Cycle 5 - December 2021 Ready to Go OEFC Voucher Awards

Medium OEFC Research Voucher Award(s):Medium research voucher applications support the expenses (up to $5,000) associated with critical exploratory research and proof-of-concept studies needed by CIEHS members for hypothesis generation and grant (re-) submission.

Principal Investigator: Venkatakrishna Jala, Ph.D.
Collaborator: Matthew Cave, M.D.
Title: Combating environmental toxin, PCB-126 associated toxicities
Lay Description: Polychlorinated biphenyls (PCB) are environmental toxins and are associated with numerous cancers, skin lesions, thyroid disruption, and altered menstrual cycling, as well as damage to the nervous, immune, and cardiovascular systems. We found that exposure of one such PCB called ‘PCB-126’ caused significant damage to in intestinal epithelial barrier. We identified that co-treatment beneficial dietary microbial metabolite called ‘urolithin A (UroA)’ rescued PCB-126-mediated intestinal epithelial barrier damage. The goal of this project is to identify molecular mechanisms responsible for UroA-mediated protective activities against PCB-126-induced toxicities. We proposed to perform RNA-sequencing experiments to determine the regulation of differential gene expression in intestinal epithelial organoids that were exposed to PCB-126 in the presence or absence of UroA.

Principal Investigator: Carolyn Klinge, Ph.D.
Collaborator: Matthew C. Cave, M.D., Yan Li, M.D., Ph.D., Xiang Zhang, Ph.D.
Title: Epitranscriptome in a murine model of diet and PCB-induced HCC
Lay Description: This project will identify chemical modifications on transcribed RNA in the livers of male mice on a low-fat diet with or without a single exposure to a mix of polychlorinated biphenyls (PCBs). These chemical changes on RNA are the ‘epitranscriptome’. Some of the mice in this study developed hepatocellular carcinoma (HCC) and we will identify the transcriptome in the HCC tumors. We will use computational analysis to identify cellular pathways altered in these samples.

Principal Investigator: J. Christopher States, Ph.D.
Collaborator: Juw Won Park, Ph.D.
Title: Gene Fusions and In/del Mutations in Arsenic-induced Skin Cancer
Lay Description: Recent research has revealed that gene rearrangements resulting in formation of ‘hybrid genes’ (aka ‘gene fusions’) are driving carcinogenesis. Arsenic exposure is known to cause chromosomal instability and gene rearrangements. This research voucher will allow us to examine genomic DNA isolated from a few arsenic exposure induced skin tumors for evidence of deletions in genes and rearrangements of genes that may be causing the cancer formation.

Principal Investigator: Banrida Wahlang, Ph.D.
Collaborator: Carolyn Klinge, Ph.D., Matthew C. Cave, M.D.
Title: Alterations in gut microbiome caused by long-term exposure to PCBs
Lay Description: Polychlorinated biphenyls (PCBs) are environmental chemicals that have been linked to numerous health effects in people who are exposed to them. These health effects include liver disease, reproductive defects, and cardiovascular diseases. Our gut bacteria play an important role in influencing liver health with higher amounts of "good bacteria" known to be beneficial to the liver. PCBs are known to cause changes to gut bacteria composition, and this may potentially promote liver diseases. Using experimental models in the laboratory, extensive research has been performed on how PCB exposures, over shorter periods of time, can cause toxicity to organs such as the liver and gut. However, little is known on how PCB exposures over longer periods of time can impact these organs. The proposed project seeks to understand how long-term exposures to PCBs can affect the composition of gut bacteria in the body, and how these changes can, in turn, impact liver health and/or worsen liver disease. Importantly, people are exposed to "forever chemicals" such as PCBs over their life span, therefore these long-term exposure studies are relevant because they better reflect human exposure patterns.

Principal Investigator: Kupper Wintergerst, MD
Collaborator: Lu Cai, M.D., Ph.D., Yi Tan, Ph.D., Sara Watson, M.D.
Title: Serum nonessential and essential metals in children with type 1 & type 2 diabetes
Lay Description: Our study will investigate the connection between diabetes and the presence or absence of essential and toxic metals in children and adolescents with type 1 or type 2 diabetes. Essential metals, such as zinc or calcium, are important to normal body function. Toxic metals, such as lead or arsenic, can be dangerous. Our goal will be to determine if there is an association between having high or low quantities of these metals and the diagnosis of diabetes.