Regulation of Adult Stem Cell Proliferation and Number

Funding Type: 
New Faculty I
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Our research focuses on developing new tools and models for the next generation of doctors and scientists in all specialties of regenerative medicine. The major obstacles in regenerative medicine are the limited number of pre-existing stem cells and the lack of human models to study organ repair. Our first aim is to identify the mechanisms that regulate adult stem cell proliferation. We propose to use this knowledge to produce cell-permeable proteins to reactivate proliferation in dormant stem cells. Our second aim is to identify how the adult stem cell fate is specified. This knowledge will be used to increase the number of pre-existing stem cells in an organ. Our third aim is to develop a model of human organ development, where we can test the approaches of promoting organ-stem cell populations to form, activating stem cell populations to divide, and activating signaling centers to sustain patterned growth.

As a model to study adult stem cell quiescence and activation, we use the stem cells of the hair follicle to identify proteins that regulate cell cycle. We think that regulate the cell cycle of the hair stem cells will also function in other adult stem cells. The products of this research will be cell-permeable proteins that mimic the activation of hair stem cells and could be applied to other organ systems to induce regeneration. As a model to study stem cell identity, we are using both embryonic and adult models to determine whether the signals that induce embryonic stem cell identity are the same as in the adult. Our third model is to study epidermal organ-like structures produced by human ES cells. By developing reporters for early development of epidermal organs, we will be able to study how stem cell compartments form during human organ development. We hope that the wide community of scientists at UCSD will benefit from our epidermal organ studies so that these advances can be applied to other organ-specific stem cell compartments.

Statement of Benefit to California: 

A major goal of regenerative medicine is to replace organs and tissues lost from disease or injury using our own body’s cells. Our research focuses on approaches to induce pre-existing stem cells to divide and to develop models of human organ development to study regeneration. This research will greatly benefit the next generation of regenerative doctors and scientists and benefit the California economy now through the development of new tools and jobs.

The major obstacles in regenerative medicine are the limited number of pre-existing stem cells and the lack of human models to study organ repair. Our aims are to identify the mechanisms that regulate stem cell proliferation and that induce stem cell formation, using the hair follicle as a model. The hair follicle regenerated itself 10-20 times during a lifetime and its stem cells are readily accessible. We hope to translate our findings in the hair follicle into developing cell-permeable proteins to induce stem cells in other organs to divide. The products of this research will aid California by helping to speed recovery and to provide therapies for diseases once thought to cause permanent damage. These tools could reduce the suffering and long-term health consequences following organ damage, which should benefit all Californians. We also propose to generate a human model of organ development that should provide the next generation of California scientists and doctors with the lead in developing innovative treatments of diseases in all organ types. This approach should also benefit the health, biotechnology, and pharmaceutical industries of California.