Dorothy Hudig, Ph.D.

Department:   Microbiology and Immunology
Academic Unit:  School of Medicine
Title:  Professor
Professional degrees (Degree, year, Institution):  B.A., cum laude, 1968, Bryn Mawr College;  Ph.D., l977, University of Calif. San Diego

Contact Information

Mail Stop:   320
Phone:  774-4430
Fax:   327-2332
e-mail: dhudig@medicine.nevada.edu

Research Area(s)

Cancer biology, Immunology

Research Interests

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

Viki Elliott,
Ryan McKinney

Selected Publications

 (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.