In this R01 proposal, we plan to use an integrative genomics (Omics) analysis to test two central hypotheses: 1) an environmental or cellular stimulus such as hormones induced distinct chromatin interacting foci such as enhancer-enhancer looping foci play key roles in regulating cell transformed phenotype; and 2) 3D chromatin structures play key roles in governing cell identities. The ultimate goal is to dissect the relationship between chromatin interactions and cell identities or cellular phenotypes. Using a model system of ER? in breast cancer, we will a) identify distinct types of ER?-regulated chromatin interacting foci including promoter- enhancer, enhancer-enhancer and enhancer-repressor looping foci; and b) identify 3D-regulated breast cancer cell identities and sensitive-resistant transition cell subpopulations. The successful completion of our proposed studies will be of value to the genomics community and biologists in general, which may result in the better understanding of the contribution of enhancer-enhancer interacting network towards functions of various biological processes, in particular breast cancer endocrine resistance, and on how 3D chromatin structure governs the breast cancer sensitive cell subpopulations into resistant cell subpopulations.

Public Health Relevance

Using a model system of ER? in breast cancer, we will a) identify distinct types of ER?-regulated chromatin interacting foci including promoter-enhancer, enhancer-enhancer and enhancer-repressor looping foci; and b) identify 3D-regulated breast cancer cell identities and sensitive-resistant transition cell subpopulations. The successful completion of our project may result in the better understanding of the contribution of enhancer- enhancer interacting network towards to functions of various biological processes, in particular breast cancer endocrine resistance, and on how 3D chromatin structure governs the breast cancer sensitive cell subpopulations into resistant cell subpopulations.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM114142-05A1
Application #
10154162
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Phillips, Andre W
Project Start
2015-04-13
Project End
2024-11-30
Budget Start
2020-12-10
Budget End
2021-11-30
Support Year
5
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Texas Health Science Center
Department
Genetics
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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