The Cellular and Molecular Identity of the Stem Cell Niche
Feedback regulation by stem cell progeny We have pioneered studies to identify stem cell progeny as important regulators of activity of parental stem cells (Hsu et al., Cell 2011, Hsu et al., Cell 2014). Currently, we are identifying specific signaling factors that govern this feedback regulation.
Identification of novel niche cell types and signals With new tools that we established, we are systematically identifying novel cell types and secreted factors that govern stem cell quiescence, promote stem cell self-renewal, and instruct stem cell fate decisions.
Modification of stem cell behavior to enhance wound repair More than 100 million people develop scars each year as a result of trauma, surgery, or burns. At least 6 million people suffer from chronic non-healing wounds (including diabetic foot ulcers and bedsores). We are applying what we have learned about how the niche regulates skin stem cells to develop novel wound healing strategies.
Function and Biology of Transit-Amplifying Cells
TACs of one tissue control changes in many neighboring tissues How tissues of different lineage grow together in an organ is a fundamental question in developmental biology. We discovered that hair follicle TACs control growth of the hair follicle itself and production of neighboring dermal adipocytes, coupling activity of two lineages (Zhang et al, G&D 2016). Currently, we are defining TAC function in regulating other tissues in the skin.
TACs and chemotherapy-related side effects The highly proliferative nature of TACs is what makes them, not slow-cycling stem cells, a primary target of cytotoxic chemotherapies. Thus, understanding TAC function may inform strategies to prevent chemotherapy-related damage to tissues and organs. By studying the biology of TACs, we have discovered the root causes for several chemotherapy-related side effects, including hair loss, delayed wound healing, and susceptibility to infections. We are working on the cellular and molecular mechanisms leading to these phenotypes.