A Chemical Approach to Stem Cell Biology
Grant Award Details
Grant Type:
Grant Number:
RS1-00302
Investigator(s):
Human Stem Cell Use:
Award Value:
$748,944
Status:
Closed
Progress Reports
Reporting Period:
Year 2
Grant Application Details
Application Title:
A Chemical Approach to Stem Cell Biology
Public Abstract:
The aim of this project is to screen large collections of small molecules to identify molecules that allow one to propagate human embryonic stem cells (hESCs) in cell culture under defined conditions in an undifferentiated, pluripotent state. The chemical structures of any biologically active small molecules will be optimized with respect to potency, selectivity and biological stability. The ability of hESCs proliferated in the presence of such small molecules to be differentiated into specific cell lineages both in cell culture and in vivo will also be assessed. And finally, we will determine the mechanism of action of active small molecules by a variety of biochemical and genomic methods. The demonstration that one can identify synthetic drug-like molecules that allow one to control the self-renewal and/or differentiation of hESCs will represent an important step in the ultimate therapeutic application of hESCs to human disease. In addition, biological studies of such molecules should provide new insights into the processes that control stem cell biology.
Statement of Benefit to California:
Historically, small molecules have been more useful than genetic approaches in the treatment of human disease. However, much of our ability to control embryonic stem cell self-renewal and directed differentiation currently involves genetic manipulation of these cells or complex mixtures of protein factors. The demonstration that one can systematically identify, optimize and characterize the mechanism of action of small drug-like molecules that selectively control stem cell biology both in vitro and in vivo will: (1) provide important tools to manipulate stem cells in the lab; (2) provide new insights into the complex biology that regulates stem cell differentiation; and (3) provide an important first step which may ultimately lead to drugs that facilitate the clinical application of stem cells.
Publications
- Angew Chem Int Ed Engl (2011): Dorsomorphin Promotes Human Embryonic Stem Cell Self-Renewal. (PubMed: 21384475)
- Proc Natl Acad Sci U S A (2010): Screening the mammalian extracellular proteome for regulators of embryonic human stem cell pluripotency. (PubMed: 20133595)
- Cell Stem Cell (2009): A small molecule primes embryonic stem cells for differentiation. (PubMed: 19427291)
