Office: 843-792-0849
Lab: 843-792-0851
Fax: 843-792-8565
Email: hsuy@musc.edu
BSB-512C

Research Interests

Research studies in my laboratory are directed towards understanding the molecular mechanisms of apoptosis, a naturally occurring cell elimination process that plays an important role under both physiological and pathological conditions. Currently, we are using biochemical, molecular biological, cell biological and immunochemical approaches to study how members of the Bcl-2 family regulate cell death. This family of proteins can promote either cell survival as in the case of Bcl-2 and Bcl-X_L or cell death as in the case of Bax and Bak. They are believed to play important roles in tissue development and cancer.  To carry out our studies, we are generating monoclonal antibodies against the Bcl-2 family proteins for biochemical and immunochemical studies. In addition, we are tagging these proteins with green fluorescent proteins to monitor their subcellular distribution in live cells by confocal microscopy. Our studies so far have shown that Bax and Bcl-X_L translocate from the cytosol to mitochondria during apoptosis and the mitochondrial localization of these proteins may be crucial for their apoptosis regulating functions. Currently, we are in the process of identifying the mitocondrial receptors for these proteins as a first step towards our long-term goal of mapping the biochemical pathways underlying apoptosis.

Selected Publications

• Hsu, Y.-T ., Hou, Q., Zhou, H., and Mohanty, S., and Litvinchuk, A. (2005) Differential immunoscreening identifies a glycosylation variant of the epidermal growth factor receptor in ME-180 cervical carcinoma cells. Hybridoma 24, 225-230.
• Zhou, H., Hou, Q., Chai, Y., and Hsu, Y.-T. (2005) Distinct Domains of Bcl-X L are involved in Bax and Bad antagonism and in apoptosis inhibition. Exp. Cell Res. 309, 316-28
• Hou, Q. and Hsu, Y.-T. (2005) Bax translocates from cytosol to mitochondria in cardiac cells during apoptosis: development of a GFP-Bax-stable H9c2 cell line for apoptosis analysis. Am J Physiol Heart Circ Physiol. 289, H477-87.
• Birbes, H., Luberto, C., Hsu, Y.-T., El Bawab, S., Hannun, Y.A., and Obeid, L.M. (2005) A Mitochondrial pool of sphingomyelin is involved in TNF a -induced Bax translocation to mitochondria. Biochem. J. 386, 445-451
• Jeong, S.-Y., Gaume , B., Lee, Y.-J., Hsu, Y.-T., Ryu, S.W., Sharpe, J.C., and Youle, R.J. (2004) Bcl-xL sequesters its C-terminal membrane anchor in soluble, cytosolic homodimers. EMBO23, 2146-2155.
• Hsu, Y.-T , Mohanty, S., Litvinchuk, A., and Hou, Q. (2004) Generation and characterization of monoclonal antibodies directed against the surface antigens of cervical cancer cells. Hybridoma and Hybridomics 23, 121-125.
• Hou, Q., Cymbalyuk, E., Hsu, S.-C., Xu, M., Hsu,Y.-T. (2003) Apoptosis modulatory activities of transiently expressed Bcl-2: Roles in cytochrome c release and Bax regulation. Apoptosis8, 617-629.
• Y.-T. Hsu, Q. Hou, E. Cymbalyuk, and R.J. Youle (2003) Generation and characterization of species-specific anti-Bcl-X L monoclonal antibodies. Hybridoma and Hybridomics 22, 91-95.
• Smaili, S.S., Hsu, Y.-T., Sanders, K.M., Russell, J.T., and Youle, R.J. (2001) Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential. Cell Death Diff. 8(9): 909-920.
• Nechushtan, A., Smith, C. L., Hsu, Y.-T., and Youle, R. J. (1999) Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J. 18: 2330-2341.
• Hsu, Y.-T., and Youle, R. J. (1999) Bax, a death effector molecule: its role in development and oncogenesis. Apop. and Cancer Chemo. 5: 117-128.
• Basañez, G., Nechushtan, A., Drozhinin, O., Chanturiya, A., Choe, E., Tutt, S., Wood, K., Hsu, Y.-T., Zimmerberg, J., and Youle, R. J. (1999) Bax, but not Bcl-X_L, decreases the lifetime of planar phospholipid bilayer membranes at sub-nanomolar concentrations. Proc. Natl. Acad. Sci. 96:5492 - 5497.
• Nechushtan, A., Smith, C. L., Hsu, Y.-T., and Youle, R. J. (1999) Conformation of the Bax C-terminus regulates subcellular location and cell death, EMBO18, 2330-2341.
• Hsu, Y.-T., and Youle, R. J. (1998) Bax in murine thymus is a soluble monomeric protein which displays differential detergent-induced conformations. J. Biol. Chem. 273: 10777-10783.
• Castelli, J.C., Hassel, B. A., Maran, A., Paranjape, J., Hewitt, J. A., Li, X.-L., Hsu, Y.-T., Silverman, R. H., and Youle, R. J. (1998) The role of 2'-5' oligoadenylate-activated ribonuclease L in apoptosis. Cell Death and Diff. 5: 313-320.
• Hsu, Y.-T., Wolter, K. G., and Youle, R.J. (1997) Cytosol-to-membrane redistribution of Bax and Bcl-X_L during apoptosis. Proc. Natl. Acad. Sci. 94: 3668-3672.
• Hsu, Y.-T., and Youle, R.J. (1997) Nonionic detergents induce dimerization among members of the Bcl-2 family. J. Biol. Chem. 272: 13829-13834.
• Wolter, K. G., Hsu, Y.-T., Smith, C. L., Nechushtan, A., Xi, X.-G. and Youle, R. J. (1997) Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol. 139: 1281-1292.
• Hsu, Y.-T., Wolter, K. G., and Youle, R. J. (1997) Cytosol-to-membrane redistribution of Bax and Bcl-X L during apoptosis, Proc. Natl. Acad. Sci.94, 3668-3672.
• Chen, T.-Y., Illing, M., Molday, L. L., Hsu, Y.-T., Yau, K. W., and Molday, R. S. (1994) Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca 2+-calmodulin modulation, Proc. Natl. Acad. Sci. 91, 11757-61
• Hsu, Y.-T. and Molday, R. S. (1994) Interaction of calmodulin with the cyclic cGMP-gated channel of rod photoreceptor cells. Modulation of activity, affinity purification, and localization, J. Biol. Chem. 269, 29765-70.
• Hsu, Y.-T ., Wong, S. Y. C., Connell, G. J., and Molday, R. S. (1993) Structural and functional properties of rhodopsin from rod outer segment disk and plasma membrane, Biochim. et Biophys. Acta1145, 85-92.
• Hsu, Y.-T. and Molday, R. S. (1993) Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin, Nature361, 76-79.