# Hepatic metabolic reprogramming drives pancreatic cancer cachexia

> **NIH NIH K08** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $247,925

## Abstract

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.

## Key facts

- **NIH application ID:** 10210248
- **Project number:** 5K08CA245188-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Aaron Grossberg
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $247,925
- **Award type:** 5
- **Project period:** 2020-07-03 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210248

## Citation

> US National Institutes of Health, RePORTER application 10210248, Hepatic metabolic reprogramming drives pancreatic cancer cachexia (5K08CA245188-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10210248. Licensed CC0.

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