Cycle 2 - January 2021 OEFC Research 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: Carolyn Klinge, Ph.D.
Collaborator: Matt Cave, M.D.; Xiang Zhang, Ph.D., Shesh Rai, Ph.D.
Title: Epitranscriptome in a murine model of TASH
Description: Chronic environmental exposures to polychlorinated biphenyls (PCBs) contribute to metabolic diseases including toxicant-associated steatohepatitis (TASH). Mice co-exposed to high fat diet and PCBs develop TASH, but the precise mechanisms involved in disease progression remain to be identified. There are over 160 chemical modifications of transcribed RNA that regulate transcript fate and the contribution of these modifications to the mouse liver proteome with HFD +/- PCB exposure is unknown. The objective of the proposed research is to identify global RNA modifications in C57Bl/6J male mouse liver mRNA, lncRNA, and pri-miRNA after exposure to PCB (Aroclor1260 or PCB 126) + HFD versus HFD alone (control) using mass spectrometry. Once differences in epitranscriptomic marks are identified, we will evaluate the expression of the readers, writers, and erasers of these marks to determine how environmental exposures result in different RNA epitranscriptomic modifications in liver.
CLICK HERE to view the publication that was funded in part by a CIEHS OEFC RESEARCH VOUCHER to Dr. Carolyn M. Klinge for the analysis performed in the CREAM core (headed by Dr. Xiang Zhang) to identify the global post-transcriptional chemical modification (PTM) of RNA in male mouse liver samples in a study performed in Dr. Matt Cave’s lab in which the mice were fed a HFD for 12 weeks with a single PCB exposure at the 2-week time point.
Principal Investigator: Alex Carll, Ph.D., M.S.P.H.
Collaborator: Michael Merchant, Ph.D., Petra Haberzettl, Ph.D., Daniel Conklin, Ph.D.
Title: Neural and Neuroendocrine Pathways of Airborne Toxin-Induced Cardiac Dysfunction
Description: The inhalation of airborne irritants is known to alter neural and neurohormonal regulation of the heart via the autonomic nervous system and the hypothalamic pituitary adrenal axis. These effects may in turn impair cardiac conduction, contraction, and relaxation, by impairing cardiac ion homeostasis through phosphorylation and/or de-phosphorylation of transmembrane ion channels and intracellular ion-handling proteins. This project will examine the impacts on the global cardiac phosphoproteome of inhalation exposures to three different airborne toxins with irritant properties (formaldehyde, e-cigarette aerosol, and ambient particulate matter). The data generated from this study will complement electrocardiographic data to elucidate the role of intracellular signaling and neural and neurohomormonal dysregulation in cardiac dysfunction induced by independent exposures to a diverse set of inhaled irritants.