Hoang Nguyen, Ph.D.
Departments of Molecular and Cellular Biology and Dermatology,
Center for Stem Cell and Regenerative Medicine,
Center for Cell and Gene Therapy
Ph.D.: Cornell Medical College/Sloan-Kettering Institute, New York
Postdoctoral training: Rockefeller University, New York
Transcriptional Regulation of Skin Epithelial Stem Cell Fate
Our lab’s main interest is to understand the molecular mechanisms of self-renewal and differentiation of stem cells. We use the mammalian skin as a model system to study stem cells, because skin is a self-renewing tissue whose large pool of stem cells are regularly activated throughout the animal’s lifespan.
Wnt signaling pathway plays an important role in many developmental processes, including self-renewing and differentiation of stem cells. Depending on the cofactors that are present, the transcription factors Tcf3 and Tcf4 can either repress or activate Wnt-responsive genes. Previously, we found that both Tcf3 and Tcf4 are expressed in embryonic and adult epidermal stem cells, and that they play a crucial role in maintaining the self-renewal capacity of stem cells.
We are currently pursuing the following questions: 1) What are the target genes of Tcf3/4 that are responsible for maintaining the undifferentiated state of stem cells and how do these genes exert that function? 2) What are the regulatory factors that turn on Tcf3/4 expression in skin stem cells, and conversely what repressive factors turn them off in committed cells? 3) How are these genes altered during the aging process and how they are dysregulated in different diseases?
Answering these questions will provide a deeper understanding of how stem cells maintain their multipotent status and control cell fate specification. Since cancer cells often display many characteristics of stem cells, studying the molecular mechanisms of how stem cells maintain their multipotent undifferentiated state is important for regenerative medicine as well as for the development of anti-cancer therapeutics.
Baylor College of Medicine
One Baylor Plaza, Alkek N1120
Houston, TX 77030
- Nguyen H, Merrill B, Polak L, Nikolova M, Rendl M, Shaver TM, Pasolli HA, and Fuchs E. (2009). Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia. Nature Genetics 41(10): 1068-75.
- Nguyen H, Rendl M and Fuchs E. (2006). Tcf3 governs stem cell features and represses cell fate determination in skin. Cell 127:171-183.
- Liu Y, Hedvat DV, Mao S, Zhu XH, Yao J, Nguyen H, Koff A and Nimer SD. (2006). The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2. MCB 8:3114-3123.
- Xhu X, Nguyen H, Halicka H, Traganos F and Koff A. (2004). Noncatalytic requirement for CyclinA-cdk2 in p27 turn over. 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 proteassome. MCB 19:1190-1201.
- Millard SS, Yan JS, 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.
- Gudas JM, Nguyen H, Li T, Katayose D, Seth P and Cowan KH. (1995). Effects of cell cycle, DNA damage and wild-type p53 on p21Cip1 expression in human mammary epithelial cells. Oncogene 11:253-261.
- Gudas JM, Nguyen H, Klein RC, Katayose D, Seth P and Cowan KH. (1995). Differential expression of multiple MDM2 messenger RNAs and proteins in normal and tumorigenic breast epithelial cells. Clinical Cancer Res 1:71-80.
- Gudas JM, Nguyen H and Cowan KH. (1995). Hormone-dependent regulation of BRCA1 in human breast cancer cells. Cancer Res. 55:4561-4565.