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

Award Number: K08CA263551
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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


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: 2025 ( Subtotal = $265,315 )
2025	2025	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cancer Research Manpower	001	4	6/30/2025	NON-COMPETING CONTINUATION	$265,315
2025	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	1	2/13/2025	NEW	$0
														Subtotal = $265,315

Issue Date FY: 2024 ( Subtotal = $265,315 )
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cancer Research Manpower	002	3	7/15/2024	NON-COMPETING CONTINUATION	$265,315
2024	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cancer Research Manpower	000	2	10/23/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cancer Research Manpower	001	2	11/29/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $265,315

Issue Date FY: 2023 ( Subtotal = $265,315 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cancer Research Manpower	001	2	8/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$265,315
2023	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	1	8/21/2023	NEW	$0
														Subtotal = $265,315

Issue Date FY: 2022 ( Subtotal = $271,934 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	1	7/27/2022	NEW	$271,934
														Subtotal = $271,934

Grand Total All Awards = $1,067,879

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

Award Number: K08CA263551

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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