications for precision oncology

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Shreya M. Shah 1, 2 , Elena V. Demidova 1, 3 , Randy W. Lesh 1, 4 , Michael J. Hall 1, 5 , Mary B. Daly 1, 5 , Joshua E. Meyer 6, 7 , Martin J. Edelman 8 *, and Sanjeevani Arora 1, 6 * 1 Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, 19111 2 Science Scholars Program, Temple University, Philadelphia, PA, 19122 3 Kazan Federal University, Kazan, Russian Federation, 420000 4 Geisinger Commonwealth School of Medicine, Scranton, PA 5 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, 19111 6 Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111 7 Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111 8 Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111 Authors contributed equally

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Purpose: The purpose of this review is to highlight the therapeutic relevance of germline pathogenic variants (PVs) in DNA repair genes to cancer treatments such as PARP inhibitor therapy, immune checkpoint inhibitors (ICI), and chemoradiation. Also, reviewed is emerging literature on non-canonical mechanisms that regulate DNA repair pathways that could be relevant in treatment decisions for cancer patients.

Methods: This literature review summarizes the role of germline testing in assessing cancer risk, and its impact on treatment decision. We highlight several landmark clinical trials, such as those that led to the FDA-approval of PARP inhibitor therapy for BRCA deficient tumors (germline or acquired) and tissue-agnostic FDA-approval of mismatch repair deficiency as a biomarker for ICIs. We also discuss current ongoing trials for other DNA repair genes. Also, reviewed are noncanonical mechanisms, such as VHL, SDHx, FH, ARID1A, BAP1, that are emerging as important regulators of DNA repair pathways that could be relevant when considering treatment decisions for patients carrying germline PVs in them.

Conclusion: Germline PVs in DNA repair genes are not only important for determining cancer risk but also impact treatment strategies for cancer patients. Multiple patients have benefited from the availability of treatment options specifically due to defects in DNA repair (germline or somatic).

In the future, it would be beneficial to determine if germline vulnerabilities in genes that regulate DNA repair pathways could be therapeutically exploited to design treatments that maximize patient response.

Faculty Mentor: Dr. Sanjeevani Arora, Cancer Prevention and Control Program, Fox Chase Cancer Center

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JOSHUA SPRADAU Joshua Spradau is a freshman biology major on a pre-med track at Temple University's College of Science and Technology. His goal is to practice Primary Care medicine, and he is currently working as a medical scribe at MainLine Healthcare Primary Care in Downingtown, Pennsylvania. In his free time, he enjoys playing competitive video games.

The Effect of Snowmelt on Air Pollution Levels The event of a snow shower will often leave the air smelling crisp and clean. This familiar phenomenon is caused by snowflakes’ affinities for adsorbing air pollutants, particularly car exhaust chemicals. 1 At first glance, this seems like a positive thing. However, when snow melts, the pollutants may be volatilized into the air at breathing level.

To test whether or not pollutants are released by melting snow, daily snow depth and air pollution data for Philadelphia, New York City, Seattle, Milwaukee, Denver, and Cleveland from January 1, 2009, to December 31, 2018, were gathered from the National Oceanic and Atmospheric Agency (NOAA), www.ncdc.noaa.gov, and the Environmental Protection Agency (EPA), www.epa.gov. Snowmelt magnitude was estimated by subtracting the snow depth of each day by that of the following day. The pollutants analyzed were CO (carbon monoxide), NO 2 (nitrogen dioxide), and O 3 (ozone). The AQI (air quality index) data were gathered as well. Microsoft Excel was used for the statistical analysis. Positive correlation, significant to the 99% level, was discovered between snowmelt magnitude and AQI, CO concentration, and NO 2 concentration in Philadelphia, New York City, Milwaukee, and Denver, and significant negative correlation was found in Philadelphia, New York City, and Milwaukee between snowmelt magnitude and O 3 concentration. All trends examined for Seattle and Cleveland, as well as the correlation between snowmelt magnitude and O 3 concentration for Denver, were insignificant.

