CHIH-CHENG TSAI, Ph.D.

RESEARCH:

Transcriptional cofactors, nuclear receptors, Notch, EGFR, Drosophila development, SCA1, DRPLA, neurodeneration

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(1) Atrophin family proteins; (2) Ataxin-1 family proteins; and (3) SMRT family proteins are three different classes of conserved transcriptional cofactors. My lab studies their transcriptional properties and investigates their involvement in the pathways of nuclear receptors, Notch, and EGFR (epidermal growth factor receptor) in connection with Drosophila development and human diseases. Glutamine-repeat expansion in Atrophin-1 and in Ataxin-1 causes the neurodegenerative dentatorubral-pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 1(SCA1), respectively. So far, however, the mechanisms by which mutant Atrophin-1 or mutant Ataxin-1 causes neurodegeneration remain elusive. One focus of our investigations is to determine whether disruption in the nuclear receptor, Notch, or EGFR signaling pathways contributes to the development of DRPLA and SCA1. Because these transcriptional cofactors and the signaling pathways that they take part in are conserved in both vertebrates and invertebrates, my lab uses a combination of Drosophila, mouse, and cultured human cells for our research.

PUBLICATIONS:

Heck, B.W., Zhang, B., Tong, X., Pan, Z., Deng, W.-M., Tsai, C.-C. The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila Development. Biology Open (2011). Accepted.

Tong, X., Gui, H., Jin, F., Heck, B. H., Lin, P., Ma, J., Fondell, J. D., and Tsai, C.-C. Ataxin-1 and Brother of Ataxin-1 are components of the Notch signaling pathway. EMBO Reports 12 (5), 428-435 (2011).

Gui, H., Li, M.-L., Tsai, C.-C. A tale of Tailless. Developmental Neuroscience, 33 (1): 1-13 (2011).

Escher, P, Gouras P, Roduit, R, Tiab, L, Bolay, S, Delarive, T, Chen, S, Tsai, C-C, Hayashi M, Zernant, J, Merriam, JE, Mermod, N, Allikmets, R, Munier, FL, Schorderet, DF. Mutations in NR2E3 can cause dominant or recessive retinal degenerations in the same family. Human Mutation 30(3):342-51 (2009).

Wang, L. and Tsai, C.-C. Atrophin proteins: An overview of a new class of nuclear receptor co-repressors. Nuclear Receptor Signaling, 6, e009 (2008). Review article.

Wang, L., Charroux, B., Kerridge, S., Tsai, C.-C. Atrophin recruits HDAC1/2 and G9a to modify histone H3-lysine 9 and to determine cell fates. EMBO Reports 9, 6, 555-62 (2008). Cover Article.

Bolger, T.A., Zhao, X., Cohen, T.J., Tsai, C.-C. , Yao , T.P. Neurodegenerative disease protein ataxin-1 antagonizes the neuronal survival function of MEF2. J Bio Chem 282, 29186-92 (2007).

Wang, L., Rajan, H., Pitman, J.L., McKeown, M.M., Tsai, C.-C. Histone deacetylase-associating Atrophin proteins are nuclear receptor co-repressors. Genes & Development 20, 525-530 (2006). Featured on cover.

Mizutani, A., Wang, L., Rajan, H., Vig, PJS, Alaynick , WA , Thaler, JP, Tsai, C.-C. Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1. EMBO Journal 24, 3339-51 (2005).

Tsai, C.-C. and Fondell, J. Nuclear receptor recruitment of histone-modifying enzymes to target gene promoters. Vitam Horm . 93-122 (2004). Review article.

Tsai, C.-C. , Kao, H.-Y., Mizutani, A., Banayo, E., Rajan. H., McKeown M., and Evans, R. M. Ataxin-1, a SCA1 neurodegenerative disorder protein, is functionally linked to the transcriptional co-repressor of retinoid and thyroid hormone receptors. Proc Natl Acad Sci USA 101, 4047-4052 (2004). Faculty of 1000 article.

Donaldson KM, Li W, Ching KA, Batalov S, Tsai C.-C. , Joazeiro CA. Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates. Proc Natl Acad Sci USA 100, 8892-8897 (2003).

Pitman, J. L., Tsai, C.-C. , Edeen, P. T., Finley, K. D., Evans, R. M., McKeown, M. Multiple mechanisms modify the repressive activity of the DSF nuclear receptor. Developmental Biology 245, 315-328 (2002).

Kao, H.-Y., Verdel, A, Tsai, C.-C. , Simon, C, Juguilon, H, Khochbin, S. Mechanism for nucleocytoplasmic shuttling of HDAC7. J Bio Chem 277, 187-193 (2002).

Tsai, C.-C. *, Ghbeish, N.*, Schubiger, M., Zhou, J. Y., Evans, R.M., and McKeown, M. The dual role of Ultraspiracle, the Drosophila RXR, in ecdysone response. Proc Natl Acad Sci USA 98, 3967-3872 (2001). ( * Co-first authors ) .

Shi, Y., Downes, M., Xie, W., Kao, H.-Y., Ordentlich, P., Tsai, C.-C. , Hon, M., Evans, R. M. SHARP, an inducible cofactor that integrates nuclear receptor repression and activation. Genes & Development 15, 1140-1151 (2001) .

Tsai, C.-C. , Kao, H.-Y., Yao , T.-P., McKeown, M., Evans, R. M. SMRTER, a Drosophila nuclear receptor co-regulator, reveals that EcR-mediated repression is critical for development. Molecular Cell 4, 175-186 (1999). Cover Article.

Rutgers/UMDNJ GRADUATE PROGRAM AFFILLIATION:

• Biochemistry
• Neuroscience
• Cell and Developmental Biology
• Physiology and Integrative Biology