Research Interests:
Natural killer and T cytotoxic lymphocytes kill tumor and virus-infected cells by means of pore-forming proteins that are released from specialized granules of the killer lymphocytes. Granule-mediated lysis of cells is augmented by the activities of a newly discovered family of serine-dependent proteases, termed granzymes that are found in the cytotoxic granules. My laboratory was among the first to recognize the role of these serine proteases in killing (1980). We continue to study these enzymes and their roles in cell death. Recently, we have begun two new studies, one of the effects of IL-15 and other cytokines on cytotoxic T cell activity and the other on the function of an inducible lipase found in cytotoxic CD8+ T lymphocytes.

Current research projects:
We have started a new project, characterizing the roles of lipases in T cell-mediated cytotoxicity. Pancreatic lipase-related protein 2 (PLRP2), a digestive lipase found in the gut, is also expressed by CD8 T cells when they are induced by IL-4. Wild-type cytotoxic T lymphocytes are more lytically active than PLRP2-/- T cells. We are working to determine how this lipase participates in cell death.

Graduate students:
David Tamang, CMB Ph.D. Program, Fall 2002-present.
Bryce Alves, CMB Ph.D. Program, Fall 2003-present

Grants:
PI, NIH CA R01 CA38942
Director, NIH T32 CA09563

Selected Publications (from over 70):
Hudig, D., Ewoldt, G.R., and Woodard, S.L.. "Proteases and Lymphocyte Cytotoxic Killing Mechanisms". In Innate Immunity, edited by Jay Unkeless and Sam Wright. Curr. Opin. in Immunol. 5: 90 96, 1993.

Ewoldt, G.R., M.J. Smyth, P.K. Darcy, J.L. Harris, C.S. Craik, B. Horowitz, S.L. Woodard, J.C. Powers, and D. Hudig. RNKP 4 and RNKP 7, new granzyme serine proteases expressed in activated rat lymphocytes. J. Immunol. 158: 4574 4583, 1997.

Woodard, S.L., Fraser, S.A., Winkler, U., Powers, J.C., and Hudig, D. Purification and characterization of Chymase 1, a granzyme that participates in perforin lysis. J. Immunol. 160: 4988 4993, 1998.

Korver, G.E., C-M Kam, J.C. Powers and D. Hudig. Dipeptide vinyl sulfones suitable for intracellular inhibition of dipeptidyl peptidase I. Int. Immunopharmacol. 1: 21-32, 2001.

Tran, T.V., Ellis, K.A., Kam, C-M., Hudig, D., and Powers, J.C. Dipeptidyl peptidase I: Importance of progranzyme activation and other dipeptide sequences and the n-terminal amino group of synthetic substrates for enzyme activity. Arch. Biochem. Biophys., 403: 160-170, 2002.

Tran, T.V., Ellis, K.A., Kam, C-M., Hudig, D., and Powers, J.C. Dipeptidyl peptidase I: Importance of progranzyme activation and other dipeptide sequences and the n-terminal amino group of synthetic substrates for enzyme activity. Arch. Biochem. Biophys., 403: 160-170, 2002.

Baroa, I., D. Hudig, and J. Ascensao. IL-15-mediated induction of LFA-1 is a late step required for cytotoxic differentiation of human NK cells from CD34+Lin? bone marrow cells. J. Immunol. 171: 683-690, 2003.

Kam, C-M, Marion, Korver, G.E., McGuire, M., Thiele, D., Hudig, D. and Powers, J.C. Design and Evaluation of Inhibitors for Dipeptidyl Peptidase I, Archives of Biochemistry and Biophysics. 427: 123-134, 2004.

Choy, J.C., R.P. Cruz, A. Kerjner, J. Geisbrecht, T. Sawchuk, S.A. Fraser, D. Hudig, R.C. Bleakley, F.R. Jirik, B.M. McManis and D. J. Granville. Granzyme B induces endothelial cell apoptosis and contributes to the development of transplant vascular disease. Am J Transplant. 5(3):494-9, 2005.

Woolard, M.D., Hudig, D., Tabor, L., Ivey, J.A., and Simecka, J.W. NK cells in gamma-interferon-deficient mice suppress lung innate immunity against Mycoplasma spp. Infect Immun. 73(10):6742-51, 2005.

Tamang, D., Redelman, D., Alves, B.N., Vollger, L., Bethley, C., and D. Hudig. Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: Multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal. Cytokine 36: 148-159, 2006.