Cellular and Developmental Biology, State University of New York at Stony Brook, (1994)
|Fellowship/Advanced Training: |
Postdoctoral fellowship in Cutaneous Biology and Gene Transfer (1995-1999)
Gene/cell-based regenerative therapies; epithelial stem cell research; Regulation of cell plasticity during repair and regeneration.The goal of regenerative medicine is to use gene- and cell-based therapies to restore tissue function. In many adult tissues, tissue homeostasis and regeneration are maintained by resident stem cells that have the ability to self-renew and to generate differentiated cell lineages. My lab has been investigating the organization and behavior of stem cells in normal and regenerative epithelial tissues using skin epithelia and salivary glands as model systems for rapidly and slowly renewing tissues, respectively. Our long-term goal is to gain insights into the cellular and molecular mechanisms regulating tissue repair and regeneration in epithelial tissues.
Our studies are currently focusing on two projects:
1) Using skin epithelia, we have discovered that differentiated keratinocytes possess inducible plasticity and acquire stem cell characteristics during tissue damage/regeneration. We have identified a key role for protein kinase D in regulating dedifferentiation, cutaneous wound healing and tumorigenesis. Our ongoing studies are focused on characterization of common and unique roles of PKD isozymes in human skin and the cross-talks with other signaling pathways that regulate epidermal homeostasis, survival, migration and tumorigenesis.
2) Contrary to epidermis, salivary gland is a slowly renewing tissue with a limited regenerative capacity. Recent lineage tracing studies have shown that ductal cell lineages in salivary glands are maintained by lineage-restricted stem cells while acini are maintained by self-duplication of acinar cells. Following severe injury, however, ductal cells transdifferentiate to acinar cells and contribute to regeneration of acini. We are using techniques including cell-lineage tracing and transcriptome analysis to delineate the mechanism of injury-induced cell plasticity in salivary glands and to identify signaling pathways important in this process. These studies will inform approaches for modulating the pathways that may promote endogenous regeneration as well as the generation of exogenous salivary gland cell lineages from pluripotent stem cells.