CLEAR & CURES Seminar feat. Dr. Ramji Bhandari (U of Missouri Columbia) - April 24, 2025 скачать в хорошем качестве

CLEAR & CURES Seminar feat. Dr. Ramji Bhandari (U of Missouri Columbia) - April 24, 2025

April 25, 2025: Dr. Ramji Bhandari, Associate Professor in the Division of Biological Sciences at the University of Missouri Columbia. Dr. Bhandari's talk is titled, "Efforts to mitigate environmentally induced transgenerational adverse health outcomes through epigenetic reprogramming of DNA epimutations ." Joint seminar by the Center for Urban Responses to Environmental Stressors (CURES) and the Superfund Research Center for Leadership in Environmental Awareness and Research (CLEAR) at Wayne State University. ABSTRACT Epigenetic inheritance of environmentally and lifestyle-induced phenotypes has been demonstrated in many model organisms in a laboratory setting, suggesting that current generations could be harboring ancestral environmental/diet exposure-induced molecular memories or future generations may carry such memories due to exposure of the current generation. Ancestral environmental exposure-related transgenerational traits may be detrimental at the population level if occurring in a natural population. It is essential to develop strategies to correct transgenerational abnormalities before they are transferred to offspring via germline transmission or to block the heritable pathways leading to the abnormal health phenotype before they induce the disease. Nevertheless, such strategies are yet to be developed. As a proof of concept, using medaka fish as an aquatic model organism of human and ecosystem health, we investigated whether the environmentally induced transgenerational non-alcoholic fatty liver disease (NAFLD) can be reversed by epigenetic modifier treatments. Ancestral bisphenol A (BPA) exposure (10 μg/L) caused transgenerational NAFLD leading to nonalcoholic steatohepatitis (NASH) in offspring at F2 generation, which persisted for five generations. The severity of the disease was sexually dimorphic- with females affected more than males. Past F2 generation, the transgenerational NAFLD started after puberty, developed in adulthood, and progressed toward NASH and fibrosis as the fish aged. We performed transcriptomic, metabolomic, and methylome analyses to understand the mechanisms involved. DNA methylation profile of the F1 paternal sperm predicted the DNA methylation and transcriptional landscape of the F2 offspring liver revealing distinct pathways associated with NAFLD. A larger percentage of transgenerational differentially methylated promoters (DMPs) present in the NAFLD liver at the F2 generation were removed in the F4 generation during germline transfer. Still, the phenotype persisted but with comparatively reduced severity. Treatment of the F4 fish with a weak epigenetic modifier resulted in: 1) A reversal of NAFLD phenotype to normal, 2) Correction of the majority of BPA-induced DMRs, irrespective of their methylation status, and 3) restoration of transcriptional network comparable to that in untreated controls. The present results suggest that low-concentration nutritional epigenetic modifiers may be useful for correcting EDC-induced transgenerational liver injury. Results open avenues for further research towards understanding the role of epigenetic landscape in metabolic health and disease and the mitigation of this multifactorial metabolic disease in humans. ABOUT THE SPEAKER Dr. Bhandari is an Associate Professor in the Division of Biological Sciences at the University of Missouri Columbia. Before joining MU, he was an Associate Professor at the University of North Carolina at Greensboro. He is a reproductive biologist by education and an environmental health scientist/epigeneticist by training. His research group investigates how gene-environment interactions lead to the development of adaptive or maladaptive phenotypic traits, mainly at the gut-liver-gonad axis. They use chemicals to which humans and non-human organisms are exposed as environment, epigenetic mechanisms as drivers, and altered health outcomes, mainly reproductive and metabolic health, as phenotypic traits. Dr. Bhandari has been supported by funding from the National Institutes of Health, the U.S. Geological Survey, the University of Missouri, and the University of North Carolina as a principal investigator. ABOUT CLEAR CLEAR is funded by the National Institute of Environmental Health Sciences of the National Institutes of Health (NIH) Superfund Research Program (SRP). The center is dedicated to understanding and mitigating adverse birth outcomes and serious developmental health problems that have been associated with urban environmental exposure to volatile organic chemicals or VOCs, a special class of pollutants found in the subsurface of post-industrial cities like Detroit MI. Sadly, Detroit has the highest preterm birth rate in the country (15.2%), and up to 37 of the 67 Superfund sites in Michigan must manage VOC contamination. Watch this video to learn more and subscribe to our channel. You can follow us on X at www.x.com/CLEARWSU and our website www.clear.wayne.edu.