Translational Science Oral Session II: Endocrine/Metabolism, Gastroenterology

Tuesday, April 15, 2025
3:30 pm - 4:45 pm

ROLE OF PHOSPHATIDYLETHANOLAMINE METHYLTRANSFERASE (PEMT) IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (MASH) (Endocrinology / Metabolism)
Sara Osorio-Valencia, University of Illinois Chicago
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the leading cause of chronic liver disease, affecting over 30% of the population in Western countries and up to 80% of patients with type 2 diabetes (T2D). T2D significantly increases the risk of MASLD progression to Metabolic Dysfunction-Associated Steatohepatitis (MASH), characterized by inflammation, fibrosis, and hepatocellular ballooning. Current treatments are limited to lifestyle modifications, highlighting the need to elucidate the molecular mechanisms driving MASLD/MASH progression to develop effective therapies. A hallmark of MASH is hepatic fat accumulation (steatosis), arising from an imbalance in fatty acid (FA) synthesis, storage, and utilization. FA are also incorporated into phospholipids, primarily phosphatidylcholine (PC) and phosphatidylethanolamine (PE), which are crucial for membrane integrity, and very low-density lipoprotein (VLDL) assembly and secretion. Notably, a reduced PC-to-PE ratio is consistently observed in humans and mice with MASH. This ratio is partially regulated by phosphatidylethanolamine methyltransferase (PEMT), which catalyzes the conversion of PE to PC using S-adenosylmethionine (SAM) as a methyl donor. We have previously described that hepatic PEMT expression is reduced in mice with diet-induced MASH (Lee et al., Cell. Mol. Gastroenterol. Hepatol, 2021). Furthermore, loss-of-function variants in the PEMT gene are associated with more severe MASLD and MASH in humans (Song et al., FASEB J 2005, Piras et al., Int. J. Mol. Sci, 2022).

KNOCKDOWN FAS ASSOCIATED FACTOR FAMILY MEMBER 2 PREVENTS ALCOHOL-ASSOCIATED LIVER DISEASE (Gastroenterology / Clinical Nutrition)
Zhihong Yang, Indiana University
Alcohol-associated liver disease (ALD) is a complex liver disorder resulting from excessive alcohol consumption. Fas-associated factor family member 2 (FAF2, also known as UBXD8/ETEA) is a ubiquitin ligase adaptor protein involved in endoplasmic reticulum-associated degradation (ERAD) and lipid droplet degradation.

MICROPUNCTURE-EXOSOMES DISPLAY AN ENHANCED IMMUNOANGIOGENIC PAYLOAD (Surgery)
Jazzmyn Dawes, BS, Penn State College of Medicine
Ischemia is a major cause of morbidity worldwide. The few therapeutics developed to induce angiogenesis have not found clinical translation. Exosomes, a class of small extracellular vesicles, are an emerging acellular treatment option for ischemic diseases. We recently developed an in vivo microsurgical approach, micropuncture (MP), that induces angiogenesis via targeted vascular injury possibly mediated through inflammatory paracrine mechanisms.  Our in vitro pilot studies demonstrate that MP enhances exosome (Exo) cargo. We hypothesize that MP-Exo stimulates angiogenesis via enhanced immunoangiogenic payload delivery.

APOL1 KIDNEY DISEASE VARIANTS ALTER FAT DEPOSITION IN A SEX-SPECIFIC MANNER (Endocrinology / Metabolism)
Andrew O. Kearney, BA, Northwestern UniversityObesity-which develops from environmental and biological factors-is disproportionately more prevalent among individuals of African ancestry. Part of this difference in obesity prevalence may be due to DNA variants specific to African ancestry.  Recent observational studies have reported an association between obesity and the APOL1 G1 and G2 DNA variants, common among and specific to individuals of sub-Saharan African ancestry. Compared to the G0 major allele, the G1 and G2 risk variants (RV) are known to increase the risk of kidney disease in African-ancestry patients and have been extensively studied in the renal context.

MOTIVATING CHANGE IN OLDER ADULTS: A PILOT STUDY OF MOTIVATIONAL MESSAGES TO PROMOTE QUITTING SMOKING (Geriatrics and Aging)
Adrienne L. Johnson, PhD, University of Wisconsin School of Medicine and Public Health
In the U.S., 9.7 million adults ages 60 and older smoke cigarettes and are at elevated risk for the greatest age-related fear of older adults: dementia (1-3). Compared to younger adults, older adults who smoke are half as likely to make a quit attempt, but more likely maintain abstinence using evidence-based treatments – motivational messages are necessary for this population (4-6). Previous research among older adults showed a targeted, fear-based message highlighting the risks of dementia from continued smoking significantly increased immediate motivation to quit compared to a control message (7,8).

MENTAL HEALTH SCREENINGS IN THE ED: CHRONIC TRAITS OR TEMPORARY STATES? (Diagnosis or Treatment of a Disease Process or Clinical Syndromes)
Mohammed I. Lone, UChicago Medicine
Emergency department (ED) patients demonstrate substantially higher rates of depression compared to both primary care settings and the general population. While the ED serves as a safety net for mental healthcare delivery, the clinical significance of these elevated rates remains uncertain, as mood symptoms may represent either chronic psychiatric conditions or acute stress.