# Functional Proteomic Analysis and Biomarker Identification in a Novel Mouse Model of Metastatic Hepatocellular Carcinoma (HCC)

> **NIH NIH K08** · STANFORD UNIVERSITY · 2022 · $202,144

## Abstract

Research Proposal Summary
Hepatocellular carcinoma (HCC) is a highly lethal malignancy, and is a worldwide public health problem. The
main cancer-related cause of death in patients with HCC is metastatic tumor progression. But the precise
molecular mechanisms of HCC metastasis are not well understood. Also, there are no accurate prognostic
plasma biomarkers which can help in early detection of aggressive HCC and thereby predict clinical outcome or
guide treatment selection. We have developed an autochthonous mouse model of metastatic HCC where
conditional overexpression of MYC and Twist1 genes in the mouse liver leads to step-wise progression of liver
cancer simulating human HCC. This study proposes to use this novel mouse model of metastatic HCC to explore
the mechanisms of tumor progression and identify proteomic biomarkers for HCC. Our central HYPOTHESIS is
that Twist1 modulates innate immune system specific proteomic and glycoproteomic changes which promote
metastatic progression. In Aim 1 we will perform proteomic and glycoproteomic analyses of MYC HCC and
MYC/Twist1 HCC using mass spectrometry. We will then undertake a systems biology approach to large scale
proteomics data and perform gene knockout experiments to gain mechanistic insights into how Twist1 promotes
metastasis. In Aim 2 we will identify and validate plasma proteomic and glycoproteomic biomarkers of metastatic
progression in the MYC/Twist1 mice that are relevant to human HCC. Successful completion of this study has
significant translational potential by identifying prognostic biomarkers which will improve treatment allocation.
Candidate Career Development Plan
The objective of this K08 Mentored Award application is to enable Dr. Renumathy Dhanasekaran to undertake
supervised research and career development training to become an independent physician scientist. She is a
board certified Hepatologist who joined the Department of Medicine at Stanford in 2015 and is pursuing advanced
translational research training under the mentorship of Dr. Dean Felsher. Her long term career goal is to build
an independent translational research program to identify biomarkers for HCC. This K08 will provide her with the
protected time and support needed to undertake the following training: (1) receive hands-on training in advanced
techniques in cancer biology (2) acquire skills in computational biology to perform integrated analyses of genomic
data; (3) acquire critical talents required for success in academic medicine like grantsmanship, and
communication skills and (4) gather preliminary data required to apply for a NIH R01 grant during year 4-5 of the
K08 award. The candidate has an excellent mentor with vast expertise in cancer biology and is working in a well-
funded lab. The Chief of the Division of Gastroenterology, will also serve as her co-mentor and he is personally
committed to her academic success. She has assembled a team of seasoned mentors with expertise in cancer
biology, advanced ...

## Key facts

- **NIH application ID:** 10427199
- **Project number:** 5K08CA222676-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Renumathy Dhanasekaran
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $202,144
- **Award type:** 5
- **Project period:** 2018-07-09 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427199

## Citation

> US National Institutes of Health, RePORTER application 10427199, Functional Proteomic Analysis and Biomarker Identification in a Novel Mouse Model of Metastatic Hepatocellular Carcinoma (HCC) (5K08CA222676-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10427199. Licensed CC0.

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