COBRE in Metabolic Networks
2024 end of year report
Pictured is mouse stomach mucosa stained to detect nuclei (yellow), ghrelin (pink) and the cell membrane (cyan). From Caroline Picoli, laboratory of Ziru Li
It was a great year for the COBRE in Metabolic Networks. This report celebrates the outstanding research productivity by our COBRE group and COBRE alumni. It also amplifies the great ongoing work and the efforts of our COBRE researchers, their collaborators, our advisors and leadership, and our core facilities. Take a look at the active grant-funded projects in addition to this COBRE, and a summary of publications in 2024 from COBRE-affiliated researchers and alumni. Special thanks to our external advisors, Drs. Evan Rosen, Jacqueline Stephens, and Emily Oken, our institutional advisors, Drs. Joe Nadeau and Doug Sawyer.
This image from the Lynes lab (right) shows the amount of two different lipid molecules in red and green in mouse subcutaneous adipose tissue that were identified by the specific pattern of distribution in this tissue. Spatial lipidomics experiments such as this can identify lipid distributions in anatomical and cellular regions of complex tissues.
Left to right: Ryan Reno, Carolina Cora, Breanna Page, and Matthew Lynes
COBRE Funding
We gratefully acknowledge the Institutional Development Award (IDeA) program at the National Institute of General Medical Sciences/NIH for this support. We also appreciate institutional funding from MaineHealth, which supports our research programs, scientific resources, and training programs.
The COBRE in Metabolic Networks is in Phase 2 of funding. Annually, we receive ~$1,500,000 in direct costs and $1,080,000 in indirect costs, for a total of ~$2,580,000 coming in to MaineHealth. The allocation of funds is shown above. About 81% of the funds go towards project and scientific resource support, and the rest is for administrative support and programming. In 2024, we supported projects for Matt Lynes, Ziru Li, Isha Agarwal, and Liz Scharnetzki, and a women’s health supplement for Cara Frankenfeld. Our scientific cores are the Physiology Core (Cliff Rosen), Histopathology and Microscopy Core (Volkhard Lindner and Igor Prudovsky), and Proteomics and Lipidomics Core (Calvin Vary).
Research Return on Investment
A COBRE program is a container of research infrastructure that provides structure and holds space for advisory and mentorship networks, scientific resources, and research expertise and administration. With the support of an entire research community, our investigators thrive and go on to obtain additional research funding. In addition, new staff are hired, new students are trained, and many individuals impacted by COBRE support either stay within MaineHealth or populate the workforce within Maine and across the country.
IDeA Programs in Maine
The COBRE in Metabolic Networks joins several other Institutional Development Awards in Maine funded by the National Institute for General Medical Sciences. Our programs collaborate across the state for research, education, training, advocacy, and community partnership.
COBRE Center for Regenerative Biology and Medicine (PI: Iain Drummond PhD, MDI Biological Laboratory)
COBRE for the Study of Pain and Sensory Function (PI: Ian Meng PhD, University of New England)
COBRE in Mesenchymal and Neural Regulation of Metabolic Networks (PI: Lucy Liaw PhD, MaineHealth)
COBRE in Acute Care Research and Rural Disparities (PI: Doug Sawyer MD, PhD, MaineHealth)
COBRE in Regulation of Cellular Behavior in Response to Extracellular Cues (PI: Clarissa Henry PhD, University of Maine)
COBRE – UNE Center for Cell Signaling Research (PI: Derek Molliver PhD, University of New England)
Northern New England Clinical and Translational Research Network (PI: Cliff Rosen MD, MaineHealth and Gary Stein PhD, University of Vermont)
Maine INBRE (PI: James Coffman, MDI Biological Laboratory)
Maine INBRE External Advisory Committee Meeting in March 2024 at Southern Maine Community College. Left to right: Titus Brown (UC Davis), Lucy Liaw (MaineHealth), Story Landis (Emeritus, NINDS Intramural Research Program), Steve Fiering (Dartmouth), Sugene Noh (Colby College), Reuben Hudson (College of the Atlantic), Jennifer Honeycutt (Bowdoin College), Suzanne Angeli (UMaine), Jennifer Garcia (Univ. New England), Dustin Updike (MDI Biological Laboratory, INBRE program coordinator), Yee Mon Thu (Colby College) Jim Coffman (MDI Biological Laboratory, INBRE PI), Con Sullivan (UMaine Augusta). MaineHealth became a research partner of the Maine INBRE in 2024.
