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Your Environment. Your Health.

ARSENIC'S EFFECTS ON THE INTESTINAL STEM CELL NICHE

Export to Word (http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R15ES031766&format=word)
Principal Investigator: Bain, Lisa J
Institute Receiving Award Clemson University
Location Clemson, SC
Grant Number R15ES031766
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 01 Feb 2021 to 31 Jan 2024
DESCRIPTION (provided by applicant): 7. Project Summary/Abstract Arsenic is a contaminant found in drinking water and food, resulting in the exposure of millions of people to concentrations above the current US EPA and WHO drinking water standard. Evidence from epidemiological studies has demonstrated that in utero, childhood, and adult exposure to arsenic is associated with reduced birth weight and weight gain, although the mechanisms responsible are not well understood. In addition, even though ingestion is the main route of arsenic absorption, almost nothing is known about the effects of arsenic on the small intestine itself. Our lab has conducted pilot studies exposing intestinal organoids to arsenic, and found that exposure reduces stem cell differentiation and inhibits production of specific adult cell types. Thus, the goal of this application in to assess the time course, the persistence of the phenotype, the mechanisms behind this loss of differentiation, and whether a similar loss of differentiation happens to the intestinal epithelium in vivo. In the first aim, we determine the dose-response, assess whether arsenic and its mono- and di-methylated metabolites are equivalently toxic, and assess the mechanisms responsible for aberrant differentiation, including changes in apoptosis, proliferation, and cell signaling. In the second and third aim, we will ascertain whether intestinal niche function, stem cell differentiation, and function is impaired during an in vivo arsenic exposure. We will also study the role of mesenchymal cells in maintaining the niche. These studies will further our understanding of how arsenic alters cellular differentiation and reduces growth. More importantly, our research will determine whether exposed populations can ever ‘recover’ from an arsenic exposure
Science Code(s)/Area of Science(s) Primary: 17 - Stem Cell Biology and Cellular Differentiation
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications See publications associated with this Grant.
Program Officer Carol Shreffler
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