Mary C. Dinauer, MD, PhD Nora Letzter Professor of Pediatrics
Nora Letzter Professor of Pediatrics: Department of Pediatrics
Clinical Section: Pediatric Hematology/Oncology
Fellowship: Pediatric Hematology/Oncology, Harvard Medical School, The Children's Hospital and Dana Farber Cancer Institute
Residency: Univ. of California, San Francisco, CA
MD: University of Chicago, 1981
PhD: University of Chicago, 1979
Current Research Interests:
Oxidant production by neutrophil and macrophage NADPH oxidase; innate immunity and inflammation; gene therapy of inherited hematopoietic disorders.
Dinauer's laboratory interests include characterization of the phagocyte respiratory burst oxidase and its role in human disease as well as gene therapy of inherited hematopoietic disorders. Genetic defects in this superoxide-generating NADPH oxidase result in chronic granulomatous disease (CGD), a recessive inherited disorder characterized by an absent respiratory burst and recurrent, and often life-threatening infections. Phagocyte oxidant production is essential for microbial killing, and increasingly recognized to regulate the inflammatory response and adaptive immunity. The excessive release of oxidants also contributes to tissue injury in a variety of inflammatory disease states. The active oxidase complex includes a membrane bound NOX2 flavocytochrome that is the catalytic core, soluble regulatory proteins and Rac-GTP. Ongoing projects include characterization of functional domains within NADPH oxidase subunits and signaling cascades that converge to activate this enzyme during inflammation and phagocytosis of microbes. These questions are being studied using a combination of molecular and cell biology approaches and animal models, including mice generated by gene targeting. Other studies focus on the development of gene replacement therapy for X-linked CGD, utilizing viral vectors to introduce the corrective gene into murine and human hematopoietic stem cells.