Maine at NISBRE 2024
The National IDeA Symposium of Biomedical Research Excellence is held every two years to provide a scientific forum for programs across the country. Maine and MaineHealth were well represented at the 2024 meeting in June in Washington DC.
Top row from left: Lucy Liaw, Jared Talbot, Derek Molliver, Harry Filippakis, Carolina Cora, Caroline Picoli, Tom Gridley, Ben Tero, Abby Kaija, Anne Harrington
Middle row from left: Ivette Emery, Larisa Ryzhova, Robert Wheeler, Cole Ferm, Ilka Pinz, Clarissa Henry, Jim Coffman, Iain Drummond, Ben King, Ben Harrison, Christian Potts, Tiange Feng, Peter Caradonna, Calvin Vary
Front row from left: Allie Conner, Cecile Ferguson, Sophie Craig, Christine Smith, Katie Becker, Karen Houseknecht, Becky Mountain, Denise Giuvelis, Michayla Moore
2024 Research Publications
2024 publications from COBRE-associated researchers, core directors, COBRE leadership, and alumni. COBRE-associated faculty and paper highlights are in red font, and trainees are in blue font.
Agarwal I, MacVane CZ. Shift scheduling and overnight work among pregnant emergency medicine residents. Ann Emerg Med. 2024;83(6):598-602. One in three female physicians report a pregnancy during medical training. The requirement of long hours of work, including night shift work, has negative health impact during pregnancy. This paper describes the need and opportunities to reassess parental support policies for physicians in training, and a unique program that allows pregnant Emergency Medicine residents at Maine Medical Center to avoid night shift work during vulnerable phases of pregnancy.
Al-Aly Z, Rosen CJ. Long Covid and impaired cognition - more evidence and more work to do. N Engl J Med. 2024;390(9):858-60. This review gives an overview of longer term, persistent symptoms related to SARS-CoV-2 infection, or long Covid. The focus is on studies related to neurological impact, including cognition and memory. Mechanisms of cognitive impairment may be related to fusion of neurons/glia; increased cytokine secretion and microglial activation; gut dysbiosis leading to low serotonin; endothelial inflammation and microthrombi; and impaired hypothalamic-pituitary response and low cortisol levels.
Bozadjieva-Kramer N, Shin JH, Li Z, Rupp AC, Miller N, Kernodle S, Lanthier N, Henry P, Seshadri N, Myronovych A, MacDougald OA, O'Rourke RW, Kohli R, Burant CF, Rothberg AE, Seeley RJ. Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance. JCI Insight. 2024;9(7). Circulating FGF15 is decreased in metabolic disease and obesity, leading to the question of its regulation of absorption in the small intestine, where it is produced. Using an intestinal-specific FGF15 null mouse model, this paper showed that FGF15 has an essential role in bile acid and cholesterol metabolism. These functions are independent of energy and glucose homeostasis.
Brodsky I. A new once-weekly insulin - its effectiveness and safety. N Engl J Med. 2024. Epub 20240910. doi: 10.1056/NEJMe2410551. This editorial describes the results of the QWINT-2 trial, which tested once weekly administration of insulin efsitora compared to daily insulin degludec, and found equal efficacy in decrease of glycated hemoglobin levels after 52 weeks. The treatments were also similar in percentage of time that glucose level was within target range, and also time of hypoglycemia. Efsitora is an insulin fusion protein with a single chain insulin variant and a human IgG2 Fc domain that extends its stability.
Irwin Brodsky and Gary Stein at the NISBRE meeting in June 2024 in Washington DC.
