Professor, Baylor College of Medicine
B.S., University of Wisconsin, Madison, 1964
M.S., University of Wisconsin, Madison, 1965
Ph.D., University of California, Davis, 1969
Postdoc, Cornell University, Ithaca, NY, 1970-71
Physiological role of nuclear receptors during development
Our research focuses on two main areas: the first is to examine the physiological role of nuclear orphan receptor COUP-TFII in mouse development. COUP-TFs are members of the nuclear receptor superfamily. We have previously demonstrated that COUP-TFs, I and II, function as negative or positive regulators to regulate their target gene expression. COUP-TFI is highly expressed in the CNS and PNS, and COUP-TFII is highly expressed in the mesenchyme of the developing organs. Although the expression of COUP-TFI and II overlaps, ablation of either COUP-TF I or II in mice results in lethality, indicating that each has its distinct function and both are vital for animal survival. COUP-TFI null mutants exhibit defects in axon guidance, myelination, forebrain regionalization, bone and inner ear morphogenesis while COUP-TFII null mutants exhibit defects in angiogenesis and heart development. Currently, we concentrate our effort in studying the underlying mechanism by which COUP-TFII regulates angiogenesis and heart development using floxed COUP-TFII mice. We are also examining its role in the development and function of stomach, liver, limb and brain by crossing them to various Cre mice to generate tissue specific COUP-TFII null mice. Finally, we use chimera analysis and demonstrate that COUP-TFII plays cell autonomous function in limb outgrowth and umbilical vessel development.
The second area of our research is to study the interaction of oncogenes and hormones in mammary gland tumorigenesis. We generated a ligand inducible system to express oncogenes in mammary gland and demonstrated ectopic inducible expression of int-2 in mammary gland results in mammary gland hyperplasia. The induced hyperplasia is reversible, and the extent of hyperplasia depends on the levels and the length of expression of int-2. Currently, we are using three transgenic models, to induce expression of either int-2, AIB-1 or Cdc25B, to investigate the interaction of oncogenes and hormones in the transformation of the mammary gland epithelium.
Suh JM, Yu CT, Tang K, Tanaka T, Kodama T, Tsai MJ, Tsai SY (2006) The expression profiles of nuclear receptors in the developing and adult kidney. Molecular Endocrinology 20:3412-3420.
Qin J, Suh JM, Kim BJ, Yu CT, Tanaka T, Kodama T, Tsai MJ, Tsai SY (2007) The expression pattern of nuclear receptors during cerebellar development. Developmental Dynamics 236:810-820.
Petit FG, Jamin SP, Kurihara I, Behringer RR, DeMayo FJ, Tsai MJ, Tsai SY (2007) Deletion of the orphan nuclear receptor COUP-TFII in uterus leads to placental deficiency. Proceedings of the National Academy of Sciences USA 104:6293-6298.
Kurihara I, Lee DK, Petit FG, Jeong J, Lee K, Lydon JP, DeMayo FJ, Tsai MJ, Tsai SY (2007) COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity. PLoS Genetics 3:e102.
Qin J, Chen X, Yu-Lee LY, Tsai MJ, Tsai SY (2010) Nuclear receptor COUP-TFII controls pancreatic islet tumor angiogenesis by regulating vascular endothelial growth factor/vascular endothelial growth factor receptor-2 signaling. Cancer Research 70:8812-8821.
Lee DK, Kurihara I, Jeong JW, Lydon JP, DeMayo FJ, Tsai MJ, Tsai SY (2010) Suppression of ERalpha activity by COUP-TFII is essential for successful implantation and decidualization. Molecular Endocrinology 24:930-940.
Lin FJ, Chen X, Qin J, Hong YK, Tsai MJ, Tsai SY (2010) Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development. Journal of Clinical Investigation 120:1694-1707.
Qin J, Chen X, Xie X, Tsai MJ, Tsai SY (2010) COUP-TFII regulates tumor growth and metastasis by modulating tumor angiogenesis. Proceedings of the National Academy of Sciences USA 107:3687-3692.
Chen X, Qin J, Cheng CM, Tsai MJ, Tsai SY (2012) COUP-TFII is a major regulator of cell cycle and Notch signaling pathways. Molecular Endocrinology 26:1268-1277.
Sophia Y. Tsai, Ph.D.
Department of Molecular and Cellular Biology
Baylor College of Medicine
One Baylor Plaza M707
Houston, Texas 77030, U.S.A.
Tel: (713) 798-6251
Fax: (713) 798-8227