# Defining pro-metastatic and endothelial-regulatory roles for LIN28B in hepatocellular carcinoma

> **NIH NIH K08** · UNIVERSITY OF CHICAGO · 2023 · $265,315

## Abstract

PROJECT SUMMARY
Hepatocellular carcinoma (HCC) is a lethal solid tumor that is highly dependent on recruitment of new blood 
vessels and has no common genomic targets. As for most solid tumors, metastasis causes a disproportionate 
degree of morbidity and mortality. LIN28B – an RNA-binding protein expressed in tumors and in developing 
tissues – is essential for HCC development and elevated LIN28B expression in HCC correlates with an increased 
risk of death. We recently identified LIN28B as a novel driver of pancreatic cancer metastasis and propose in 
Aim 1 to use an integrated series of molecular, cellular, and animal experiments to determine if HCC metastasis 
is driven by LIN28B. In Aim 2, I propose to couple robust co-culture (HCC cell and endothelial cell) in vitro and 
in vivo models to define how LIN28B expression in HCC cells modulates its effect on endothelial cells, which in 
turn stimulate the HCC metastatic phenotype. In Aim 3, I will utilize our expertise in novel circulating tumor cell 
purification/analysis technologies and computational analysis of conventional and novel tissue staining 
technologies to characterize the metastasis-driving and endothelial regulatory roles of LIN28B using primary 
human circulating tumor cell and tumor tissue specimens. Collectively, this work will provide functional rationale
for the development of new therapies targeting the LIN28B pathway and linked vascular-regulatory pathways in 
HCC and for the development of novel matched biomarkers. The applicant, Dr. Joseph Franses, is an oncologist 
at the University of Chicago Cancer Center. He will spend 75% of his time performing translational research and 
25% in clinical practice caring for patients with cancer. He has outlined a five-year career development plan to 
meet his goal of becoming an independent investigator in translational research. Dr. Franses has assembled an 
Advisory Committee of internationally recognized experts to provide scientific and career mentorship. He has 
established collaborations with experts in cancer genomics, molecular biology, tumor animal modeling, and 
computational biology to provide experimental advice and specific training in the field. Dr. Franses will conduct 
this research and leverage the exceptional research and teaching environment at the University of Chicago 
Cancer Center. The University of Chicago harbors an outstanding research community and has a long track 
record for successful mentorship of independent physician-scientists. This will be an ideal environment for 
successful completion of these experiments and the realization of Dr. Franses’ career goal of becoming an 
independent physician-scientist dedicated to improving the care of patients with gastrointestinal cancers.

## Key facts

- **NIH application ID:** 10865508
- **Project number:** 7K08CA263551-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Joseph Wang Franses
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $265,315
- **Award type:** 7
- **Project period:** 2023-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865508

## Citation

> US National Institutes of Health, RePORTER application 10865508, Defining pro-metastatic and endothelial-regulatory roles for LIN28B in hepatocellular carcinoma (7K08CA263551-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10865508. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*