Billy Tsai
Ph.D., Harvard, 1999
Assistant Professor
109 Zina Pitcher Place
3043 Biomedical Sciences Research Bldg (BSRB)
(734) 763 2547
email:btsai@umich.edu

Go to Billy Tsai's Research Lab

Interaction between host cell and pathogens

We use biochemical and cell biological approaches to understand the nature of interaction between different toxins and viruses with their host cell. Specifically, we are studying how cholera toxin and polyoma/SV40 virus hijack cellular machineries to cause disease. Both the toxin and viruses bind to receptors at the plasma membrane to initiate infection. The receptor-toxin or receptor-virus complex is endocytosed and traffic backwards along the secretory pathway to reach the lumen of endoplasmic reticulum (ER). From this compartment, these toxic agents are transported across the ER membrane into the cytosol. Once in the cytosol, cholera toxin induces a signaling cascade which leads to massive water secretion resulting in diarrhea. Polyoma and SV40 virus, upon reaching the cytosol, are transported into the nucleus where transcription and replication of the viral DNA genome ensue, leading to infection of the host cell. How the toxin and the viruses are transported from the cell surface to the ER and subsequently transported out of the ER into the cytosol are processes that remain largely mysterious.

Our overall goal is to clarify the cellular entry mechanism of both cholera toxin and polyoma/SV40 virus. Insight into the mechanisms will not only lead to a better understanding of how certain toxins and viruses infect their host cell, but will also clarify important aspects of basic cellular processes.

Recent publications

  1. Lencer, W.I and Tsai, B. (2003). The intracellular voyage of cholera toxin: going retro. Trends Biochem. Sci. 28, 639-645.
  2. Magnuson, B., Rainey, E.K., Benjamin, T., Baryshev,, M., Mkrtchian,, S., and Tsai, B. (2005). ERp29 triggers a conformational change in polyomavirus to stimulate membrane binding. Mol. Cell 20, 289-300.
  3. Low, J.A., Magnuson, B., Tsai, B., and Imperiale, M. J. (2006). Identification of gangliosides GD1b and GT1b as receptors for BK virus. J. Virology 80, 1361-1366.
  4. Forster, L.M., Sivick, K., Park, Y-N., Arvan, P., Lencer, W., and Tsai, B. (2006). Protein disulfide isomerase-like proteins play opposing roles during retro-translocation. J. Cell Biology 173, 253-259.
  5. Rainey-Barger, E.K., Mkrtchian, S., and Tsai, B. (2007). Dimerization of ERp29, a PDI-like protein, is essential for its diverse functions. Mol. Biol. Cell 18, 1253-1260.
  6. Tsai, B. Penetration of non-enveloped viruses into the cytoplasm. (2007). Annu. Rev. Cell Dev. Biol. 23, 23-43.
  7. Rainey-Barger, E.K., Magnuson, B., and Tsai, B. (2007). A chaperone-activated non-enveloped virus perforates the physiologically relevant ER membrane. J. Virology 81, 12996-13004.
  8. Lam, A.D., Tryoen-Toth, P., Tsai, B., Vitale, N., and Stuenkel, E.L.  SNARE-catalyzed fusion events are regulated by syntaxin1A-lipid interactions. Mol. Biol. Cell 19, 485-497.
  9. Bernardi, K.M., Forster, M.L., Lencer, W.I. and Tsai, B.  Derlin-1 facilitates the retro-translocation of cholera toxin. Mol. Biol. Cell 19, 877-884.