Champroux A, Tang Y, Dickson DA, Meng A, Harrington A, Liaw L, Marzi M, Nicassio F, Schlaeger TM, Feig LA. Transmission of reduced levels of miR-34/449 from sperm to preimplantation embryos is a key step in the transgenerational epigenetic inheritance of the effects of paternal chronic social instability stress. Epigenetics. 2024;19(1):2346694. This study included work performed by our Mouse Genome Modification Core facility to study changes in microRNAs that are associated with chronic social stress in males, which shows transgenerational effects in offspring. This study generated a tet-inducible miR-34c mouse for analysis of offspring behavior from male mice that experienced social instability stress.
DeMaria WG, Figueroa-Milla AE, Kaija A, Harrington AE, Tero B, Ryzhova L, Liaw L, Rolle MW. Endothelial cells increase mesenchymal stem cell differentiation in scaffold-free 3D vascular tissue. Tissue Eng Part A. 2024. Epub 20240912. Doi: 10.1089/ten.TEA.2024. 0122. A bioengineering approach was utilized to generate human mesenchymal stem cell-derived smooth muscle cells in a vascular tissue ring resembling a blood vessel. These smooth muscle cells were co-cultured with endothelial cells to mimic blood vessels in vivo, and contractile protein expression and functional strength and contraction were measured. Endothelial cells promote the formation of contractile segments with smooth muscle cells, leading to a model to study human vascular function.
DiBiase JF, Scharnetzki E, Edelman E, Reed EK, Helbig P, Rueter J, Miesfeldt S, Frankenfeld CL, Han PKJ, Jacobs EA, Anderson EC. Socioeconomic and urban-rural disparities in genome-matched treatment receipt and survival after genomic tumor testing. JNCI Cancer Spectr. 2024;8(5). This study tested whether patient socioeconomic status, education, and location of residence affected their access to cancer therapies based on genomic tumor testing. Overall, there was no disparity in patients who received genome-matched treatment, based on educational attainment, household income, or rurality, from a total sample of 1258 individuals. However, patients with lower education had worse 12 month survival compared to those with high education, and this was enhanced in groups without genome matched treatment.
The COBRE in Metabolic Networks, while housed within the Center for Molecular Medicine, has strong connections across research centers at MaineHealth. We also support innovative research within the Center for Interdisciplinary Population and Health Research. Thanks to Center Director Kevin Stein for this group image.
Ellis CPS, Tero BW, Potts CM, Malka KT, Yang X, Hamilton J, Vary C, Khalil A, Liaw L.
Cellular characteristics and protein signatures of human adipose tissues from donors with or without advanced coronary artery disease. Biomedicines. 2024;12(11). This research focused on the molecular characterization of human perivascular adipose tissue from donors undergoing open heart surgery. We compared a population with severe coronary artery disease requiring bypass surgery versus a population requiring mitral valve repair without coronary artery disease. Molecular signatures were identified via proteomics, and provided potential biomarkers in adipose tissue of coronary artery disease.
Gal J, Vary C, Gartner CA, Jicha GA, Abner EL, Ortega YS, Choucair I, Wilcock DM, Nelson RS, Nelson PT. Exploratory mass spectrometry of cerebrospinal fluid from persons with autopsy-confirmed LATE-NC. J Mol Neurosci. 2024;74(3):65. Limbicpredominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a brain pathology common in the elderly and associated with dementia. Protein profiling was performed from cerebrospinal fluid from older adults, with some having confirmed LATE-NC. A small group of proteins were identified that are statistically different in LATE-NC samples: RBP4, MIF, IGHG3 and ITM2B.
MaineHealth Institute for Research PhD graduates at University of Maine commencement in May 2024 – Marissa McGilvrey and Katie Ellis from the Liaw laboratory.
Moore M, Ryzhov S, Sawyer DB, Gartner C, Vary CPH. ALK1 signaling in human cardiac progenitor cells promotes a pro-angiogenic secretome. J Cell Signal. 2024;5(3):122-42. Human highly proliferative cells from adult epicardial cells respond to BMP9/ALK1 signaling. This study characterized the secretome induced by this pathway, and identified unique targets including sclerostin, ISLR, and IGFBP3. The secretome signature suggests a role in the stimulation of angiogenesis, which has implications for cardiac repair.
