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The impact of bile acid homeostasis on hepatic xenobiotic receptors

Award Number: F31DK122725
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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The impact of bile acid homeostasis on hepatic xenobiotic receptors - PROJECT SUMMARY/ABSTRACT Fibroblast growth factor 15 (Fgf15) is the mouse ortholog of human FGF19. FGF15/19 are endocrine FGFs produced in the distal small bowel that govern whole-body homeostasis through the regulation of bile acids, hepatic glucose, and lipid metabolism. Recognizing the pleotropic role of FGF15/19 in regulating hepatobiliary function, pharmaceutical companies have launched research programs testing the therapeutic potential of FGF19 to treat numerous liver and metabolic diseases. Nonalcoholic steatohepatitis (NASH) is a disease that has been characterized by the disregulation of many of the metabolic pathways governed by FGF19. NASH is rapidly becoming a major health issue in the United States as it affects approximately 3-12% of the population. There are currently no pharmaceutical therapies for NASH patients. NASH is projected to overtake hepatitis C virus as leading indication of liver transplant in the United States. The bile acid-FXR- FGF15/19 pathway is being investigated for its potential for use as a therapeutic intervention of NASH, with FGF19 protein functioning as a prospective treatment. Our preliminary data suggests that FGF19 protein alters drug-metabolizing enzymes. Alterations to drug-metabolizing enzymes can lead to drug-drug interactions, in which a perpetrator drug alters the disposition and/or action of a victim drug when taken in combination. Drug-drug interactions can lead to the loss of efficacy or toxicity in patients, therefore it is important to properly evaluate the potential of new therapies to alter drug-metabolizing enzymes. The research aims in this proposal will investigate the potential of FGF15/19 to bring about changes in drug- metabolizing enzymes. Aim 1 will descriptively characterize the observed variations and delineate the role of specific xenobiotic receptors. In addition, we will examine whether or not the observed changes in drug- metabolizing enzymes from our preliminary data affect the rate at which probe substrates are metabolized. Aim 2 will use in vitro and in vivo methodologies to elucidate the mechanism by which these changes are induced. Through the completion of the research and training described in this F31 Fellowship, the Principal Investigator will be trained in basic and translational biomedical research and will be prepared to conduct independent research, which is in line with the mission and vision of the National Institute of Diabetes and Digestive and Kidney Diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	1/19/2023	NON-COMPETING CONTINUATION	$0
2023	2019	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/19/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $31,139 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/17/2020	NON-COMPETING CONTINUATION	$31,139
														Subtotal = $31,139

Issue Date FY: 2019 ( Subtotal = $30,635 )
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/8/2019	NEW	$30,635
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	5/8/2019	NEW	$0
														Subtotal = $30,635

Grand Total All Awards = $61,774

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The impact of bile acid homeostasis on hepatic xenobiotic receptors

Award Number: F31DK122725

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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