Laboratory of Host Defenses
John I. Gallin, M.D.
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 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 scientific 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 been director of the NIH Clinical Center. Dr. Gallin has numerous honors, including being a master of the American College of Physicians and being elected to membership of the Association of American Physicians, the American Society of Clinical Investigation, the American Association of Immunologists, and the Institute of Medicine of the National Academy of Sciences.
Description of Research Program
The mission of the Clinical Pathophysiology Section is to study the genetic causes and the biological consequences of inborn diseases of phagocytic blood cells.
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
Among these, 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.
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. We also perform clinical and laboratory studies of patients with CGD or other immunodeficiencies shown above to better understand the regulation of inflammation and the immune system in human subjects.
Research Group Members
Left to right: Douglas Kuhns, Ph.D.; Jessica Chu, Ph.D.; Kol Zarember, Ph.D.; John Gallin, M.D.; Helen Song, B.S.
Closely associated with CPS is the Neutrophil Monitoring Laboratory (NML), a CLIA-certified facility in Frederick, MD, 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, SAIC-Frederick, 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.
Clinical Research Protocols
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)
Assessment of the Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease (10-I-0123)
Selected Recent Publications
(View complete list in PubMed.)
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.
De Ravin SS, Zarember KA, Long-Priel D, Chan KC, Fox SD, Gallin JI, Kuhns DB, Malech HL. Tryptophan/kynurenine metabolism in human leukocytes is independent of superoxide and is fully maintained in chronic granulomatous disease. Blood. 2010 Sep 9;116(10):1755-60.
Singh A, Zarember KA, Kuhns DB, Gallin JI. Impaired priming and activation of the neutrophil NADPH oxidase in patients with IRAK4 or NEMO deficiency. J Immunol. 2009 May 15;182(10):6410-7.
Zarember KA, Cruz AR, Huang CY, Gallin JI. Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus. Antimicrob Agents Chemother. 2009 Jun;53(6):2654-6.
Kuhns DB, Priel DA, Gallin JI. Induction of human monocyte interleukin (IL)-8 by fibrinogen through the toll-like receptor pathway. Inflammation. 2007 Oct;30(5):178-88.
Zarember KA, Sugui JA, Chang YC, Kwon-Chung KJ, Gallin JI. Human polymorphonuclear leukocytes inhibit Aspergillus fumigatus conidial growth by lactoferrin-mediated iron depletion. J Immunol. 2007 May 15;178(10):6367-73.