Petrelli A, Rosen CJ. Dendritic cells for Type 1 diabetes - Emerging approaches for tertiary prevention. NEJM Evid. 2024;3(7):EVIDe2400095. Type 1 diabetes has several phases of autoimmunity, where the body produces anti-islet autoantibodies, resulting in hyperglycemia and impaired pancreatic beta cell function. This review describes how dendritic cells may contribute to this pathology.
Picoli CC, Birbrair A, Li Z. Pericytes as the orchestrators of vasculature and adipogenesis. Genes (Basel). 2024;15(1). Pericytes are found as mural cells in microvessels, and also function as progenitor cells that can differentiate into other cell types. This review describes the lineage and markers of pericytes in various tissues, including adipose tissue.
Puissant MM, Agarwal I, Scharnetzki E, Cutler A, Gunnell H, Strout TD. Racial differences in triage assessment at rural vs urban Maine emergency departments. Intern Emerg Med. 2024;19(6):1733-43. This study was designed to test whether factors of perceived race and language translation needs, gender, and location affected the Emergency Severity Index and the objectivity of the emergency care triage system. Findings in urban settings were that patients perceived as non-white or female received lower acuity scores, therefore experienced longer wait times for assessment.
A ghrelin-producing cell (red) in mouse stomach mucosa. From Caroline Picoli, laboratory of Ziru Li
PhD students at NISBRE 2024 – left to right: Michayla Moore, Sophie Craig, Allie Conner, Carolina Cora
Seften LM, Scharnetzki E, Kirezi C, Craig A. Clinician stakeholder experience with telemedicine consults to assess neonatal encephalopathy in a rural state. Pediatr Neurol. 2024;160:1-7. This paper describes the impact of the Maine Neonatal Encephalopathy Teleconsultation program, a partnership between Maine Medical Center and nine community hospitals. Clinicians who participated in this teleconsultation program for neonatal encephalopathy exams were interviewed; all felt a positive benefit for care of newborns via this program.
Soucy A, Potts C, Kaija A, Harrington A, McGilvrey M, Sutphin GL, Korstanje R, Tero B, Seeker J, Pinz I, Vary C, Ryzhova L, Liaw L. Effects of a global Rab27a null mutation on murine PVAT and cardiovascular function. Arterioscler Thromb Vasc Biol. 2024;44(7):1601-16. RAB27A is of interest as a regulator of exosome secretion. A global null allele of Rab27a was generated, and the null mice showed sexdependent and age-related cardiovascular defects. Proteomic signatures of vascular tissue and perivascular adipose tissue identified impact in cardiovascular and metabolic phenotypes with loss of RAB27a.
Tharp WG, Morris CR, Santos-Ortega Y, Vary CP, Bender SP, Dixon AE. Magnitude of obesity alone does not alter the alveolar lipidome. Am J Physiol Lung Cell Mol Physiol. 2024;327(5):L615-l23. This study characterized the lipidome from bronchoalverolar lavages of individuals with a wide range of body mass indices. No differences were found based on the level of obesity, showing that obesity alone does not change the alveolar lipidome in healthy lungs.
Tsuji T, Tolstikov V, Zhang Y, Huang TL, Camara H, Halpin M, Narain NR, Yau KW, Lynes MD, Kiebish MA, Tseng YH. Light-responsive adipose-hypothalamus axis controls metabolic regulation. Nat Commun. 2024;15(1):6768. This work defined a light-responsive pathway from adipose tissue to the brain through the sympathetic nervous system. Blue-light exposure to white fat led to increased histidine circulation, activation of histaminergic neurons, and stimulation of brown adipose tissue. This activation in white adipose tissue was depending on expression of opsin3.
Basiri R, Rajanala Y, Kassem M, Cheskin LJ, Frankenfeld CL, Farvid MS. Diabetes control status and severity of depression: insights from NHANES 2005-2020. Biomedicines. 2024;12(10). This paper describes a study to assess the likelihood of depression severity based on glycemic control status using National Health And Nutrition Examination Survey data. Individuals with prediabetes versus normoglycemia did not differ in their likelihood of depression. However, individuals with diabetes had a higher likelihood of having depression compared to those with normoglycermia.
Kesharwani D, Brown AC. Navigating the adipocyte precursor niche: Cell-cell interactions, regulatory mechanisms, and implications for adipose tissue homeostasis. J Cell Signal 2024;5:65-86. PMID: 38826152; PMCID: PMC11141760. This review describes the current knowledge of adipocyte precursors and the factors that influence their self-renewal, commitment, and differentiation.
Murphy CS, DeMambro V, Fadel S, Fairfield H, Gartner CA, Rodriguez P, Santos-Ortega Y, Vary C, Reagan MR. Inhibition of Acyl-CoA synthetase long chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction. Molecular Oncology 2024, in press. Acyl-CoA synthetase long-chain family members (ACSL) are of interest in cancer, as some have been implicated in supporting fitness of multiple myeloma. Triacin C is an inhibitor of ACSL, and has significant effects on human multiple myeloma cells. This study characterizes effects of Triacin C on human multiple myeloma cell behavior and transcriptome.
Gusti Gartner and Cal Vary of the Proteomics and Lipidomics Core.
Slavin M, Frankenfeld CL, Guirguis AB, Seng EK. Use of acid-suppression therapy and odds of migraine and severe headache in the national health and nutrition examination survey. Neurol Clin Pract. 2024;14(3):e200302. Proton pump inhibitors are administered for conditions such as chronic acid reflux, stomach ulcers, and specific gut infections. This study utilized National Health And Nutrition Examination Survey data and determined that migraine or severe headache is a potential adverse event in the use of proton pump inhibitors.
Rokoff LB, Rifas-Shiman SL, Aris IM, Lin PD, Rosen CJ, Calafat AM, Gordon CM, Oken E, Fleisch AF. Mid-childhood plasma concentrations of per- and polyfluoroalkyl substances, modifiable lifestyle factors, and bone mineral density through late adolescence. Environ Sci Technol 2024;58(45):1997019980. In this study, the Project Viva cohort was used to address effects of PFAS on bone mineral density in adolescents. Bone factors were also assessed based on physical activity and dairy intake.
Di Filippo L, Rosen CJ. Latest on anabolic agents for osteoporosis treatment. Endocrinol Metabol Clin North Am 2024; 53(4):513-523. This review covers novel therapeutic strategies to treat osteoporosis, and summarizes latest clinical data of anabolic agent efficacy and side effects.
Koh EH, Ewing SK, Sigurdsson S, Gudnason V, Hue TF, Vittinghoff E, Ohlsson C, Tivesten A, Grahnemo L, Yuen T, Zaidi M, Rosen CJ, Schwartz AV, Schafer AL. Higher FSH level is associated with increased risk of incident hip fracture in older adults, independent of sex hormones. J Clin Endocrinol Metab 2024, online ahead of print.
This study tested whether baseline follicle stimulating hormone (FSH) levels predict subsequent hip fracture in older adults, using the Age, Gene/Environment Susceptibility-Reykjavik cohort. The major conclusion was that higher FSH is associated with increased risk of hip fracture.
Ziru Li and Ilka Pinz at NISBRE 2024 in Washington DC.
Kim SM, Sultana F, Korkmaz F, Rojekar S, Pallapati A, Ryu V, Lizneva D, Yuen T, Rosen CJ, Zaidi M. Neuroendocrinology of bone. Pituitary 2024; 27(6):761-777. This review covers the impact of hormonal levels in mediating bone loss, with attention to follicle-stimulating hormone, thyroid stimulating hormone, adrenocorticotropic hormone, oxytocin, prolactin, and vasopressin.
Ghosh P, Niesen MJM, Pawlowski C, Bandi H, Yoo U, Lenehan PJ, Kumar-M P, Nadig M, Ross J, Ardhanari S, O’Horo JC, Venkatakrishnan AJ, Rosen CJ, Telenti A, Hurt RT, Soundararajan V. Case-control study on post-COVID-19 conditions reveals severe acute infection and chronic pulmonary disease as potential risk factors. iScience 2024; 27(8):110406. This study addressed risk factors for long COVID using a retrospective analysis of COVID-19 patients. Chronic pulmonary disease, migraine, chronic fatigue syndrome, and fibromyalgia were identified as risk factors for long COVID.
Some of the Maine cohort at NISBRE 2024 in Washington DC.
Rosen CJ. Viral variants, vaccinations, and long Covid – new insights. N Engl J Med 2024;391(6):561562. This editorial comments on a publication (Xie Y, Choi T, Al-Aly Z. Postacute sequelae of SARSCoV-2 infection in the pre-delta, delta, and omicron eras. N Engl J Med 2024;391:515-525) geared towards understanding risk factors for developing postacute sequelae of SARS-CoV-2 (PASC) or long COVID. This study found a decrease in cumulative risk of PASC over time since start of the pandemic was due to effects related to the pandemic era and vaccines.
Liu L, Le PT, Stohn JP, Liu H, Ying W, Baron R, Rosen CJ. Calorie restriction in mice impairs cortical but not trabecular peak bone mass by suppressing bone remodeling. J Bone Miner Res 2024; 39(8):1188-1199. This study examined the effect of a 30% calorie restricted diet in 8 week old mice. Calorie restriction led to decreased bone mass and increased bone marrow adipose tissue, suggesting a shift in bone marrow stem cell lineage determination to favor adipogenesis.
Korobkina ED, Calejman CM, Haley JA, Kelly ME, Li H, Gaughan M, Chen Q, Pepper HL, Ahmad H, Boucher A, Fluharty SM, Lin TY, Lotun A, Peura J, Trefely S, Green CR, Vo P, Semenkovich CF, Pitarresi JR, Spinelli JB, Aydemir O, Metallo CM, Lynes MD, Jang C, Snyder NW, Wellen KE, Guertin DA. Brown fat ATP-citrate lyase links carbohydrate availability to thermogenesis and guards against metabolic stress. Nat Metab. 2024;6(11):2187-202. This study identifies the critical role of ATP citrate lyase (ACLY) in brown fat function. A conditional null mouse model with loss of ACLY in brown adipose tissue (BAT) led to whitening of the BAT, and cold intolerance, which is a main function of thermogenesis in BAT. Lipid metabolism and mitochondrial function were also impaired in this model. The loss of function phenotype in BAT has an overloaded TCA cycle phenotype, decline in UCP1, and metabolic imbalance.
Liu H, Liu L, Rosen CJ. PTH and the regulation of mesenchymal cells within the bone marrow niche. Cells. 2024;13(5). This review summarizes the complex role of parathyroid hormone (PTH) in bone and calcium homeostasis. PTH can promote bone formation and resorption depending on manner of administration and activities on multiple cell types in the skeletal microenvironment.
Melchiorre CK, Lynes MD, Bhandari S, Su SC, Potts CM, Thees AV, Norris CE, Liaw L, Tseng YH, Lynes MA. Extracellular metallothionein as a therapeutic target in the early progression of type 1 diabetes. Cell Stress Chaperones. 2024;29(2):312-25. Metallothionein was identified as a potential target associated with pre-diabetes, and can be secreted from pancreatic beta cells to regulate immune cell migratory responses in vitro. Inhibition of metallothionein activity in non-obese diabetic mice reduced the diabetic phenotype in this model. These data suggest metallothionein as a target in type 1 diabetes.
Celebrating successful research collaborations!
Left to right: Elena Chepurko, Sergey Ryzhov, Vadim Chepurko, Lucy Liaw, Igor Prudovsky, Volkhard Lindner
Pande S, Vary C, Yang X, Liaw L, Gower L, Friesel R, Prudovsky I, Ryzhov S. Endothelial IL17RD promotes Western diet-induced aortic myeloid cell infiltration. Biochem Biophys Res Commun. 2024;701:149552. IL17RD transduces cytokine signaling related to inflammation. In human endothelial cells, suppression of IL17RD suppressed adhesion of monocytic cells. A high fat diet model in !L17RD null mice demonstrated that loss of IL17RD decreased leukocyte infiltration into the aorta, suggesting that this pathway is relevant to obesity-related cardiovascular diseases such as atherosclerosis.
