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Hepatic metabolic reprogramming drives pancreatic cancer cachexia

Award Number: K08CA245188
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/03/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Hepatic metabolic reprogramming drives pancreatic cancer cachexia - PROJECT SUMMARY Cachexia is a devastating complication of pancreatic ductal adenocarcinoma (PDAC) defined by loss of lean mass out of proportion to the caloric deficit. Cachexia is a major determinant of both lifespan and quality of life in patients with PDAC. The mechanisms underlying this catabolic state are poorly understood, and there remain no effective treatments. We have recently found that PDAC alters the regulation of metabolic genes in the liver, the organ that controls whole-body physiology in response to nutrient availability. The metabolic program reflects high energy availability in the livers of cachectic mice, suggesting a mismatch between hepatic nutrient sensing and availability. In this proposal we will investigate the role of this hepatic metabolic reprogramming on PDAC-associated cachexia. In Aim 1 we will modulate the hepatic activity of mTOR, a nutrient-sensing kinase that controls liver metabolism, to demonstrate that modification of hepatic nutrient sensing impacts tissue wasting. In Aim 2 we will investigate the effect of PDAC on nutritive and circadian regulation of liver metabolism and explore human samples for coherent effects. These Aims will provide fundamental insight into the deregulation of hepatic metabolism by PDAC, its role in cancer cachexia, and the circulating signals that mediate these changes. My goal is to become a successful independent physician-scientist investigator and a leader in the field of cancer metabolism, with the long-term goals of identifying new therapeutic targets to improve lifespan and quality of life in cancer patients. During this mentored career development award, I will receive excellent mentorship from Dr. Rosalie Sears, a leader in pancreatic tumor biology and Director of the Brenden-Colson Center for Pancreatic Care. I will undertake additional training in the field of hepatic metabolism, with guidance from Dr. Markus Grompe, and cachexia physiology, under the tutelage of Dr. Daniel Marks.


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 = -$24,670 )
2026	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	000	5	11/28/2025	NON-COMPETING CONTINUATION	-$24,670
														Subtotal = -$24,670

Issue Date FY: 2024 ( Subtotal = $200,031 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	000	5	7/30/2024	NON-COMPETING CONTINUATION	$200,031
														Subtotal = $200,031

Issue Date FY: 2023 ( Subtotal = $247,925 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	000	4	7/7/2023	NON-COMPETING CONTINUATION	$247,925
														Subtotal = $247,925

Issue Date FY: 2022 ( Subtotal = $247,925 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	000	3	7/19/2022	NON-COMPETING CONTINUATION	$247,925
														Subtotal = $247,925

Issue Date FY: 2021 ( Subtotal = $247,925 )
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	000	2	6/21/2021	NON-COMPETING CONTINUATION	$247,925
														Subtotal = $247,925

Issue Date FY: 2020 ( Subtotal = $247,925 )
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	000	1	7/3/2020	NEW	$247,925
														Subtotal = $247,925

Grand Total All Awards = $1,167,061

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Hepatic metabolic reprogramming drives pancreatic cancer cachexia

Award Number: K08CA245188

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/03/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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