Immunopathogenesis Section
Steven M. Holland, M.D.
Chief, Immunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology
Director, Division of Intramural Research
Distinguished NIH Investigator
Major Areas of Research
Defects of phagocytes:
- GATA2 deficiency (MonoMAC syndrome)
- Disseminated nontuberculous mycobacterial infections
- Coccidioidomycosis
- Sarcoidosis
- Leukocyte adhesion deficiency
Program Description
The Immunopathogenesis Section takes a fully integrated approach to patients with infectious diseases, incorporating the molecular genetics of the host and the pathogen as well as mechanisms of pathophysiology. The integrated bench-to-bedside model is intrinsic to the Immunopathogenesis Section and is reflected in the entwining of prebaccalaureate, postbaccalaureate, M.D., and Ph.D. trainees in laboratory work and in the clinical appreciation of disease. When joined together, this team adds new insights into mechanisms of action and novel approaches to therapy. Active protocols in mycobacterial infections, Coccidioides infections and sarcoidosis are in progress, among others.
Biography
Education
M.D., 1983, The Johns Hopkins University School of Medicine
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 the National Institutes of Health in 1989 as a National Research Council fellow in the Laboratory of Molecular Microbiology, working in the laboratory of Dr. Sundararajan Venkatesan on transcriptional regulation of HIV. In 1991, Dr. Holland joined John Gallin’s 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. He was tenured in 2000. He was made Chief of the newly formed Laboratory of Clinical Infectious Diseases in 2004, where he served until 2016, when became Director of Intramural Research.
Clinical Trials
Detection and Characterization of Infections and Infection Susceptibility
Study of Mycobacterial Infections
Detection and Characterization of Host Defense Defects
Natural History of GATA2 Deficiency
Natural History of Coccidioidomycosis (Valley Fever)
Training Protocol on the Natural History of Tuberculosis
Selected Publications
Wang C, LaBere BA, Chinga MML, Harris AJ, Rosen LB, Rivera AE, Le Run E, Sacco KA, Ballan W, Woodward JV, Ostdiek SA, Smith MW, Anderson VL, Daub JR, Palmer CL, Kluczynski LC, Oler AJ, Walkiewicz MA, Ghosh R, Similuk M, Donovan FM, Witt J, Barros N, Wheat LJ, Galgiani JN, Freeman AF, Hsu AP, Zerbe CS, Holland SM. Interferon-γ therapy in patients with refractory disseminated coccidioidomycosis. Clin Infect Dis. 2025 May 29:ciaf286. doi: 10.1093/cid/ciaf286.
Udemgba C, Pillay B, Shafer S, Alberstadt A, Abers M, Gilliaux O, Chen K, Rae W, Hanitsch L, Von Bernuth H, Neves JF, Raje N, Moens L, van Hagen PM, Bergerson J, Hartog N, Niehues T, Dückers G, Falcone E, Keller M, Hsu A, Meyts I, Holland SM. IRF2BP2 deficiency: An important form of common variable immunodeficiency with inflammation. J Allergy Clin Immunol. 2025 Jun;155(6):2052-2062.e5. doi: 10.1016/j.jaci.2025.02.038
Le Run E, Tettelin H, Holland SM, Zelazny AM. Evolution toward extremely high imipenem resistance in Mycobacterium abscessus outbreak strains. Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0067324. doi: 10.1128/aac.00673-24.
Cheng A, Kashyap A, Salvator H, Rosen LB, Colby D, Ardeshir-Larijani F, Loehrer PJ, Ding L, Lugo Reyes SO, Riminton S, Ballman M, Rocco JM, Marciano BE, Freeman AF, Browne SK, Hsu AP, Zelazny A, Rajan A, Sereti I, Zerbe CS, Lionakis MS, Holland SM. Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency. N Engl J Med. 2024;390(12):1105-1117.
Sparks R, Rachmaninoff N, Lau WW, Hirsch DC, Bansal N, Martins AJ, Chen J, Liu CC, Cheung F, Failla LE, Biancotto A, Fantoni G, Sellers BA, Chawla DG, Howe KN, Mostaghimi D, Farmer R, Kotliarov Y, Calvo KR, Palmer C, Daub J, Foruraghi L, Kreuzburg S, Treat JD, Urban AK, Jones A, Romeo T, Deuitch NT, Moura NS, Weinstein B, Moir S, Ferrucci L, Barron KS, Aksentijevich I, Kleinstein SH, Townsley DM, Young NS, Frischmeyer-Guerrerio PA, Uzel G, Pinto-Patarroyo GP, Cudrici CD, Hoffmann P, Stone DL, Ombrello AK, Freeman AF, Zerbe CS, Kastner DL, Holland SM, Tsang JS. A unified metric of human immune health. Nat Med. 2024.
Ganapathi L, Cochran RL, Robbins GK, Barmettler S, Holland SM, Ababneh EI. Case 20-2024: A 73-Year-Old Man with Recurrent Fever and Liver Lesions. N Engl J Med. 2024;390(24):2309-2319.
Research Group
- Amanda Elias Riviera, B.S.
- Alexandra F. Freeman, M.D.
- Omar Gharib, B.S.
- Annalie Harris, B.S.
- Amy P. Hsu, Ph.D.
- Lavenda Kluczynski, M.Sc.
- Eva Le Run, Ph.D.
- Chi Ma, Ph.D.
- Beatriz Marciano, M.D.
- Glennys Reynoso, B.S., B.S.N.
- Lindsey Rosen, Ph.D.
- Samantha Shafer, B.S.
- Gulbu Uzel, M.D.
- Christa S. Zerbe, M.D.