Arthur G, Poupeau A, Biel K, Osborn JL, Gong M, Hinds TD, Lindner V, Loria AS. Human soluble prorenin receptor expressed in mouse renal collecting duct shows sex-specific effect on cardiorenal function. Am J Physiol Renal Physiol. 2024;326(4):F611-F621. This paper describes a mouse model of human soluble prorenin receptor expression in the kidney collecting duct. Female mice had increased daytime blood pressure, and lack of responsiveness to angiotensin II, displaying a prohypertensive, sex-specific phenotype.
Immunfluorescence staining of CHO cells transfected with Cthrc1-myc to determine CTHRC1 intracellular localization (green). Panel on left shows nuclei stained in blue.
Korkmaz F, Sim S, Sen F, Sultana F, Laurencin V, Cullen L, Pallapati A, Liu A, Chen R, Rojekar S, Pevnev G, Cheliadinova U, Vasilyeva D, Burganova G, Macdonald A, Saxena M, Goosens K, Rosen CJ, Barak O, Lizneva D, Gumerova A, Ye K, Ryu V, Yuen T, Flolinger T, Zaidi M. Gene-dose-dependent reduction of Fshr expression improves spatial memory deficits in Alzheimer’s mice. Mol Psychiatry Nov 2024, online ahead of print. High levels of follicle-stimulating hormone (FSH) are associated with onset of Alzheimer’s disease. Mouse models have supported the ability of FSH to promote Alzheimer-like pathology. This study tested the role of FSH in memory loss, using loss of function FSH receptor mice. Major results suggest that inhibition of FSH signaling is protective for memory.
Liu L, Le PT, DeMambro VE, Feng T, Liu H, Ying W, Baron R, Rosen CJ. Calorie restriction induces mandible bone loss by regulating mitochondrial function. Bone 190:117326 Epub Nov 2024. This study addressed the effects of 30% calorie restriction on alveolar bone, using the mandible. In female mice, calorie restriction led to trabecular and cortical bone loss, associated with decreased bone formation, elevated adipogenesis, and altered ATP production rates.
Chlebek C, McAndrews C, Costa SN, DeMambro VE, Yakar S, Rosen CJ. In nondiabetic C57BL/6J mice, canagliflozin affects the skeleton in a sex- and age-dependent manner. JBMR Plus 2024;8(12):ziae128 eCollection. Canagliflozin (CANA) reduces blood glucose levels, and is used for treatment of type 2 diabetes and cardiovascular disease. This study addressed impact of CANA on bone in nondiabetic mice; skeletal benefits, especially in female mice, were found in mice with CANA treatment.
Dreyfuss JM, Djordjilović V, Pan H, Bussberg V, MacDonald AM, Narain NR, Kiebish MA, Blüher M, Tseng YH, Lynes MD. ScreenDMT reveals DiHOMEs are replicably inversely associated with BMI and stimulate adipocyte calcium influx. Commun Biol. 2024;7(1):996. This paper describes a novel analysis tool, Screen Directional MaxP test (DMT) that tests the association of circulating lipids with body mass index in humans. Two populations, with or without obesity, were studied, and lipidomics was performed on blood. 12,13 diHOME and 9,10 diHOME levels were inversely associated with body mass index. Both of these lipid species also induced calcium influx in white and brown adipocytes in vitro, suggesting that they may overlap in signaling capacity in adipocytes.
COBRE Operations
Our previous Program Manager, Cole Ferm, moved on to a new professional opportunity in 2024. I am incredibly grateful for all of Cole’s work in implementing the strategic goals of our COBRE in Metabolic Networks. In 2025, our COBRE will be supported by a new Program Coordinator, Mackenzie LaChance. Mackenzie will split her time administering this COBRE and supporting our Research Training and Education programs. We look forward to her joining our COBRE group!
Mackenzie LaChance graduated from Messiah University in December 2021. She received her bachelor’s in dance and business administration. Since then she has had a diverse background with different opportunities all helping her shape her approach to her current work. Mackenzie is excited to be a part of such a great team and company! Outside of work you can find her teaching dance at a local studio and enjoying the outdoors.
Cole Ferm, Lucy Liaw, Jackie Stephens, and Karen Houseknecht