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Investigating the mechanisms of driver genes associated with ancestry and aggressiveness in prostate cancer

Award Number: R01CA248920
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/10/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Investigating the mechanisms of driver genes associated with ancestry and aggressiveness in prostate cancer - Summary African American (AA) men have the highest incidence and mortality rate from prostate cancer in the United States. We recently showed that AA men with low-risk prostate cancer have a two-fold increased risk of death compared to men of other racial groups. While the causes of this stark disparity are multifactorial, we hypothesize that low-risk prostate cancer in AA men harbor unique genomic alterations that give rise to more aggressive prostate cancer. Towards this end, we have performed an initial meta-analysis of existing sequencing studies and found candidate driver genes associated with ancestry. However, the ability to determine the effect of these candidates on prostate cancer biology is limited due to the lack of biological cell models from different ancestral backgrounds. In Aim 1, we will find additional molecular alterations associated with grade using whole exome sequencing of prostate cancer cases from 300 AA men and 200 men from a European background using a collection of archived specimens from Boston Medical Center and UCSF. In Aim 2, we will characterize the transcriptomic and proteomic states of different prostate epithelial cell populations by performing single-cell RNA- seq and mass spectrometry of organoids derived from AA and EA men. In Aim 3, we will develop new prostate cell models from AA patients using a conditional reprogramming method. We will then perturb ancestry- and grade-associated driver genes using CRISPR/Cas9 genome editing and determine whether the functional effects of these genes are augmented in different ancestral backgrounds. At the conclusion of these studies we will have expanded our understanding of the molecular pathways are associated with aggressiveness in different ancestral backgrounds. We will also generate a large resource of prostate cell models from AA men for the scientific community to investigate prostate cancer disparities. This project will generate substantial knowledge of the mechanisms that underlie prostate cancer disparities that could ultimately lead to improved treatment of AA men with prostate cancer and the reduction of cancer health disparities.


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 = $689,827 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Biology Research	000	5	4/30/2025	NON-COMPETING CONTINUATION	$620,845
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Biology Research	001	5	5/22/2025	NON-COMPETING CONTINUATION	$68,982
														Subtotal = $689,827

Issue Date FY: 2024 ( Subtotal = $655,337 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Biology Research	000	4	4/9/2024	NON-COMPETING CONTINUATION	$655,337
														Subtotal = $655,337

Issue Date FY: 2023 ( Subtotal = $197,438 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Biology Research	000	3	7/10/2023	NON-COMPETING CONTINUATION	$197,438
														Subtotal = $197,438

Issue Date FY: 2022 ( Subtotal = $586,110 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Biology Research	000	2	4/29/2022	NON-COMPETING CONTINUATION	$586,110
														Subtotal = $586,110

Issue Date FY: 2021 ( Subtotal = $610,293 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Cancer Biology Research	000	1	5/10/2021	NEW	$610,293
														Subtotal = $610,293

Grand Total All Awards = $2,739,005

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Investigating the mechanisms of driver genes associated with ancestry and aggressiveness in prostate cancer

Award Number: R01CA248920

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/10/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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