Molecular & Cellular Biology

2014 Recipient

Ming-Jer Tsai, Ph.D.

Drs. Tsai and Tsai have played an essential role in creating a new field on nuclear orphan receptors. Their nomination for this award was based on major contributions to the role of COUP-TFII. They showed that COUP-TFII is overexpressed in metastatic prostate cancer and its expression is an excellent prognostic marker for aggressive prostate cancer. They further showed that COUP-TFII could break down the barrier inducted by indolent prostate cancer and promote the progression of cancer into an aggressive state. In another study, they found that COUP-TFII controls ~50 percent of the expression of all atrium and ventricle specific genes, which suggests that COUP-TFII is the major regulator determining the specification of atrium vs ventricle during heart development. Finally, they showed that COUP-TFII directly regulated the expression of both Eya1 and Wt1 in the metanephric mesenchyme. Their findings show that COUP-TFII plays a central role in the specification of metanephric fate and in the maintenance of metanephric mesenchyme proliferation and survival by acting as a crucial regulator of Eya1 and Wt1 expression.

Drs. Tsai and Tsai’s nomination was based on the following publications: 

 Qin JWu SPCreighton CJDai FXie XCheng CMFrolov AAyala GLin XFeng XHIttmann MMTsai SJTsai MJTsai SYCOUP-TFII inhibits TGF-β-induced growth barrier to promote prostate tumorigenesisNature. 2013 Jan 10; 493(7431):236-40.

Wu SPCheng CMLanz RBWang TRespress JLAther SChen WTsai SJWehrens XHTsai MJTsai SY.  Atrial identity is determined by a COUP-TFII regulatory network Dev Cell. 2013 May 28; 25(4):417-26.

Yu CT1, Tang KSuh JMJiang RTsai SYTsai MJ. COUP-TFII is essential for metanephric mesenchyme formation and kidney precursor cell survival. Development. 2012 Jul;139(13):2330-9.

2002 Recipient

Nuclear orphan receptor COUP-TFII and organogenesis

Ming-Jer Tsai, Ph.D. and Sophia Y. Tsai, Ph.D., both received the award for their research in dissecting the in vivo function of nuclear orphan receptors, COUP-TFI and COUP-TFII. COUP-TFs have been shown to play important roles in development. COUP-TFI null mice exhibit defects in axon guidance, in cortical layer formation, in brain regionalization, and axon myelination. These results indicate that COUP-TFI is critical for the function of the central and peripheral nervous system. COUP-TFII null mice display defects in angiogenesis and heart development and die before E 10.0. Tissue specific knock out of COUP-TFII in the stomach shows posterior transformation and aberrant muscle differentiation. Both phenotypes implicate COUP-TFII as a mediator of the hedgehog signaling pathway. In addition, haploid insufficiency is shown in COUP-TFII heterozygous mutants. The expression patterns and the phenotypes exhibited by the COUP-TFII mutants suggest that COUP-TFII is essential for organogenesis in tissues requiring mesenchymal-epithelial interactions. Taken together, the above findings indicate that COUP-TFI and COUP-TFII serve vital functions during development and raise the possibility of future ligand based therapy for disease treatment.

Dr. Tsai and Tsai’s research was based on the following publications:

Pereira FA, Qiu Y, Zhou G, Tsai MJ, Tsai SY. The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes Dev. 1999 Apr 15;13(8):1037-49.

Zhou C, Qiu Y, Pereira FA, Crair MC, Tsai SY, Tsai MJ. The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons. Neuron. 1999 Dec;24(4):847-59.

Huang HP, Liu M, El-Hodiri HM, Chu K, Jamrich M, Tsai MJ. Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Mol Cell Biol. 2000 May;20(9):3292-307. 

Zhou C, Tsai SY, Tsai MJ. COUP-TFI: an intrinsic factor for early regionalization of the neocortex.Genes Dev. 2001 Aug 15;15(16):2054-9.