Department of biochemistry and Molecular biology
Yi-Te Hsu, PhD
1994 Ph.D. (Biochemistry), University of British Columbia, Vancouver, B.C., Canada
1989 B.S. (Biochemistry), University of British Columbia, Vancouver, B.C., Canada
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-XL 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-XL 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.
Hou Q, Jin J, Zhou H, Novgorodov S, Bielawka A, Szulc ZM, Hannun YA, Obeid LM, and Hsu Y-T. (2011) Mitochondrially targeted ceramide preferentially promotes autophagy, retards cell growth, and induces apoptosis. J. Lipid Res. 52, 278-88.
Morales AP, Carvalho AC, Monteforte PT, Hirata H, Han SW, Hsu Y-T, and Smaili SS. (2011) Endoplasmic reticulum calcium release engages Bax translocation in cortical astrocytes. Neurochem Res. 36, 829-38.
Molouki A, Hsu Y-T, Jahanshiri F, Abdullah S, Rosli R, Yusoff K. (2011) The matrix (M) protein of newcastle disease virus binds to human bax through its BH3 domain. Virol. J. 8, 385.
Chen YB, Aon MA, Hsu Y-T, Soane L, Teng X, McCaffery JM, Cheng WC, Qi B, Li H, Alavian KN, Dayhoff-Brannigan M, Zou S, Pineda FJ, O'Rourke B, Ko YH, Pedersen PL, Kaczmarek LK, Jonas EA, Hardwick JM. (2011) Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential. J. Cell Biol. 195, 263-76.
Ureshino R, Bertoncini C, Fernandes MJ, Abdalla F, Porto C, Hsu Y-T, Lopes G, and Smaili S. (2010) Alterations in calcium signaling and a decrease in Bcl-2 expression: A possible correlation with apoptosis in aged striatum. J. Neurosc. Res. 88, 438-47.
Molouki A, Hsu Y-T, Jahanshiri F, Rosli R, and Yusoff K. (2010) Newcastle disease virus infection promotes Bax redistribution to mitochondria and cell death in HeLa cells. Intervirology 53, 87-94.
Shen B, Gao L, Hsu Y-T, Bledsoe G, Hagiwara M, Chao L, and Chao J. (2010) Kallistatin attenuates endothelial apoptosis through inhibition of oxidative stress and activation of Akt-eNOS signaling. Am J Physiol Heart Circ Physiol. 299, H1419-27.
Jin J, Mullen TD, Hou Q, Bielawski J, Bielawska A, Zhang X, Obeid LM, Hannun YA, and Hsu Y-T. (2009) AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells. J. Lipid Res. 50, 2389-97.
Shen B, Smith RS, Hsu Y-T, Chao L, and Chao J. (2009) Kruppel-like factor 4 is a novel mediator of kallistatin in inhibiting endothelial inflammation via increased enos expression. J. Biol. Chem. 284, 35471-8.
Smaili SS, Rosenstock TR, and Hsu Y-T. (2008) Evaluation of some cell death features by real-time, real-space microscopy. Methods in Enzymol. 442, 27-50.
Teles AVF, Ureshino RP, Dorta DJ, Lopes GS, Hsu Y-T, Smaili SS. (2008) Bcl-xL inhibits Bax-induced alterations in mitochondrial respiration and calcium release. Neurosci. Lett. 442, 96-9.
Jin J, Hou Q, Mullen TD, Zeidan YH, Bielawski J, Kraveka JM, Bielawska A, Obeid LM, Hannun YA, and Hsu Y-T. (2008) Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells. J. Biol. Chem.39, 26509-26517.