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Investigating ketogenesis as a metabolic modulator of liver regeneration

Award Number: K08DK149194
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Investigating ketogenesis as a metabolic modulator of liver regeneration - PROJECT SUMMARY/ABSTRACT This application proposes a five-year career development and research program investigating ketogenesis as a metabolic modulator of liver regeneration. The applicant, Jessica E. S. Shay, M.D., Ph.D., is an Assistant Professor of Medicine in the Division of Gastroenterology, Hepatology & Nutrition at the University of Utah. Steatotic livers regenerate poorly, yet the metabolic mechanisms underlying this dysfunction remain undefined. Prior work by Dr. Shay suggests suppression of hepatocyte ketogenesis, mediated by the enzyme HMGCS2, disrupts hepatocyte identity, promoting progressive liver dysfunction and maladaptive repair programs. The precise metabolic requirements of ketogenesis in the regenerating liver are unknown. This award will provide Dr. Shay with training in partial hepatectomy, metabolic flux analysis, mitochondrial respiration techniques, and proteome-metabolite interaction profiling. These skills will enable her to address key knowledge gaps regarding the role of ketogenesis in liver regeneration by: 1) determining whether HMGCS2 expression is necessary and sufficient for regeneration; 2) defining how ketogenesis regulates mitochondrial metabolism and nutrient flux during regeneration; and 3) identifying dietary and pharmacologic modulators of ketogenesis that alter regenerative outcomes. Targeted mentored training will ensure her transition into an independent investigator defining how metabolic pathways regulate hepatocyte adaptation and regenerative capacity in metabolic dysfunction-associated steatotic liver disease (MASLD). The five-year career development plan integrates mentored scientific and professional training to complement Dr. Shay’s background in hepatology. She will gain mechanistic expertise in stable isotope tracing (with Dr. Greg Ducker), mitochondrial energetics (with Dr. Katsu Funai), lipid biology and hormone signaling (with Drs. Scott Summers and William Holland), proteome-metabolite interactions (with Dr. Kevin Hicks), and regenerative modeling (with Dr. Kim Evason). Structured career development through the VPCAT Research Scholars Program, the Diabetes and Metabolism Research Center, and the Molecular Medicine Program will provide additional training in grant writing, leadership, and translational integration. The University of Utah offers a world-class environment for metabolism and regenerative biology, with collaborative mentorship across lipid metabolism, mitochondrial physiology, proteomics, and liver pathophysiology. The long-term goal is to equip Dr. Shay with the skills and foundation to become an independent, R01-funded physician-scientist leading a translational research program that defines metabolic vulnerabilities in MASLD and develops nutritional interventions to improve hepatocyte repair and prevent progression to advanced liver disease.


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: 2026 ( Subtotal = $174,960 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/20/2026	NEW	$174,960
														Subtotal = $174,960

Grand Total All Awards = $174,960

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Investigating ketogenesis as a metabolic modulator of liver regeneration

Award Number: K08DK149194

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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