Laboratory of Clinical Infectious Diseases

Steven M. Holland, M.D.

Tenured Investigator

Immunopathogenesis Section

Dr. Holland received his M.D. from the Johns Hopkins University School of Medicine in 1983, where he stayed as a resident in internal medicine, assistant chief of service in medicine, and fellow in infectious diseases. He came to NIH in 1989 as a National Research Council fellow in the Laboratory of Molecular Microbiology, working on transcriptional regulation of HIV. In 1991, Dr. Holland joined the Laboratory of Host Defenses, shifting his research to the host side, with a focus on phagocyte defects and their associated infections. His work centered on the pathogenesis and management of chronic granulomatous disease, as well as other congenital immune defects affecting phagocytes, including those predisposing to mycobacterial diseases. In 2004, he became chief of the LCID.

Description of Research Program

The Immunopathogenesis Section’s therapeutic and research programs take a fully integrated approach to infectious disease, incorporating the molecular genetics of the host and the pathogen as well as mechanisms of pathogenesis that allow the development and study of novel therapeutics. The integrated bench-to-bedside model is intrinsic to the Immunopathogenesis Section’s approach and is reflected in the close involvement of trainees (both M.D. and Ph.D.) in laboratory work and in the clinical appreciation of disease, which together add new insights into mechanisms of action and avenues of therapy. New protocols in staphylococcal infections, idiopathic CD4 lymphocytopenia, and drug-resistant tuberculosis are in progress.

Major Areas of Research

• Immune defects of phagocytes: chronic granulomatous disease, hyper IgE (Job’s) syndrome, leukocyte adhesion deficiency
• Cytokines in the pathogenesis and therapy of infections
• Susceptibility to disseminated mycobacterial infections, such as autoantibodies to interferon gamma and defects in the interferon gamma/IL-12 pathway
• Mechanisms of mycobacterial pathogenesis
• Mechanisms of bacterial pathogenesis (e.g., Burkholderia)
• Mechanisms of airway dysfunction

Current Clinical Protocols

• A Double-Blind, Randomized, Placebo-Controlled Cross-Over Study Assessing the Role of Pathogen-Specific IgE and Histamine Release in the Hyper-IgE Syndrome and the Effect of Ranitidine on Laboratory and Clinical Manifestations
• Screening Protocol for Detection and Characterization of Infections and Infection Susceptibility
• Pilot Study of Omalizumab (Xolair) in Hyper IgE (Job's) Syndrome
• Natural History, Genetics, Phenotype, and Treatment of Mycobacterial Infections
• Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection (Job) Syndrome
• Detection and Characterization of Host Defense Defects
• Research Respiratory Tract Procedures in Healthy Adult Volunteers and Adult Patients to Obtain Specimens for In Vitro Analyses of Infection Pathogenesis and Susceptibility
• Genetic Disorders of Mucociliary Clearance
• A Study of Adjuvant Cytokine Therapy in Pulmonary Mycobacterium Avium Complex Infection
• Evaluation of Immune Response to Vaccines in Primary Immune Disorders

Research Group Members

Sarah K. Browne, M.D.; Rhonda Colombo, M.D.; Li Ding, M.D.; Alexandra F. Freeman, M.D.; David E. Greenberg, M.D.; Xeumeng Han-Sarro, Ph.D., M.D.; Jennifer Heimall, M.D.; Amy P. Hsu, B.A.; Kenneth N. Olivier, M.D.; Michelle Paulson, M.D.; Elizabeth P. Sampiao, M.D., Ph.D.; Gulbu Uzel, M.D.; Donald Vinh, M.D.; Adrian Zelazny, Ph.D.

Selected Publications

To view a complete listing, visit PubMed.

Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schäffer AA, Puck JM, Grimbacher B. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007 Oct 18;357(16):1608-19.

Uzel G, Tng E, Rosenzweig SD, Hsu AP, Shaw JM, Horwitz ME, Linton GF, Anderson SM, Kirby MR, Oliveira JB, Brown MR, Fleisher TA, Law SK, Holland SM. Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1). Blood. 2008 Jan 1;111(1):209-18.

Siddiqui S, Anderson VL, Hilligoss DM, Abinun M, Kuijpers TW, Masur H, Witebsky FG, Shea YR, Gallin JI, Malech HL, Holland SM. Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis. 2007 Sep 15;45(6):673-81.

Freeman AF, Holland SM. Persistent bacterial infections and primary immune disorders. Curr Opin Microbiol. 2007 Feb;10(1):70-5.

Greenberg DE, Ding L, Zelazny AM, Stock F, Wong A, Anderson VL, Miller G, Kleiner DE, Tenorio AR, Brinster L, Dorward DW, Murray PR, Holland SM. A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease. PLoS Pathog. 2006 Apr;2(4):e28.

Patel SY, Ding L, Brown MR, Lantz L, Gay T, Cohen S, Martyak LA, Kubak B, Holland SM. Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections. J Immunol. 2005 Oct 1;175(7):4769-76.

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