These findings suggest that relationships exist between snowmelt and air pollution as two-thirds of the tested locations show statistical significance. The positive trends suggest that melting snow releases air pollutants. A possible explanation for ozone’s negative trends is that it may be adsorbed by falling snow but not volatilized back into the air following snowmelt. This could be because ozone readily dissociates into monatomic and diatomic oxygen, which would eliminate ozone from the snowpack before it melts. It is also worth noting that some of the same factors that cause snowmelt, including higher temperatures and sun exposure, also speed up the dissociation of airborne ozone, so ozone levels could be negatively correlated with snowmelt even if it is not picked up by snowfall. This research lays the groundwork for more in-depth studies that would eliminate variables such as snowflake size, snowfall duration and frequency, temperature, solar exposure, wind turbulence, and other forms of precipitation that may influence air pollution concentration.

1 Nazarenko, Y., Fournier, S., Kruien, U., Rangel-Alverado, R. B., Nepotchatykh, O., Seers P., & Ariya P. A. (2017).

Role of snow in the fate of gaseous and particulate exhaust pollutants from gasoline-powered vehicles.

Environmental Pollution, 223. https://doi.org/10.1016/j.envpol.2017.01.082

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MARCO GHILOTTI Marco G. Ghilotti is an international student from Buenos Aires, Argentina. From a very young age, Marco was forced to move around from country to country, city to city. Along the way, he learned three languages and experienced different cultures while slowly developing an interest in science. Marco is currently a senior at Temple University studying Neuroscience: Cellular & Molecular in the College of Science and Technology. During the summer of 2020, he suffered from an Epidural Hematoma caused by a car accident that sparked his interest in medicine after being in the hospital for several days. Following this traumatic event, he started becoming interested in medicine, excited to learn about physician life by shadowing and volunteering at Temple's Hospital. When Marco is not focused on school, he likes to train and compete in JiuJitsu and play Rugby for Temple. On the weekends, he enjoys going to the dog park with his puppy 'Ragnar' and drink Maté, an Argentinian tea staple of their culture.

Neuropeptide Y’s Impact on Anxiety in Female Rats Authors Ghilotti MG1, Denny RR1, Connelly KL1, Unterwald EM1,2 Affiliation Lewis Katz School of Medicine at Temple University - LKSOM 3500 N Broad St, Philadelphia, PA 19140 1Center for Substance Abuse Research – CSAR 2Department of Pharmacology Background - Anxiety activates unique mammalian brain pathways in the central nervous system (CNS) and peripheral nervous system (PNS). Neuropeptide Y and its receptors Y1 and Y2 are displayed in high abundance throughout the CNS and PNS. In rodent brains, the hypothalamus, amygdala, cortex, hippocampus, and nucleus accumbens are the key and most prolific regions in which the expression of NPY and its receptors is shown. It is understood that NPY can act as an endogenous anxiolytic. This study measured NPY and NPY Y1/Y2 receptor mRNA levels to determine if baseline anxiety among female Sprague-Dawley rats is associated with the levels of expression of this neuropeptide system.

Methods – Female rats underwent gentle handling for 8 days followed by OPF (Open Field Test) and EPM (Elevated Plus Maze Test) for the classification of two groups: “Low Anxiety” vs. “High Anxiety.” Limbic system brain regions collected included the Prefrontal Cortex (PrL), Infralimbic Cortex (IL), Nucleus Accumbens (NaC), Caudate Putamen (CPU), Basolateral Amygdala (BLA), Central Nucleus of the Amygdala (CeA), Dorsal Hippocampus (DHipp) and lastly the Ventral Hippocampus (VHipp).

Conclusion – Levels of NPY, NPY Y1, and NPY Y2 expression in the BLA were not significantly different between rats with high versus low anxiety-like behaviors

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CHETHAN REDDY My name is Chethan Reddy, and I am a sophomore Neuroscience major in the College of Liberal Arts. My career goals are to pursue a medical degree while also performing neuroscience research at either the Ph.D. level or otherwise. Outside of the classroom, I am the medical school liaison for APSA, I recently started volunteering at MANNA, and I am an undergraduate research assistant in the Wimmer lab. In my free time, I really enjoy playing basketball, pool, and piano.

