Alan Sher, Ph.D.

Deputy Chief, Laboratory of Parasitic Diseases
Chief, Immunobiology Section

Major Areas of Research

  • Mechanisms of host resistance and immune regulation in parasitic and mycobacterial infection
  • Role of innate pathogen recognition in the initiation of adaptive immunity and in CD4+ T-cell subset effector choice
  • Regulatory pathways limiting pathogen-induced Th1 immunopathology
  • Immunotherapeutic approaches to the treatment of infectious disease

Program Description

The Immunobiology Section studies host resistance and immune regulation in parasitic and other infections of global importance. The ultimate goal of this work is immunologic disease intervention in the form of vaccination or immunotherapy. At the same time, our research on the host response to infection has provided insights into the effector functions and regulatory mechanisms used by the vertebrate immune system and in the role of innate pathogen recognition in these processes. Much of the work of the section is focused on the immunologic analysis in murine models of diseases induced by parasitic and bacterial agents (e.g., Toxoplasma gondiiMycobacterium spp.), although the group is also engaged in several major clinical collaborations. The lab also has a major interest in the regulation of Th1-dependent immunopathology in T. gondii and mycobacterial infections as well as tuberculosis-HIV co-infection.

paradoxical immune reconstitution inflammatory syndrome

X-ray from a pulmonary tuberculosis patient presenting with paradoxical immune reconstitution inflammatory syndrome two weeks after initiation of anti-retroviral therapy.

Credit: NIAID

Biography

Dr. Sher received his Ph.D. from the University of California, San Diego, and did his postdoctoral training in the Division of Parasitology at the National Institute for Medical Research in Mill Hill, London. In 1980, after several years as a research associate and then assistant professor in the department of pathology at Harvard Medical School, he joined NIAID as a section chief in the Laboratory of Parasitic Diseases. Sher became chief of LPD in 2003 and was promoted to NIH Distinguished Investigator in 2011.

Awards

  • Bonazinga Award (Society for Leuckocyte Biology)
  • Bailey K. Ashford Medal (The American Society of Tropical Medicine and Hygiene)
  • U.S. PHS Superior Service Award
  • NIH Director’s Mentoring Award

Memberships

  • Fellow, American Academy of Microbiology
  • Fellow, American Association for the Advancement of Science
  • Brazilian Academy of Sciences

Editorial Boards

  • The Journal of Experimental Medicine (Senior Editor)
  • Faculty of 1000 (Section Head, Immunity to Infections)
  • mBio (American Society of Microbiology Journal)

Research Group

Immunobiology Section Research Group

Immunobiology Section Research Group

Eduardo Amaral, fellow; Takeshi Kawabe, fellow; Nicolas Riteau, fellow; Dragana Jankovic, senior associate scientist; Lara Mittereder, biologist; Ranjani Namasivayam, fellow; Carrie Martin, lab operations coordinator; Preston White, post-bac; Alan Sher, principle investigator; Alice Muglia Thomas da Silva Amancio, fellow (special volunteer); Chiaki Iwamura, fellow; Sara Hieny, biologist; Diego Costa, fellow; Sandy Oland, animal procedure specialist

Selected Publications

Costa DL, Namasivayam S, Amaral EP, Arora K, Chao A, Mittereder LR, Maiga M, Boshoff HI, Barry CE III, Goulding CW, Andrade BB, Sher A.  Pharmacological inhibition of host heme oxygenase-1 suppresses mycobacterium tuberculosis infection in vivo by a mechanism dependent on T lymphocytes. mBio. 2016 Oct 25;7(5):e01675-16.

Kugler DG, Flomerfelt FA, Costa DL, Laky K, Kamenyeva O, Mittelstadt PR, Gress RE, Rosshart SP, Rehermann B, Ashwell JD, Sher A, Jankovic D.  Systemic toxoplasma infection triggers a long-term defect in the generation and function of naïve T lymphocytes. J Exp Med. 2016 Dec. online (doi: 10.1084/jem.20151636).

Tosh KW, Mittereder L, Bonne-Annee S, Hieny S, Nutman TB, Singer SM, Sher A, Jankovic D. The IL-12 response of primary human dendritic cells and monocytes to Toxoplasma gondii is stimulated by phagocytosis of live parasites rather than host cell invasion. J Immunol. 2016 Jan 1;196(1):345-56.

Andrade BB, Pavan Kumar N, Amaral EP, Riteau N, Mayer-Barber KD, Tosh KW. Mainer N, Conceicao EL, Kubler A, Sridhar R, Banurekha VV, Jawahar MS, BarbosaT, Manganiello VC, Moss J, Fontana JR, Marciano BE, Sampaio EP, Oliver KN, Holland KN, Jackson SM, Moayeri M, Leppla S, Sereti I, Barber DL, Ntuman TB, Babu S, Sher A. Heme oxygenase-1 regulation of matrix metalloproteinase-1 expression underlies distinct disease profiles in tuberculosis. J Immunol. 2015 Sep 15;195(6):2763-73.

Mayer-Barber KD, Andrade BB; Oland SD, Amaral EP, Barber DL, Gonzales J, Derrick S, Ruiru S, Nathella Pavan K, Wang W, Xing Y, Guolong Z, Ying C, Subash B, Marta C, Andres SM, Via LE, Barry III CE, Sher A. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature. 2014 Jul 3;511(7507):99-103.

Goldszmid RS, Caspar P, Rivollier A, White S, Dzutsev A, Hieny S, Kelsall B, Trinchieri G, Sher A. NK cell-derived interferon-γ orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infectionImmunity. 2012 Jun 29;36(6):1047-59.

Visit PubMed for a complete publication list.

Accomplishments

  • Demonstration of the role of TLR 11-recognition of parasite profilin in the induction of IL-12 during T. gondii infection
  • Identification of the T2 ribonuclease Omega-1 as the schistosome egg component responsible for conditioning dendritic cells (DC) to trigger Th2 responses
  • Elucidation of endoplasmic reticulum fusion with parasitophorous vacuoles as a mechanism of cross-presentation in T. gondii-infected DC
  • Studies identifying the respective role of toll-like receptors (TLR), IL-1R signaling, and the inflammasome in host resistance to M. tuberculosis and in the adjuvant activity of the mycobacterial component in Complete Freunds Adjuvant
  • Identification of IL-10-producing Th1 cells as major regulators of immunopathology in T. gondii infection
  • Discovery of major roles for the GTPase Irgm1(LRG47) in the regulation of hematopoietic stem development and in interferon (IFN)-dependent autophagic cell death in T lymphocytes
  • First description of in situ cellular dynamics with mycobacterial granulomas in a mammalian host
  • Discovery of role of lipoxins in suppressing cellular response to M. tuberculosis, thereby promoting infection
  • Elucidation of opposing roles of IL-1 and interferons in host resistance to M. tuberculosis and the development of an experimental host directed therapy for TB based on the manipulation of these cytokines with eicosanoids
  • Development of a murine model for studying the pathogenesis of immune reconstitution inflammatory syndrome (IRIS)
  • Discovery of a role of glucocorticoids in the self-regulation of effector CD4+ T-cell function in toxoplasma infection
  • Use of hemoxygenase-1 as a clinical biomarker for active TB and potential target for host directed therapy
Content last reviewed on November 30, 2016