Sunday, August 31, 2025 8/31/2025

Regulation of RBP Function during EMT

Award Number: R01CA277495
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

Group Awards By:

View Award Description

Regulation of RBP Function during EMT - The goal of this research is to characterize Ras-driven and KSR1-dependent mechanisms that modulate tumor initiation, drug resistance and the epithelial-to-mesenchymal transition (EMT) in colorectal cancer. Tumor initiating cells (TICs) are a subpopulation of tumor cells defined by their ability to self-renew and regenerate the entire heterogeneous tumor population and are believed to be a reservoir of drug resistant persister cells. EMT- like behavior contributes to tumor initiation, invasion, and metastasis. Partial reversal of EMT to a “hybrid” state is necessary for efficient TIC formation and metastatic colonization. In turn, TICs lose clonogenicity and self- renewal and acquire the invasive behavior of mesenchymal cells that drives their dissemination. While the interconversion of tumor cells to migratory and invasive mesenchymal cells from self-renewing TICs is necessary for metastasis, little is known about the mechanisms that direct tumor cells between these phenotypes. We combined targeting of genes encoding key effectors of Ras signaling with polysome profiling and computational analysis to discover that the molecular scaffold KSR1 mediates resistance to clinically approved drugs and regulates TIC formation and EMT via RNA binding protein SRSF9. Our preliminary data suggest the hypothesis that KSR1- dependent signaling in KRAS-mutated CRC promotes the splicing and translation of mRNAs critical to CRC tumor initiation, drug resistance, and EMT. Using genetically modified CRC organoids, mouse models, and cells, the synergistic expertise of our team will characterize these novel pathways controlling CRC behavior in vitro and in vivo by 1) Characterizing the KSR1-dependent pathway(s) necessary for tumor initiation and resistance, 2) Defining the KSR1-dependent mechanism(s) driving cells from partial EMT toward invasive mesenchymal behavior, and 3) Determining how KSR1-dependent splicing promotes translation of proteins critical for EMT. Completion of this research will reveal novel mechanisms that may be targeted to improve therapeutic response and inhibit tumor initiation and metastasis.


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 = $420,208 )
2025	2025	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Cancer Biology Research	001	2	5/22/2025	NON-COMPETING CONTINUATION	$42,020
2025	2025	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Cancer Biology Research	000	2	4/11/2025	NON-COMPETING CONTINUATION	$378,188
														Subtotal = $420,208

Issue Date FY: 2024 ( Subtotal = $433,583 )
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Cancer Biology Research	000	1	4/30/2024	NEW	$433,583
														Subtotal = $433,583

Grand Total All Awards = $853,791

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation of RBP Function during EMT

Award Number: R01CA277495

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer