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.
Closely associated with CPS is the Neutrophil Monitoring Laboratory (NML), a CLIA-certified facility in Frederick, Maryland, that supports the clinical and basic research of the NIAID Laboratory of Host Defenses and the NIAID Laboratory of Clinical Infectious Diseases. NML is headed by Douglas Kuhns, Ph.D. (contractor, Leidos Biomedical Research, Inc.), and performs genetic and functional studies on cells isolated from patients with recurrent bacterial and fungal infections, as well as patients with abnormal inflammatory responses.
Greenberg DE, Sturdevant DE, Marshall-Batty KR, Chu J, Pettinato AM, Virtaneva K, Lane J, Geller BL, Porcella SF, Gallin JI, Holland SM, Zarember KA. Simultaneous host-pathogen transcriptome analysis during Granulibacter bethesdensis infection of neutrophils from healthy subjects and patients with chronic granulomatous disease. Infect Immun. 2015 Nov;83(11):4277-92.
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 Dec 2;130(23):2031-9.
Chu J, Song HH, Zarember KA, Mills TA, Gallin JI. Persistence of the bacterial pathogen Granulibacter bethesdensis in chronic granulomatous disease monocytes and macrophages lacking a functional NADPH oxidase. J Immunol. 2013 Sep 15;191(6):3297-307.
Matharu K, Zarember KA, Marciano BE, Kuhns DB, Spalding C, Garofalo M, Dimaggio T, Estwick T, Huang CY, Fink D, Priel DL, Fleisher TA, Holland SM, Malech HL, Gallin JI. B-cell activating factor (BAFF) is elevated in chronic granulomatous disease. Clin Immunol. 2013 Aug;148(2):258-64.
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 Dec 30;363(27):2600-10.
Visit PubMed for a complete publication listing.
Comparison of Inflammatory Responses in Normal Volunteers and Patients With Abnormal Phagocyte Function Using the Suction Blister Technique (90-I-0120)
Non-Invasive Assessment of Atherosclerosis in Patients With CGD and Other Disorders of the Immune System (10-I-0029)
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Last Updated March 07, 2016