New Faculty Award Supplement

New Faculty Award Supplement

Funding Type: 
New Faculty II
Grant Number: 
RN2-00908
Award Value: 
$3,017,978
Stem Cell Use: 
Embryonic Stem Cell
Status: 
Active
Public Abstract: 
Statement of Benefit to California: 
Progress Report: 

Year 1

Our research proposal focuses on understanding the global regulation of adult stem cells, both in the setting of normal growth and in disease. Under certain conditions, adult stem cells become refractory to stimulation and growth. The mechanisms of this refractory growth are unknown but may contribute to the inadequate regeneration. As a model to study mechanisms of adult stem cell growth and disease, we are studying the hair follicle, which regenerates itself several times during our lifetime. A rare disease in humans causes the hair cycle to stop so that no new hair is regenerated. We have uncovered two molecular pathways that are defective in this disease that might explain the inability of the hair to regenerate. In addition, we have made progress in developing cell-based models to study the regulatory pathways that normally control these molecular pathways. This latter model will be used to perform drug-based screens to identify compounds that can interact with these pathways and could be used to treat refractory stem cell diseases.

Year 2

The overall goals of our investigations are to better understand the links between stem cell proliferation, differentiation, and ultimately regeneration. Using the hair follicle and embryonic stem cells, the regulation of organ-specific and non-organ-specific stem cells can be studied. In the past year, we have published our working, characterizing a model of hair stem cell defects. This model has been the basis for our ongoing studies to identify mechanisms to mobilize refractory stem cells. In addition, we have identified different mechanisms for how stem cells potentially forecast growth by preparing proteins and RNAs that they require before they differentiate. Future work in this area is necessary to attempt to stimulate organ regeneration in tissues that are refractory for self-healing.

Year 3

The primary goals of our CIRM-funded research are to investigate the mechanisms of stem cell proliferation and refractoriness in adult and embryonic stem cells. Our focus has been on pathways that are functionally important to stem cell proliferation that are targetable by small molecules or by approaches that are unlikely to cause DNA damage. The outcome of such research may be the identification of targetable pathways in activating or suppressing stem cell proliferation during organ regeneration.

Year 4

The primary goals of our CIRM-funded research are to investigate the mechanisms of stem cell proliferation and refractoriness in adult and embryonic stem cells. Our focus has been on pathways that are functionally important to stem cell proliferation that are targetable by small molecules or by approaches that are unlikely to cause DNA damage. The outcome of such research may be the identification of targetable pathways in activating or suppressing stem cell proliferation during organ regeneration.

Year 5

Tissue regeneration requires the activation and mobilization of specialized cells called stem cells. These cells are responsible for producing new cells to replace a tissue or organ during injury. In many tissues, these cells stay dormant until they are stimulated to grow. These stem cells are important not only for their role in tissue regeneration but in many diseases are the point of origin for cancer. Thus understanding what regulates the growth of stem cells is important for many areas of human health. The signals that stimulate stem cell growth are not well known. My lab studies how progenitors grow using the hair follicle and embryonic stem cells as models of tissue and organ development. With funding from the California Institute of Regenerative Medicine, our lab has developed new methods and discovered new properties for stem cell growth. First, we discovered that abnormalities outside of the stem cell compartment can interfere with stem cell growth (Mukhopadhyay 2011). Second, we discovered about different levels of the same signal can control an important growth factor called Sonic Hedgehog in hair follicle growth (Mukhopadhyay 2012). Third, we are learning about how basic units of a stem cell are regulated during their growth. These units, called ribosomes and histones, regulate the synthesis of new proteins or control genes, respectively, and have unique characteristics in stem cells. By studying these areas, we hope to understand unique targets to regulate stem cell growth.

Year 6

Tissue regeneration requires the activation and mobilization of specialized cells called stem cells. These cells are responsible for producing new cells to replace a tissue or organ during injury. In many tissues, these cells stay dormant until they are stimulated to grow. These stem cells are important not only for their role in tissue regeneration but in many diseases are the point of origin for cancer. Thus understanding what regulates the growth of stem cells is important for many areas of human health. The signals that stimulate stem cell growth and maintain their identity are not well known. To answer these questions, my lab investigates how progenitors grow and how progenitors are maintained using two models of stem cells, the skin and embryonic stem cells. Funding from the California Institute of Regenerative Medicine has allowed my lab to develop new tools to study the properties of stem cell growth. Using these tools, we discovered that how signals outside of the stem cell compartment interfere with stem cell growth (Mukhopadhyay 2011) and downstream signals (Mukhopadhyay 2012). We also found new differences between stem cells of different genders including their response to pharmacologic treatments. Lastly, we are learning about how basic units of a stem cell are regulated during their growth. These units, called ribosomes and histones, regulate the synthesis of new proteins or control genes, respectively, and have unique characteristics in stem cells. By studying these areas, we hope to understand unique targets to regulate stem cell growth.

© 2013 California Institute for Regenerative Medicine