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Hoang Nguyen, Ph.D.
| Assistant Professor |
Contact Information:
hoangn@bcm.edu
Office: 713-798-1236
Lab: 713-798-1258
Education:
B.A., Cornell University, Ithaca, NY
Ph.D., Cornell Medical College/ Sloan-Kettering Institute, New York, NY
Postdoctoral fellow, Rockefeller University, New York, NYResearch Interests:
Our main interest is to understand the regulatory network of genes that is required to maintain the stem cell status of stem cells, and the molecular switches that allow cell fate specification. The mammalian skin serves as an amenable model system to study stem cells, because skin is a self-renewing tissue, whose stem cells are maintained and regularly activated throughout the animal’s lifespan. Early embryonic skin epithelium consists of a single layer of unspecified progenitor cells. As development proceeds, some stem cells from the basal layer will differentiate upward to form the stratified epidermis. Some basal cells will communicate with the underlying mesenchyme and move downward to form hair follicles including the sebaceous gland. Through out life, adult stem cells are maintained and are regularly activated to give rise to progenies that further differentiate to maintain skin homeostasis.
We use inducible transgenic and conditional knockout in mice as a model system to dissect the genes that participate in maintaining the multipotent status of stem cells and cell fate specification. Wnt signaling plays an important role in stem cell activation as well as cell fate determination in many systems. The transcription factors Tcf3 and Tcf4, which bind to b-catenin as well as Groucho and CtBP corepressors, are expressed in the single layer epithelium at the embryonic stage when all cells are multipotent. As cell fates are specified, the expression of Tcf3/4 wane and eventually remains confined to the stem cell reservoir of the bulge and its immediate progeny in the outer root sheath (ORS).
Our previous work shows that inducing the expression of Tcf3 in skin cells where Tcf3 is already downregulated prevents the cells from developing into a stratified epidermis, sebaceous gland, and hair. Furthermore, Tcf3 induces an immediate change in genes expression in a pattern similarly found in embryonic and adult skin stem cells. This finding suggests that Tcf3 could revert the cells to an undifferentiated progenitor state and that Tcf3 is required to be downregulated for the cells to differentiate into different lineages.
The immediate major questions to be addressed in the lab are: 1) What are the target genes of Tcf3 that are responsible for maintaining the cells in the undifferentiated state and how do they exert that function? 2) What is the regulatory network that activates Tcf3 and Tcf4 expression in skin progenitor cells and silences its expression in committed cells? Answering these questions will provide a deeper understanding of how stem cells maintain their multipotent status and control cell fate specification. We are also interested in how these networks of genes are regulated and function and in aged stem cells as compared to young stem cells.
Cancer cells often manifest defects of differentiation and display many characteristics of stem cells. Hence studying the molecular mechanisms of how stem cells maintain their multipotent undifferentiated state will be important in the future for both regenerative medicine and anti-cancer therapeutics.Selected Publications
Nguyen, H., Rendl, M., Fuchs, E. (2006). Tcf3 governs stem cell features and represses cell fate determination in skin. Cell 127, 171-183.
Liu, Y., Hedvat, C.V., Mao, S., Zhu, X.H., Yao, J., Nguyen, H., Koff, A., Nimer, S.D. (2006). The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2. MCB 8, 3114-3123.
Zhu, X., Nguyen, H., Halicka H., Traganos, F., and Koff, A. (2004). Noncatalytic requirement for CyclinA-cdk2 in p27 turnover. MCB 13, 6058-6066.
Nguyen, H., Gitig, D., and Koff, A. (1999). Cell free degradation of p27kip1, a G1 cyclin-dependent kinase inhibitor, is dependent on CDK2 activity and the proteasome. MCB 19, 1190-1201.
Millard S.S., Yan, J.S., Nguyen, H., Pagano, M., Kiyokawa, H., and Koff, A. (1997). Enhanced ribosomal association of p27Kip1 mRNA is a mechanism contributing to accumulation during growth arrest. JBC 272: 7093-7098.
©2002,
Cell And Gene Therapy, Baylor College
of Medicine
One Baylor Plaza, N1002, Houston, TX 77030, (713)798-1246
URL: http://www.bcm.edu/genetherapy
Email:cagt@bcm.edu
(Modified:August 15, 2006- SM)
