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John I. Gallin, M.D.
Building 10-CRC, Room 6-2551
10 Center Drive
Bethesda, MD 20892-1504
Phone: 301-496-4114
Fax: 301-402-0244
jgallin@cc.nih.gov

Douglas B. Kuhns, Ph.D., Head, Neutrophil Monitoring Lab
Phone: 301-846-6378
doug.kuhns@fnlcr.nih.gov

Laboratory of Host Defenses

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Photo of John I. Gallin

John I. Gallin, M.D., M.A.C.P.

Chief, Clinical Pathophysiology Section, LHD
Director, Clinical Center, National Institutes of Health (NIH)

Major Areas of Research

  • Inflammation
  • Phagocyte dysfunction

 

 

 

Program Description

The mission of the Clinical Pathophysiology Section is to study the genetic causes and the biological consequences of inborn diseases of phagocytic blood cells.

illustrations of diseases of monocytes and neutrophils
Figure 1. The neutrophil and monocyte are the most abundant white blood cells in the circulation. Upon stimulation, they adhere to the endothelium and migrate into the tissues, where they seek and destroy pathogens. Disorder of cell signaling, granules, and oxygen metabolism have been described. The image depicts the various diseases of monocytes and neutrophils studied by the Clinical Pathophysiology Section, including leukocyte adhesion deficiency, IRAK4-deficiency, NEMO-deficiency, Job’s syndrome, secondary granule deficiency, Chediak-Higashi syndrome, myeloperoxidase deficiency, and all genotypes of chronic granulomatous disease (CGD).
Credit: NIAID

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.

illustration of amino acid mutations
Figure 2. This image shows the amino acid mutations in components of the NADPH oxidase that have been associated with chronic granulomatous disease (See Kuhns et al., NEJM 2010).
Credit: NIAID

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.

Genetic immunodeficiencies such as CGD also provide unique opportunities to study the roles of specific elements of the immune system in the pathogenesis of inflammatory diseases in human subjects. For example, one of our currently active clinical studies uses non-invasive radiologic methodology to evaluate the contribution of reactive oxygen species to the pathogenesis of cardiovascular disease. Another active component of our clinical program is the use of experimentally induced blisters to study the dynamic process of acute inflammation in human subjects.

Biography

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 American Society of Clinical Investigation, the Association of America Physicians, and the Institute of Medicine of the National Academy of Sciences and a master of the American College of Physicians.

Research Group

photo of group members
Left to right: Douglas Kuhns, Ph.D.; Jessica Chu, Ph.D.; John Gallin, M.D.; Anthony Pettinato, B.S.; Kol Zarember, Ph.D.

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.

Selected Publications

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.

Greenberg DE, Shoffner AR, Marshall-Batty KR, Arora K, Zhao M, Martin R, Ding L, Hammer CH, Shaw PA, Kuhns DB, Malech HL, Gallin JI, Zarember KA, Holland SM. Serologic reactivity to the emerging pathogen Granulibacter bethesdensis. J Infect Dis. 2012 Sep 15;206(6):943-51.

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 Mar;80(3):975-81

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.

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Last Updated June 27, 2014