Gale A. Granger

Professor, Molecular Biology and Biochemistry
School of Biological Sciences


Other not listed

PH.D., University of Washington

Phone: (949)824-6045
Fax: (949) 824-8551
Email: gagrange@uci.edu

University of California, Irvine
3236 BS II
Mail Code: 3900
Irvine, CA 92697

picture of Gale A. Granger

Research
Interests
Tumor Immunology, Immunotherapy, Cellular Immunology, Cytokines
   
Research
Abstract
Lymphoid cells of the immune system are responsible for much of the destruction of cells and tissues which occur in allograft rejection, tumor immunity and autoimmune diseases. The first step in all these reactions occurs when lymphoid cells enter the tissue and recognize the cells to be destroyed via interaction of membrane receptors on both cell types. It is membrane interaction which induces the lymphoid cell to become "activated." As a result of activation, the lymphoid cells secrete proteins termed "cytokines" and the cytokines orchestrate the events that result in tissue destruction.


The interaction of solid tumors with the host immune systemic is complex, as the tumor cells can actively evade and suppress the immune system. Tumors can evade recognition by host lymphoid cells by down-regulating the expression of membrane proteins necessary to induce activation of the lymphoid cell. In addition, tumors can actively suppress the host immune system by secreting materials that both inhibit cellular activation (TGF-beta) and inhibit cytokine action (soluble cytokine receptors and cytokine receptor antagonists).


Dr. Granger's studies are divided into two areas: (1) How tumors suppress the host immune system; and (2) developing new immune based therapies for treating patients with incurable cancers.


The cytokine TNF is released by activated lymphoid cells and is key in the orchestration of tumor cell destruction. This laboratory discovered and is examining the mechanisms of how animal and human tumor cells produce and release soluble forms of TNF membrane receptors which block TNF activity. Studies examine the cell and molecular mechanisms of how release of membrane receptors occurs and how the process is controlled. These studies are conducted with human and animal tumor cells in vitro systems.


The second area of research is to develop new immune-based therapies for treating patients with incurable cancers. Information derived from basic research is first translated into a trial therapy to determine if it will induce tumor regression in animals bearing experimental tumors. A therapy that yields positive results from animal testing can then be translated into clinical trials in human cancer patients. Research in this laboratory has focused on developing new therapies for patients with incurable brain, pancreatic and ovarian cancers. Two types of therapies are currently under study: (1) intratumor implants with activated lymphoid cells; and (2) genetically engineered tumor vaccines. Very encouraging results have been obtained with intratumor implants in patients with brain or pancreatic cancers. While tumor vaccines have given promising results in animals clinical programs in have just been initiated and it is to early to comment on results.
   
Publications Yamamoto, R.S., C. Ware, and G.A. Granger (1986). The Human LT system XI: Identification of LT and TNF-like Lt forms from Stimulated Natural Killers, Specific and Nonspecific Cytotoxic Human T cells in vitro. J. Immunol.
137:1878-1884.
   
  Kobayashi, M., M. Plunkett, I. Masunaka, R.S. Yamamoto, and G.A. Granger (1986). The Human LT system XII: Purification and functional studies of LT and TNF-like LT forms from a continuous human T cell line that resembles LT forms from human cytolytic T cells. J. Immunol., 137:18891892.
   
  Averbook, B., T. Ulich, S. Orr, R.S Yamamoto, I. Masunaka, and G.A. Granger (1986). Human Lymphotoxin, Macrophage Toxin and Tumor Necrosis Factor: An Inter-related Family of Proteins that Mediate InSammation, Cellular
Activation, Lipid Metabolism, Coagulation, and Tumor Necrosis. In Biological Response Modifiers. Dicky Jen Wei Chiao, Ed. Marcel Dekker, Publ.
   
Professional
Societies


   
Graduate Programs Immunology and Pathogenesis

Biotechnology

   
Research Center Biological Sciences, Clinical Cancer Center
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=2162
   
Last updated 08/18/2000