Thursday, November 21, 2024 11/21/2024

Diversity supplement to P01CA240685 to characterize bromodomain proteins associated with endocrine therapy resistance in breast cancer

Award Number: P01CA240685
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Gary Stein and Janet Stein, Program Directors Our Program Project is a thematically, experimentally and operationally integrated multidisciplinary team approach to address key components of genome organization that are functionally linked to modified epigenetic control of gene expression in breast cancer. The thematic focus and working hypothesis of our Program is that genomic organization and epigenetic control of gene expression coordinately facilitate physiological regulation, including hormone responsiveness, of normal and cancer cell growth, proliferation and cell identity. Our highly collaborative research team established paradigm-shifting insights into parameters of nuclear organization that include: 1. Mitotic gene bookmarking by phenotypic transcription factors to control fidelity of gene expression as cells divide; 2. Relationships between fidelity of nuclear organization, transcription factor localization and metastasis of breast cancer to bone; 3. Dynamic modifications of higher-order inter- and intra-chromosomal interactions in breast cancer cells; 4. Coordinate control of cell growth and phenotype by tissue-specific transcription factors; 5. Epitranscriptomic profiling of endocrine therapy resistant and advanced breast cancer cells in response to selective estrogen receptor modulators; and 6. Noncoding RNA-mediated regulation of the aggressive breast cancer phenotype. This application captures the scientific progress, synergy and momentum of our research team and leverages powerful new technologies for editing the genome, visualizing cells at super resolution and in real time, and decoding higher-order genome organization. We will use normal mammary epithelial, subtype-specific and endocrine resistant breast cancer cell models for discovery, then validate key findings and examine potential clinical relevance using animal models, public databases and patient tumor specimens and organoids. Emphasis will be on exploring molecular mechanisms that integrate multiple dimensions of epigenetic control with modified genome organization in breast cancer. Each of the three projects focuses on a unique aspect of epigenetic control that is required for fidelity of gene expression and is compromised in breast cancer, including: the pivotal role of mitotic gene bookmarking in stabilizing the normal mammary epithelial phenotype (Project 1); novel functions of bromodomain chromatin readers in endocrine therapy resistance (Project 2); and contributions of the novel long noncoding RNA MANCR to deregulated genome organization in aggressive breast cancer (Project 3). A shared resource core will support integrated bioinformatics and biostatistics analyses; standardized experimental design; cell, organoid and in vivo models; and resource authentication to ensure scientific rigor and reproducibility. An administrative core will maximize scientific and programmatic integration, prioritization and oversight. The impact of this program will be the integration of multiple levels of genome organization and of epigenetic control to understand how gene regulation is disrupted in breast cancer.


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: 2024 ( Subtotal = $1,749,736 )
2024	2024	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Cause and Prevention Research	002	4	7/1/2024	NON-COMPETING CONTINUATION	$0
2024	2024	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Cause and Prevention Research	000	4	4/11/2024	NON-COMPETING CONTINUATION	$1,679,239
2024	2024	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Cause and Prevention Research	003	4	8/15/2024	NON-COMPETING CONTINUATION	$0
2024	2024	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Cause and Prevention Research	004	4	9/5/2024	SUPPLEMENT FOR EXPANSION	$70,497
2024	2023	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Cause and Prevention Research	001	3	6/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,749,736

Issue Date FY: 2023 ( Subtotal = $1,734,873 )
2023	2023	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Cause and Prevention Research	000	3	4/3/2023	NON-COMPETING CONTINUATION	$1,734,873
														Subtotal = $1,734,873

Issue Date FY: 2022 ( Subtotal = $1,734,864 )
2022	2022	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Cause and Prevention Research	000	2	4/11/2022	NON-COMPETING CONTINUATION	$1,734,864
														Subtotal = $1,734,864

Issue Date FY: 2021 ( Subtotal = $1,678,923 )
2021	2021	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT ST	BURLINGTON	VT	05405	CHITTENDEN	USA	Cancer Cause and Prevention Research	000	1	3/30/2021	NEW	$1,678,923
														Subtotal = $1,678,923

Grand Total All Awards = $6,898,396

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Diversity supplement to P01CA240685 to characterize bromodomain proteins associated with endocrine therapy resistance in breast cancer

Award Number: P01CA240685

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer