John I. Gallin, M.D.
Clinical Pathophysiology Section
Building 10, Room 2C202
10 Center Drive
Bethesda, MD 20892
The mission of the Clinical Pathophysiology Section is to study the genetic causes and the biological consequences of inborn diseases of phagocytic blood cells.
Chronic granulomatous disease (CGD) has been our major focus. CGD occurs in patients whose phagocytes (neutrophils and monocytes) are unable to generate antimicrobial levels of reactive oxygen species (e.g., superoxide anion) due to mutations in components of the NADPH oxidase as shown below.
Without sufficient production of superoxide anion, a key mediator of host defense, these patients suffer from life-threatening bacterial and fungal infections as well as tissue granuloma formation and other inflammatory diseases. Our section studies host and microbial determinants of pathogenesis by fungal (e.g., Aspergillus fumigatus) and bacterial (e.g., Granulibacter bethesdensis) causes of infection in CGD patients. Current work is focusing on the intracellular trafficking and persistence of this organism.
Genetic immunodeficiencies such as CGD also provide unique opportunities to study the roles of specific elements of the immune system in human health. For example, our clinical study employing non-invasive radiologic imaging of the cardiovascular system of CGD patients demonstrated a contribution of reactive oxygen species to the pathogenesis of atherosclerosis. Further studies are underway to evaluate the role of the NADPH oxidase in this important disease.
Dr. Gallin received his medical training at Cornell University Medical College in New York City followed by residency in internal medicine at Bellevue Hospital. In 1971, he first came to NIH as a clinical associate in Sheldon Wolff’s Laboratory of Clinical Investigation. In 1974 he served as senior chief resident in medicine at Bellevue Hospital before returning to NIH in 1976 as a senior investigator. Dr. Gallin has served as director of the NIAID intramural research program (1985–1994) and as chief of the Laboratory of Host Defenses (1991–2003). Since 1994, Dr. Gallin has also been director of the NIH Clinical Center. Among his honors are membership in the National Academy of Medicine and a master of the American College of Physicians.
Sibley CT, Estwick T, Zavodni A, Huang CY, Kwan AC, Soule BP, Long Priel DA, Remaley AT, Rudman Spergel AK, Turkbey EB, Kuhns DB, Holland SM, Malech HL, Zarember KA, Bluemke DA, Gallin JI. Assessment of atherosclerosis in chronic granulomatous disease. Circulation. 2014;130(23):2031-9.
Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, Uzel G, DeRavin SS, Priel DA, Soule BP, Zarember KA, Malech HL, Holland SM, Gallin JI. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600-10.
Zarember KA, Marshall-Batty KR, Cruz AR, Chu J, Fenster ME, Shoffner AR, Rogge LS, Whitney AR, Czapiga M, Song HH, Shaw PA, Nagashima K, Malech HL, DeLeo FR, Holland SM, Gallin JI, Greenberg DE. Innate immunity against Granulibacter bethesdensis, an emerging gram-negative bacterial pathogen. Infect Immun. 2012;80(3):975-81.
Kuhns DB, Fink DL, Choi U, Sweeney C, Lau K, Priel DL, Riva D, Mendez L, Uzel G, Freeman AF, Olivier KN, Anderson VL, Currens R, Mackley V, Kang A, Al-Adeli M, Mace E, Orange JS, Kang E, Lockett SJ, Chen, Steinbach PJ, Hsu AP, Zarember KA, Malech HL, Gallin JI, Holland SM. Cytoskeletal abnormalities and neutrophil dysfunction in WDR1 deficiency. Blood. 2016;128(17):2135-2143.
Kuhns DB, Hsu AP, Sun D, Lau K, Fink D, Griffith P, Huang DW, Priel DAL, Mendez L, Kreuzburg S, Zerbe CS, De Ravin SS, Malech HL, Holland SM, Wu X, Gallin JI. <i>NCF1</i> (p47<sup>phox</sup>)-deficient chronic granulomatous disease: comprehensive genetic and flow cytometric analysis. Blood Adv. 2019;3(2):136-147.
Related Scientific Focus Areas
Microbiology and Infectious Diseases
This page was last updated on April 9th, 2020