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The Risma Lab researches natural killer (NK) cell and cytotoxic T lymphocyte (CTL) function and the relationship between NK cell/CTL killing and disease. NK cell and CTL function are critical to immune homeostasis, and NK cells and CTLs rely on a variety of methods to kill target cells. Our primary interest is in the perforin-granzyme–mediated pathway of cell death whereby preformed cytotoxic granules are degranulated from NK cells/CTLs at the immune synapse and initiate apoptosis via granzyme delivery to target cells. When this pathway is defective, the immune response to virally infected cells or tumor cells is impaired. The consequence of absent NK cell/CTL function in children is the development of a fatal, inflammatory disorder called hemophagocytic lymphohistiocytosis (HLH). My laboratory uses basic, translational, and genetic research approaches to explore the relationship between defects in lymphocyte cytotoxicity and the pathogenesis of HLH, specifically as it relates to mutations in the gene encoding perforin. By studying this rare disease, we are gleaning insights into the mechanisms by which NK cells/CTLs kill target cells, allowing us to apply our findings to more common diseases such as chronic viral infections and malignancies.
We have established a unique, multidisciplinary research team to accomplish our goals. Team members include: Dr. Janos Sumegi, who is interested in novel genetic etiologies for HLH; Dr. Michael Jordan, who is determined to understand the pathogenesis of HLH in virally infected, perforin-deficient mice; and other team members, such as Dr. Alexandra Filipovich, Dr. Jack Bleesing, Dr. Rebecca Marsh and Dr. Ashish Kumar, who all have critical roles in diagnosis and treatment of patients, development of new therapeutic protocols, and recruitment of patients to HLH research studies. We engage in a monthly Histiocytosis Research Conference led by Dr. Risma and a monthly clinical conference, led by Dr. Kumar.
Dr. Risma serves as the Educational Director of the Division of Allergy and Immunology and the Fellowship Director of the Allergy/Immunology Fellowship Program.
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