Chairman's Overview

The Department of Immunology has six full Staff members (Drs. Thomas Hamilton, Robert Fairchild, James Finke, Peter Heeger, Andrew Larner, and Vincent Tuohy), threeAssociate Staff (Drs. Xiaoxia Li, Lina Lu and Shiguang Qian) and one Assistant Staff (Dr. Booki Min). In addition, nine investigators hold primary departmental appointments in clinical divisions: Drs. Ashok Aggarwal (Urological Institute), Ronald Bukowski (Taussig Cancer Center, Hematology-Oncology), Peter Cohen, Greg Plautz (Center for Surgery Research), Raymond Tubbs, Belinda Yen-Lieberman (Clinical Pathology), Anthony Stallion (Pediatric Surgery), Victor Perez (Eye Institute), and Maria Siemionow (Plastic Surgery). These investigators participate in substantial collaborative interactions with colleagues holding primary appointments in Immunology and thereby serve as important liaisons between the laboratory bench and the clinical setting.

Research programs within the Department of Immunology are pursued within two broad themes. The first includes studies of T-cell development and function at the cellular and molecular levels, using a variety of disease models. Areas of focus include the recruitment and function of specific T-cell subsets at sites of immune-mediated inflammation, the development and evolution of specific T-cell populations in autoimmune disease, the suppression of T-cell responses in cancer patients, and the homeostatic regulation of lymphocyte number and antigen specificity.

The second theme centers on the regulation and function of the innate immune system. Specific programs include the mechanisms of IFN-mediated signaling, regulation of gene expression at inflammatory sites, the biochemistry and enzymology of nitric oxide synthases, the identification and characterization of mammalian anti-microbial peptide genes, and intracellular signaling pathways involved in regulating innate immune responses.

These broad themes provide remarkable opportunities for interaction among the individual laboratories and together represent a concept which integrates the department as a whole: the interface between innate and acquired immunity and the resulting complexity of immune-mediated inflammation. This concept appears to be highly relevant in a spectrum of clinically important entities that have either acute or chronic inflammation as a key causative or symptomatic feature of pathogenesis.

Recent highlights include the following observations and discoveries:

• Demonstration of mechanistic heterogeneity involved in regulated control of mRNA stability (Hamilton laboratory)
• Successful development of two mouse knockouts leads to identification of specific roles for important signaling pathway components mediating immune/inflammatory disease: ACT1 and SIGRR (Li laboratory)
• Dissection of tumor-derived ganglioside induced mechanisms of apoptosis in T cells (Finke laboratory)
• Identification of the regulatory function of the commplement system in controlling acquired immunity (Dr. Heeger laboratory)
• Demonstration that components of innate and adaptive (i.e. antigen-specific) immunity cross regulate alloantigen response in organ transplantation and contact hypersensitivity responses in the skin. (Fairchild laboratory)
• Development of new animal models of autoimmunity resulting in disorders in heart function, hearing, and reproductive capacity (Dr. Tuohy laboratory)
• New characterization of the mechanisms regulating lymphocyte homeostasis for cell number and specificity (Dr. Min laboratory)

Additional Cleveland Clinic sites related to problems that have immunologic components: