Wednesday, July 2, 2025 7/2/2025

Mechanisms of cell proliferation in whole-genome doubled cells

Award Number: R01CA274743
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2025

Group Awards By:

View Award Description

Mechanisms of cell proliferation in whole-genome doubled cells - Unscheduled whole-genome doubling events (WGD) give rise to polyploid cells that are associated with human disease. Most significantly, WGD generates genetically unstable tetraploid cells that can fuel tumorigenesis. Recent computational analyses have revealed that nearly 40% of all solid tumors have undergone at least one WGD, often early in their development, demonstrating that such events play significant roles in both the initiation and/or progression of human malignancies. Gaining a comprehensive understanding of the mechanisms through which whole-genome doubled cells arise and promote tumorigenesis is therefore a critical, albeit largely unexplored area of cell biology. The goal of this proposal is to combine computational, cell biological, and animal model methodologies to test the overarching hypothesis that whole genome-doubled cells must acquire specific genetic adaptations that enable them to tolerate the numerous defects imparted by doubled DNA content, and that these cells are therefore imparted with specific genetic dependencies that are not present in normal diploid cells (i.e. ploidy-specific lethality). These hypotheses will be tested in three specific aims. Aim 1: Use an innovative approach to rapidly quantitate the frequency and underlying cause of WGD in different tissues in vivo and determine if this frequency is affected by aging. Aim 2: Validate KIF18A, which encodes for a mitotic kinesin, as a ploidy-specific lethal gene in vivo, and use isogenic diploid/tetraploid cell models to perform an imaging- based phenotypic screen to identify small molecule inhibitors of KIF18A. Aim 3: Identify genetic aberrations (e.g. gene amplifications/deletions) that are significantly and specifically enriched in whole genome-doubled tumors, and mechanistically define how such alterations provide ploidy-specific growth advantages in vitro and in vivo. Successful completion of these aims will provide significant insight into the genesis, biology, and evolution of whole-genome doubled cells, as well as potentially reveal new and innovative therapeutic avenues to selectively kill whole-genome doubled cancer cells while sparing the normal healthy diploids from which they arose.


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 = $443,434 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Centers Support Grants	001	4	5/22/2025	NON-COMPETING CONTINUATION	$44,343
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Centers Support Grants	000	4	3/21/2025	NON-COMPETING CONTINUATION	$399,091
2025	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Cause and Prevention Research	002	3	5/27/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $443,434

Issue Date FY: 2024 ( Subtotal = $556,565 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Centers Support Grants	000	3	4/24/2024	NON-COMPETING CONTINUATION	$480,160
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Cause and Prevention Research	001	3	4/26/2024	SUPPLEMENT FOR EXPANSION	$76,405
														Subtotal = $556,565

Issue Date FY: 2023 ( Subtotal = $602,827 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Centers Support Grants	000	2	4/28/2023	NON-COMPETING CONTINUATION	$536,499
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Cause and Prevention Research	001	2	9/15/2023	SUPPLEMENT FOR EXPANSION	$66,328
														Subtotal = $602,827

Issue Date FY: 2022 ( Subtotal = $426,814 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Centers Support Grants	000	1	4/22/2022	NEW	$426,814
														Subtotal = $426,814

Grand Total All Awards = $2,029,640

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of cell proliferation in whole-genome doubled cells

Award Number: R01CA274743

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer