• Immunology - Mechanisms of action and therapeutic potential of tumor specific cytotoxic T lymphocytes
• Development of vaccines that stimulate CTL
• Utilizing CD95 (Fas) ligand to suppress tumors and cell-mediated immune responses

• Assays of helper and cytotoxic T cell responses
• Assays of apoptosis including morphology, DNA damage and flow cytometric analysis

• Leon R, Hedlund T, Meech SJ, Li S, Schaack J, Hunger S, Duke R, and DeGregori J. 1998. Adenoviral mediated gene transfer in lymphocytes. Proc. Natl. Acad. Sci. USA 95:13159.

• Desbarats J, Duke RC, and Newell MK. 1998. Novel role of Fas ligand in cell cycle arrest of CD4+ T cells. Nature Med. 4:1377.

• Hedlund TE, Schaack JB, Meech SJ, Srikanth S, Kraft AS, Miller GJ, and Duke RC. 1999. Adenovirus-mediated expression of Fas ligand induces apoptosis of human prostate cancer cells. Cell Death Differ. 6:175.

• Bellgrau D and Duke RC. 1999. Apoptosis and CD95 ligand in immune privileged sites. Int. Rev. Immunol. 18:547.

• Nelson D, Setser E, Akanbi A, Hall DG, Kledvitsky R, Oskinaska H, Bellgrau D, Duke RC, and Robbins J. 2000. Pro-inflammatory consequences of transgenic Fas ligand expression in the heart. J. Clin Invest. 105:1199.
• Duke RC. 2000. Methods of analyzing chromatin changes accompanying apoptosis of target cells in killer cell assays. Methods Mol. Biol. 121:125.

• Stubbs AC, Franzusoff A, Martin KS, Coeshott C, Skaates SV, Bellgrau D, Duke RC, and Wilson CC. 2001. Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity. Nature Med. 5:625.

• Meech SJ, Edelson R, Norris DA, Walsh P, and Duke RC. 2001. Reversible resistance to apoptosis in cutaneous T cell lymphoma (CTCL). New York Acad. Sci. (in press).

• Member, Governor’s Council on Biotechnology
• Member, Colorado Association of Biotechnology
• President and CEO, GlobeImmune, Inc.

LAY SUMMARY OF RESEARCH OBJECTIVES:

Our laboratory is interested in understanding the biology and mechanisms of action of cytotoxic T lymphocytes (CTL). The major role of the CTL in the immune system is to kill cells infected with viruses. We are using recombinant Baker’s yeast expressing HIV proteins as a vaccine to stimulate CTL in HIV-infected patients. In addition, CTL are involved in regulation of immune responses because they express a ligand for CD95 (Fas/APO-1). CD95 is expressed on activated B and T cells. Our data indicate that CTL can kill CD95-bearing activated lymphocytes and thereby prevent transplant rejection and the development of autoimmunity and perhaps lymphoid malignancies. Our findings suggest that CD95 ligand could be used for indications in which immunosuppressive agents are currently used. These include prevention of transplant rejection as well as therapies for inflammatory/autoimmune diseases and leukemia/lymphoma.

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