Professor, Baylor College of Medicine
Charles C. Bell Research Professor
B.S., National Taiwan University, 1966
Ph.D., University of California, Davis, 1971
Postdoc, The University of Texas, M.D. Anderson Cancer Center, Houston, 1971-73
Role of transcription factors in development and diseases
We are interested in understanding the role of transcription factors in gene regulation, development and diseases. Our research has been concentrated in the following three areas:
1. BETA2/NeuroD in pancreatic islet and neuronal development
The insulin gene is regulated in a tissue and developmental-specific manner. In our laboratory, we have isolated a tissue-specific transcription factor BETA2 that can regulate its transcription. Its role in insulin gene activity and islet cell fate determination are carried out by gene knockout experiment. Results indicate that BETA2 is essential for proper morphogenesis of pancreatic islets and cell fate determination of several enteroendocrine cells. In addition, we also found that the proper differentiation of several neuronal cell types such as granule cells of the hippocampus and cerebellum, photoreceptor cells of retina, as well as the ganglions of the number VIII nerve are compromised. These defects result in behavior abnormalities such as epilepsy, hyperactivity, imbalance and deafness. Currently, we are analyzing the target genes that are responsible for these defects and modifying mechanism of these defects. In addition, using Ngn3, a bHLH transcription factor, as a marker and molecular genetic approaches to mark Ngn3 cells, we have isolated islet progenitor/stem cells. These cells will be characterized for future treatment of diabetes using in vitro produced islets from these progenitor/stem cells.
2. Molecular developmental biology of COUP-Transcription factors
COUP-TFs are orphan members of the steroid/thyroid receptor superfamily. Using a molecular approach in collaboration with Dr. Sophia Tsai’s laboratory, we have found that COUP-TFs are silencers and able to negatively regulate other receptors such as RAR, RXR, TR, VDR and PPAR activities. These results suggest that they play an important role in cellular development and differentiation. We are using cellular, molecular and genetic approaches to determine the precise role(s) of these transcription factors in mouse development. Results indicated that COUP-TFI is important in neurodevelopment, axonal guidance, brain regionalization and bone morphogenesis and COUP-TFII is important for angiogenesis, heart development, adipogenesis and organogenesis. Currently, we are trying to dissect the underlying mechanism of these defects.
3. Role of nuclear receptor coactivators and corepressors in prostate cancer
It has been shown that androgen and its receptor play an important role in the formation and progression of prostate tumor. Activation of target genes by androgen receptor, however, requires the participation of coactivators and corepressors. Many cofactors have been identified to interact with and activate androgen receptor activity. In our laboratory, we are interesting in determining whether any of these cofactors has a role in prostate tumors. Using in situ hybridization, we have identified SRC-3 to be over-expressed in 47% of prostate tumor samples. Our goal is to dissect the role of SRC-3 in cell growth and formation of prostate tumor using transgenic mice as a model.
Yan J, Erdem H, Li R, Cai Y, Ayala G, Ittmann M, Yu-Lee LY, Tsai SY, Tsai MJ (2008) Steroid receptor coactivator-3/AIB1 promotes cell migration and invasiveness through focal adhesion turnover and matrix metalloproteinase expression. Cancer Research 68:5460-5468.
Li L, Xie X, Qin J, Jeha GS, Saha PK, Yan J, Haueter CM, Chan L, Tsai SY, Tsai MJ (2009) The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism. Cell Metabolism 9:77-87.
Kim BJ, Takamoto N, Yan J, Tsai SY, Tsai MJ (2009) Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) regulates growth and patterning of the postnatal mouse cerebellum. Developmental Biology 326:378-391.
Tang K, Xie X, Park JI, Jamrich M, Tsai S, Tsai MJ (2010) COUP-TFs regulate eye development by controlling factors essential for optic vesicle morphogenesis. Development 137:725-734.
Wu SP, Lee DK, Demayo FJ, Tsai SY, Tsai MJ (2010) Generation of ES cells for conditional expression of nuclear receptors and coregulators in vivo. Molecular Endocrinology 24:1297-1304.
Xie X, Qin J, Lin SH, Tsai SY, Tsai MJ (2011) Nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) modulates mesenchymal cell commitment and differentiation. Proceedings of the National Academy of Sciences USA 108:14843-14848.
Tang K, Rubenstein JL, Tsai SY, Tsai MJ (2012) COUP-TFII controls amygdala patterning by regulating neuropilin expression. Development 139:1630-1639.
Yu CT, Tang K, Suh JM, Jiang R, Tsai SY, Tsai MJ (2012) COUP-TFII is essential for metanephric mesenchyme formation and kidney precursor cell survival. Development 139:2330-2339.
Ming-Jer Tsai, Ph.D.
Department of Molecular and Cellular Biology
Baylor College of Medicine
One Baylor Plaza M734
Houston, Texas 77030, U.S.A.
Tel: (713) 798-6253
Fax: (713) 798-8227