role played by neutrophils in killing bacteria and fungi. Major areas of research Segal has had diverse research interests. His major discoveries have been: A. The NADPH oxidase and causes of Chronic Granulomatous Disease (CGD) 1. The identity of the NADPH oxidase that generates superoxide in myeloid cells. He showed it to be a low potential flavocytochrome, and demonstrated that mutations in the gene coding for it, and for its activating proteins, cause the severe immunodeficiency disease of Chronic Granulomatous Disease (CGD). 2. He showed that the mechanism by which microbes are killed within the phagocytic vacuole of neutrophils is not through the toxic actions of oxygen free radicals or through the generation of HOCl by myeloperoxidase. The oxidase elevates the pH within the phagocytic vacuole, and drives potassium into this compartment to compensate the charge generated across the membrane by the passage of electrons. The elevated pH and potassium concentration activate the neutral proteases, cathepsin G and elastase, which kill and digest the microbes. 3. He determined the causes of Crohn's disease, a chronic granulomatous inflammation that predominantly affects the terminal small bowel and colon. He demonstrated that the common underlying pathogenesis of this condition is a failure of acute inflammation as a consequence of which faecal material gaining access through the mucosa of the bowel is not cleared from the tissues, where it festers, resulting in the characteristic chronic inflammation. Publications >300 publications H-Index 75| NADPH oxidase and Chronic Granulomatous Disease Microbial killing Cause of Crohn's Disease References 1944 births Fellows of the Royal Society Fellows of the Academy of Medical Sciences (United Kingdom) British Jews South African Jews Jewish scientists Living people British biochemists Academics of University College London University of Cape Town alumni Alumni of the University of London