This grant application aims to understand basic biology of prostate epithelial differentiation. Mammalian tissues are composed of cells organized in a hierarchical manner, including stem cels, committed progenitors, and terminally differentiated cells. Dissecting the tissue lineage hierarchy will help identify molecular signaling pathways that play key roles in development and diseases. The prostate epithelial lineage hierarchy remains largely undefined. Though two distinct types of multipotent prostate stem cells have been identified, it remains unclear how stem cells differentiate and generate terminally differentiated cell lineages. This grant proposal is focused on the general question of how prostate stem cells give rise to prostate luminal epithelial cells that constitutes more than 90% of prostate epithelia. Our goals are to investigate how the prostate luminal cell lineage is sustained and what the roles are of the androgen receptor in different epithelial cell lineages along epithelial cell differentiation. Our preliminary data suggest that luminal cells are phenotypically and functionally heterogeneous and support the long-existing hypothesis of the existence of a population of androgen- independent prostate luminal progenitors. Using a combination of genetic and cellular approaches, we will (1) determine how the prostate luminal cell lineage is sustained in vivo;(2) isolate prostate luminal progenitor cells based on their antigenic expression profiles;(3) investigate the biological role of the androgen receptor in different prostate epithelial cell lineages.

Public Health Relevance

Prostate related diseases, including benign prostatic hyperplasia and prostate cancer, represent major health problems for men. Our proposed studies are important prerequisites to unveil molecular signaling pathways that play critical roles in initiation and progression of these diseases, and will eventually have a major impact on their diagnosis and therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK092202-02
Application #
8339460
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Hoshizaki, Deborah K
Project Start
2011-09-27
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$340,388
Indirect Cost
$122,888
Name
Baylor College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030