Chemokine receptor antagonist RAP-103 diminishes heroin reinforcing efficacy in male but not female Sprague Dawley rats In 2017, the CDC estimated that there were 58 opioid prescriptions for every 100 people in the US alone. While opioids are considered the gold standard for pain management, emerging evidence suggests that chemokine signaling in the brain is a critical component in compromising opioidderived analgesia. Consequently, researching therapeutics that regulate the chemokine system to optimize the pain-relieving effects of opioids is pertinent. One line of research has focused on the analgesic-potentiating properties of chemokine receptor antagonists (CRAs). Prior research has established that CRAs decrease both behavioral and molecular phenotypes associated with neuropathic pain. However, limited research has explored if CRAs can modulate opioid-taking behaviors in addition to pain.

To address this gap in knowledge, The Memory, Epigenetics, and Addiction Laboratory is profiling a novel CRA: RAP-103. Adult rats underwent 16 days of heroin intravenous self-administration (0.1 mg/kg/inf). Prior to each session, animals received an injection of RAP-103 (1 mg/kg) while controls received saline. An FR1 reinforcement schedule was employed to assess heroin acquisition and a PR schedule measured motivation to acquire infusion. Males treated with RAP-103 selfadministered heroin significantly less than saline-treated controls. Moreover, RAP-103-treated males had significantly lower PR breakpoints than controls. These effects were not observed in female subjects, revealing an intriguing sexually-dimorphic effect. These results indicate that RAP103 may decrease the reinforcing efficacy of heroin in males. This work supports growing evidence that chemokine inhibition is a viable therapeutic strategy for the treatment of OUD.

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DANIEL JOVIN Daniel Jovin is a Temple senior, majoring in bioengineering with a minor in biology. He is interested in a career as a physician-scientist studying and treating cardiovascular disease and will start at an MD/PhD program in the fall. Daniel is one of the founder's of Temple's APSA chapter and is also part of Temple's Biomedical Engineering Society and Club Soccer team. Outside of school, Daniel enjoys playing and watching soccer, doing stand-up comedy, reading mafia stories, and doing sudoku.

p53 Pro72Arg polymorphism mediates HIF-dependent changes in proliferation and p21 expression in endothelial cells Daniel Jovin 1,2 , Junchul Shin 2,3 , Joon-Young Park 2,3 1 Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA 2 Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 3 Department of Kinesiology, College of Public Health, Temple University, Philadelphia, PA Contact: tug94364@temple.edu Background: P53 Pro72Arg polymorphism (P72R) is a single nucleotide polymorphism that codes for either a proline or arginine residue. P72R has been shown to determine cell growth and death under hypoxia and is associated with cardiovascular disease risk in various populations. In hypoxia and numerous other disease states, hypoxia inducible factors (HIFs) can activate p53 to control cell cycle arrest, growth, and death. P72R’s role in endothelial cells under hypoxia has not been previously studied. This project aimed to determine how P72R mediates endothelial cell cycle progression under HIF stabilization by PHD2 knockdown (KD) to understand P72R’s potential role in vascular disease.

Methods: Multiple single donor HUVECs homozygous for proline (P72) or arginine (R72) p53 were genotyped and cultured in EGM-2 (5% CO2, 37˚C). PHD2 was knocked down by siRNA transfection (50 nM). After 48 hours, protein samples were collected for Western blotting and BrdU assay and SA-β-Gal staining were performed. Two-way ANOVA with Fisher’s LSD post-hoc testing was used for statistical analysis.

Significance was set at p < 0.05.

Results: Knocking down PHD2 significantly reduced PHD2 (p = 0.01) and increased HIF-2α (p = 0.049) protein expression. PHD2 KD significantly reduced proliferation (p < 0.0001), but proliferation decreased less in R72 cells (p = 0.05). PHD2 KD also reduced cell senescence (p = 0.11) independently of P72R. Additionally, p53 expression was increased by PHD2 KD (p = 0.19) and reduced by R72 (p = 0.13) although these changes were not significant. PHD2 KD did not affect p16 expression (p = 0.47) but increased p21 expression in P72 cells (p = 0.03).

Conclusion: Pro72Arg regulates a HIF-dependent reduction in proliferation and increase in p21 expression in endothelial cells. These effects may potentially be the result of differential p53 expression levels and differential p21 activation.

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SIENA WANDERS Siena Wanders is a sophomore Biochemistry major in CST. She is a Science Scholar undergraduate researcher in the Strongin Lab working to better understand the interactions of plasmonic gold nanoparticles and ferritin. Siena aspires to enter an MD/PhD program after graduation and incorporate research into her career as a physician. In addition to undergraduate research, Siena is a registered EMT and volunteers in the emergency department at Temple University Hospital.

Computational and Experimental Analysis of Gold Nanoparticle Interactions with Wild Type Ferritins Siena Wanders, Strongin Lab The attachment of gold plasmonic nanoparticles to ferritin will allow the photochemistry of the goldferritin heterostructure to be extended to longer wavelengths of light. Metal nanoparticles, such as gold, are known to offer superior chemical stability when decorated on biomolecules, such as ferritin, a 24subunit cage-like protein with a biological function to sequester and store iron. This heterostructure is known to exhibit properties of a photocatalyst potentially useful in environmental remediation, reducing the pollutant chromate, as well as medical treatments (1). Understanding the fundamental interactions of gold nanoparticles and ferritin is necessary to further develop these systems. Using Density Functional Theory (DFT), the geometric structures, energies, and vibrational frequencies of individual amino acids, as well as short amino acid chains, found in the subunits of ferritin, were calculated and optimized using B3LYP (6-31+G). These structures were then exposed to small clusters of gold atoms in split basis set calculations (6-31+G and Def2TZVP), to calculate the binding energy and observe any preferential interactions of the gold atoms to the amino acids.

Complimentary experimental work was completed by combining synthesized gold nanoparticles and wild type ferritins, both horse spleen (primarily L-chain) and solely H-chain, to observe interactions.

Absorption spectroscopy was used to track deviations in the surface plasmon resonance of the gold nanoparticles. This shift indicates changes to the area surrounding the nanoparticle from ferritin binding on both short (minutes to hours) and long (days to weeks) timescales. Key aspects of the UV-VIS spectra that indicate gold-ferritin binding were determined through comparison. Different capping agents, stabilizers that inhibit over-growth and prevent aggregation such as citrate and ascorbate, were compared. Ascorbate-capped gold nanoparticles proved to be more easily displaced by cysteine and ferritin compared to the citrate-capped gold nanoparticles. Additionally, capitalizing on the known affinity of gold and sulfur, absorption spectra of cysteine, an amino acid with a sulfur-containing thiol group, and gold nanoparticles were taken to compare with absorption spectra of gold nanoparticles and ferritin. These spectra exhibited strong, concentration dependent shifts in the gold nanoparticle surface plasmon resonance (2). Horse spleen ferritin consists of 90% L-chain and 10% H-chain with about 1 cysteine per subunit in the pore of the protein, whereas wild-type H-chain ferritin consists of about 3 cysteines per subunit with 2 cysteines that are surface exposed. H-chain ferritin expectedly produced spectra that indicated increased gold-ferritin interaction resembling the interactions of gold nanoparticles and cysteine. Samples were additionally analyzed with transmission electron microscopy (TEM) to visually identify gold nanoparticle and ferritin heterostructures. By combining computational and experimental results, a more complete picture of ferritin-gold interactions was determined.

References: 1. Cerkez, E. Dutton, K. Photochemistry of ferritin decorated with plasmonic gold nanoparticles.

Environ. Sci.: Nano, 2019, 6, 85-93.

2. Mocanu, A. Cernica, I. Self-assembly characteristics of gold nanoparticles in the presence of cysteine. Colloids Surf, A Physiochem Eng Asp., 2009, 338, 93-101.

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THANK YOU FROM APSA

This past year has been challenging and unfamiliar in more ways than one, but it is because of you that APSA has been able to grow as an organization and continue its mission of guiding Temple undergraduates. Despite having to adjust to the circumstances we are living in, we have been able to host a number of new events over the 2020-2021 school year, including virtual sociology book club meetings, informative panels featuring special guests, and even our first game night for members. We have had a lot of fun engaging with you and seeing how you have been able to succeed, and we hope you have enjoyed spending time with us as well. We wish you all the best of luck wherever you are headed next, and if you are returning for the 2021-2022 school year, we cannot wait to see you again. From all of us at APSA, thank you!

16 This journal was created by Madison Wolf and Aleena Abbasi.