Dorothy Hudig, Ph.D.
Department: Microbiology and Immunology
Academic Unit: School of Medicine
Professional degrees (Degree, year, Institution): B.A., cum laude, 1968, Bryn Mawr College; Ph.D., l977, University of Calif. San Diego
Mail Stop: 320
Cancer biology, Immunology
Sometimes death is the only answer. The body benefits when virally infected cells are eliminated before the viruses can replicate further. The body also benefits when tumor growth is curtailed. Cytotoxic T and natural killer (NK) lymphocytes are potent killer cells that eliminate these unwanted cells. The process can take minutes or days, depending on the biochemistry of the processes. My laboratory pioneered the study of cytotoxic proteases termed granzymes that are stored in cytotoxic granules of the killer lymphocytes. The granzymes, together with a pore-forming protein called perforin, are one potent means of killing cells within minutes or hours. Perforin permeabilizes cell membranes to kill cells directly or to promote entry of granzymes, while different granzymes have critical substrates both inside and outside of the cells that will die. The biochemistry of these proteins is of great interest because it is difficult to damage a lipid membrane and because only very selective substrates will initiate apoptosis. We are now studying the biochemistry of additional, slower forms of lymphocyte killing, including lipid and lipase-dependent mechanisms. So, if the first mechanism doesn’t kill ‘em, the next one will. We are alive only because we can control infections and tumors. Thank the biochemistry of your immune system!
Current Graduate Students
David L. Tamang, Ph.D., CMB 2008
Bryce N. Alves, Ph.D., CMB 2009
Other Lab Members
(a highly cited paper) Redelman, D., and Hudig, D. The mechanisms of cell-mediated cytotoxicity I. Killing by murine cytotoxic T lymphocytes requires cell surface thiols and activated protease. J. Immunol. l24:870-878, l980. PMID: 6965393
Tamang, D.L., Alves, B.N., Elliott, V., Redelman, D., and Hudig, D. Low dose IL-15 induces snap arming of CD44low T lymphocytes in the absence of antigen. Cellular Immunology 251: 93-102, 2008. PMID: 18485336
Tamang, D.L., Alves, B.N., Elliott, V., Redelman, D., Wadhwa, R., Fraser, S.A., and Hudig, D. Inhibition of perforin-mediated lysis by protein disulfide isomerase associated with cytotoxic T cell granules. Cellular Immunology 255: 82-92, 2009. PMID: 19147124
Alves, B., Leong, J., Tamang, D.L., Elliott, V., Lowe, M.E. and Hudig, D. Hydrolysis of tumor cell lipids after cytotoxic T lymphocyte (CTL)-mediated death. Accepted, International Immunology. PMID: 19325035
Alves, Bryce N., Marshall, K., Tamang, D.L., Leong, J., Redelman, D., Elliott V., Lowe, M. E., and Hudig, D. Lipid-dependent cytotoxicity by the lipase PLRP2 and by PLRP2-positive cytotoxic T lymphocytes (CTLs). Accepted, Cell Biochemistry and Function.
Faculty by research area
- Mastick, C
- Mastick C.
- Mastick G.
- Van der Linden
- von Bartheld
- von Bartheld