Wednesday, December 17, 2025 12/17/2025

Causes and Consequences of Whole Genome Duplication in Cancer Progression and Acquired Drug Resistance

Award Number: R01CA279546
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/05/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

Group Awards By:

View Award Description

Causes and Consequences of Whole Genome Duplication in Cancer Progression and Acquired Drug Resistance - Summary Recent studies show that whole genome duplication (WGD) is a frequent event in cancer evolution that promotes chromosomal instability and aneuploidy. WGD tumors have worse prognosis, elevated drug resistance, and increased metastatic potential when compared with near-diploid counterparts. However, the mechanisms driving WGD during cancer evolution remain unclear. This is because the events that lead to WGD occur asynchronously and at low frequency, making them difficult to capture using traditional approaches such as fixed endpoint approaches. My lab has pioneered genetically encoded biosensors and image analysis techniques to biochemically characterize thousands of individual cells for multiple days as they go through normal or aberrant cell cycles. Using these approaches, we have found that WGD occurs in response to common stress conditions such as osmotic stress, DNA damage, and ribosome collisions. This process involves two steps: first cells go from G2 to G0 without entering into mitosis (i.e. mitotic bypass). Second, some cells escape cell cycle arrest and enter S- phase, thereby re-duplicating their genome. Furthermore, our data show that DNA damage caused by commonly used chemotherapeutics promotes WGD in cancer cells raising questions about the role of chemotherapy- induced WGD in acquired drug resistance. This is particularly important in metastatic Triple Negative Breast Cancer (mTNBC), for which DNA damaging agents are still a mainstream treatment, and the development of resistance continues to be a devastating health care problem (median survival rate <18 months). Here I propose to use our live single-cell approaches to characterize the causes and consequences of WGD in cancer progression and acquired drug resistance. In Aim 1, we will combine live cell imaging and single-cell sequencing to uncover how physiological stresses trigger mitotic bypass and WGD in non-transformed cells. In Aim2, we will study the mechanisms of chemotherapy-induced WGD in cancer cells. In Aim 3, we will use human breast cancer organoids and patient derived xenografts to define the role of chemotherapy-induced WGD in acquired drug resistance. Overall, our work will pave the way toward characterizing cell-cycle dynamics in cancer cells to identify unique vulnerabilities that target the aberrant cell cycles that drive tumorigenesis.


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: 2026 ( Subtotal = $416,314 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	000	3	12/9/2025	NON-COMPETING CONTINUATION	$416,314
														Subtotal = $416,314

Issue Date FY: 2025 ( Subtotal = $462,570 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	001	2	6/5/2025	NON-COMPETING CONTINUATION	$46,256
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	000	2	11/26/2024	NON-COMPETING CONTINUATION	$416,314
														Subtotal = $462,570

Issue Date FY: 2024 ( Subtotal = $478,340 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	000	1	12/5/2023	NEW	$478,340
														Subtotal = $478,340

Grand Total All Awards = $1,357,224

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Causes and Consequences of Whole Genome Duplication in Cancer Progression and Acquired Drug Resistance

Award Number: R01CA279546

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/05/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer