The Role of the Liver Receptor Homolog-1 (LRH-1) in Intestinal Epithelial Homeostasis and Cell Survival
David Moore, Professor
Nutritional Sciences and Toxicology
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Inflammatory bowel disease (IBD) is an autoimmune inflammatory condition of the gastrointestinal tract. Statistics show that the incidence of IBD in the US is around 1.3% in the adult population. The pathophysiology of IBD is multifaceted and complex, with current therapeutics requiring optimization. Genome Wide Association Studies (GWAS) and experimental evidence show that the liver receptor homolog-1 (LRH-1) is a key determinant of epithelial homeostasis, and its variants are implicated in IBD.
LRH-1 is activated and bound by the agonist phospholipid ligand - dietary dilauroyl phosphatidylcholine (DLPC), which induces anti-inflammatory effects and immunomodulating functions locally in the intestine to promote wound healing and tissue renewal in the intestine. LRH-1 is highly expressed in the crypt cells of the intestine, which are damaged in IBD patients. LRH-1 also regulates cell proliferation and differentiation in the crypts cells of the intestine. Past research has shown that increasing the expression of human LRH-1 improves TNF-alpha induced cell death, giving LRH-1 the ability to prevent intestinal damage and inflammation.
The aim of this research project is to verify the mechanism of LRH-1 activation in DSS/TNF- alpha induced colitis, and evaluate the effects of DLPC- induced LRH-1 agonism on IBD pathogenesis. Locally activating LRH-1 in the intestine and subsequent glucocorticoid production would circumvent the challenges of current IBD therapeutics (systemic steroids) and their associated adverse effects in IBD patients.
Qualifications: Students should be clear communicators and willing to work with animal models. In the laboratory, they are expected to learn/conduct molecular experiments with both in vivo and in vitro model systems, such as DNA/RNA extraction, qPCR, cell culture, genotyping and more.
Day-to-day supervisor for this project: Lindsey Fontenot, Ph.D. candidate
Hours: to be negotiated
Related website: http://nst.berkeley.edu/group/Moore-Lab
Biological & Health Sciences