- Theofilopoulos, Argyrios Leader
Scripps Clinic's research program began in the fledgling field of immunopathology in the early 1960s. The small group of investigators who came to the Institute at that time were primarily interested in the underlying biology of autoimmune diseases and immunologic diseases. Their initial studies were highly successful and developed a conceptual framework to explain how normal, but inappropriate, immune reactions can give rise to both local and inflammatory diseases. The research program in immunology expanded rapidly and soon included basic investigations of both the innate and acquired immune systems, cancer immunology, immunology of infectious diseases and intracellular signaling mechanisms used by cells of the immune system.
Over the years, the Scripps Research Immunology program has become recognized as one of the world's leading centers for the study of autoimmune disorders. Groundbreaking work has been accomplished in the structure and function of key proteins of the immune system found in both the plasma and on cell membranes. Thus the focus on diseases where immune complexes play a central role has evolved to the present department comprised of scientists with broad efforts in many aspects of immunology.
Basic studies of the immune system include the stimulation, control, and biochemistry of inflammation (the first line of defense against infection); the genetics of the antibody response; T-cell immunity, including antigen presentation, thymic selection, and receptor signaling; and tolerance induction and autoimmunity.
Among the areas receiving attention within the department are the identification of genes that predispose individuals to immunologic disease such as autoimmune disease or diabetes. Such efforts require expertise in molecular genetics, cell biology and studies in animal models of disease. Others in the department are studying the causal link between vascular disease, including atherosclerosis, and the immune system. Another important research area involves the definition of structure and function of key proteins in both the innate and acquired immune systems. This is accomplished through application of the most advanced biophysical, biochemical and molecular biological approaches. Another important technological advance is being utilized to isolate and screen virtually the entire antibody repertoire of humans or other mammals and then to recover scientifically and clinically important clonal antibodies. Such approaches promise to yield novel antibodies with therapeutic potential in infectious disease.
The development of the cells of the immune system -- both B and T lymphocytes -- represents a challenging problem in developmental biology. Here, these issues have been attacked by combining novel transgenic animal models together with sophisticated analysis of gene expression and cellular function. This effort is aided tremendously by the advanced flow cytometry facilities of the research institute. Studies of the molecular pathology of HIV infection occupy the attention of a large number of immunologists here. Their efforts promise new insights into the devastating disease caused by this virus.
Because of the immune system's role in regulating the survival of malignant cells, many members of the department have focused their investigations on various aspects of cancer biology and immunology. These efforts include a more in-depth understanding of the mechanisms by which lymphocytes kill tumor cells, an analysis of the relationship between the coagulation system and tumor cell metastases, and the development of novel approaches to controlling or eliminating malignant tumors such as monoclonal antibodies conjugated with cytotoxic agents and compounds that inhibit the process of angiogenesis. Collectively, these efforts in cancer biology promise to yield new approaches to therapy.
In addition, several members of the department have important advances in the area of intracellular signal transduction mechanisms. Their accomplishments include the discovery of new molecules in the family of low molecular weight GTP-binding proteins and in the MAP kinases pathways. Both of these efforts help explain how cells of the immune system regulate most essential functions.
From its rather modest beginning, the Department of Immunology and Microbial Science has evolved into a multifaceted discipline at The Scripps Research Institute. Its diverse group of researchers bring together a formidable array of scientific talents to address today's most important, unanswered questions in immunology.