906-Kaplan, Mark
Faculty

Mark H. Kaplan, PhD

Chair, Department of Microbiology & Immunology

Address
Microbiology/Immunology
635 Barnhill Drive, MS 420

Indianapolis, IN 46202

Bio

Professor Kaplan received an Honours B.Sc. from the University of Windsor in 1987 (Biology) and a PhD. from Wayne State University in 1992 (Immunology and Microbiology). He did postdoctoral work at the University of Texas Southwestern Medical Center and at the Harvard University School of Public Health. He joined the Faculty in the Indiana University School of Medicine in 1998 as an Assistant Professor of Microbiology and Immunology. In 2005, he moved to the Department of Pediatrics to become the Director of Pediatric Pulmonary Basic Research. In 2008, he was promoted to Professor and in 2014 was honored with the Billie Lou Wood Professorship. In 2017, Dr. Kaplan was named as Associate Director of the HB Wells Center for Pediatric Research. In 2020 Dr. Kaplan became the Chair of the Department of Microbiology and Immunology and the Director of Basic Sciences for the Brown Center for Immunotherapy. He was also named the Nicole Brown Professor of Immunology

Much of Professor Kaplan’s work has focused on understanding the function of transcription factors in the development of T helper cell subsets. He has a long standing interest in Signal Transducer and Activator of Transcription or STAT proteins that are activated downstream of cytokines. His more recent work has made great progress towards understanding the development and function of IL-9-secreting T cells in the development of allergic inflammation. Ongoing interests lie in understanding how T cell subsets contribute to allergic and autoimmune inflammation. Developing projects include the contribution of IL-9 signaling to allergic inflammation and to the tumor microenvironment.

Professor Kaplan has been on the Editorial Boards of the Journal of Immunology and JAK-STAT and is currently the Editor-In-Chief for the new American Association of Immunologists journal ImmunoHorizons. He has served on and chaired numerous study sections for grant application to the National Institutes of Health, and other private and international review panels. He has served on the IUSM Biomedical Research Committee for over ten years and is currently the co-chair. He is also the Director of the NIH-funded T32 Training Program in Immunology and Infectious Diseases.

 

Key Publications

Chang HC, Sehra S, Goswami R, Yao W, Yu Q, Stritesky GL, Jabeen R, Han L, Nguyen ET, McKinley CD, Tepper RS, Robertson MJ, Perumal NB, Nutt SL and Kaplan MH. (2010) The transcription factor PU.1 is required for the development of IL-9-secreting T cells and allergic inflammation. Nature Immunology. 11:527-534. PMC3136246.

Jabeen R, Goswami R, Awe O, Kulkarni A, Nguyen ET, Attenasio A, Walsh D, Olson MR, Kim MH, Tepper RS, Sun J, Kim CH, Taparowsky EJ, Zhou B and Kaplan MH. (2013). Th9 cell development requires a BATF-regulated transcriptional network. Journal of Clinical Investigation. 123(11):4641–4653. PMC3809790.

Sehra S, Yao W, Nguyen ET, Glosson-Byers NL, Akhtar N, Zhou B, and Kaplan MH. (2015). Th9 cells are required for tissue mast cell accumulation during allergic inflammation. J Allergy Clin Immunol. 136(2):433-440.e1. PMC4530056

Serezani APM, Bozdogan G, Sehra S, Walsh D, Krishnamurthy P, Potchanant EAS, Nalepa G, Goenka S, Turner MJ, Spandau DF, Kaplan MH. (2017) IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. J. Allergy Clin Immunol. 139(1):142-151.e5. PMC5222746    

Koh B, Abdul Qayum A, Srivastava R, Fu Y, Ulrich BJ, Janga SC, Kaplan MH. 2018. A conserved enhancer regulates Il9 expression in multiple lineages. Nat. Commun. 9:4803.  PMC6237898

Deak PE, Kim B, Abdul Qayum A, Shin J, Vitalpur G, Kloepfer KM, Turner MJ, Smith N, Shreffler WG, Kiziltepe T, Kaplan MH and Bilgicer B. (2019). Designer Covalent Heterobivalent Inhibitors Prevent IgE-Dependent Responses to Peanut Allergen. Proc. Natl. Acad. Sci.-USA. 116:8966-8974. PMC6500160

 Koh B, Ulrich BJ, Nelson AS, Panangipalli G, Kharwadkar R, Wu W, Xie MM, Fu Y, Turner MJ, Paczesny S, Janga SC, Dent AL, and Kaplan MH (2020) Bcl6 and Blimp1 reciprocally regulate ST2+ Treg cell development in the context of allergic airway inflammation. J All Clin Immunol. 146(5):1121-1136.e9. PMCID: PMC7487006

Park S, Griesenauer B, Jiang H, Adom J, Mehrpouya-Bahrami P, Chakravorty S, Kazemian M, Srivastava R, Hayes TA, Pardo J, Janga SC, Paczesny S, Kaplan MH and Olson MR. (2020) Granzyme A producing T helper cells are critical for acute grant-versus-host disease. JCI Insight. 5(18):124465. (Co-corresponding/senior author) PMCID: PMC7526544

 
Fu Y, Wang J, Panangipalli G, Ulrich BJ, Koh B, Xu C, Kharwadkar R, Chu X, Wang Y, Gao H, Wu W, Sun J, Tepper RS, Zhou B, Janga SC, Yang K, Kaplan MH. (2020) STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus. Nat. Comm. 11(1):4882.  PMC7523001

Mehrpouya-Bahrami P, Moriarty A, de Melo P, Keeter WC, Alakhras N, Nelson AS, Hoover M, Barrios M, Nadler JL, Serezani H, Kaplan MH, Galkina EV. (2021) STAT4 is expressed in neutrophils and promotes antimicrobial immunity. JCI Insight. In press. (Co-corresponding/senior author)

Titles & Appointments

  • Chair, Department of Microbiology & Immunology
  • Director of Basic Science, Brown Center for Immunotherapy
  • Nicole Brown Professor of Immunology
  • Professor of Microbiology & Immunology
  • Professor of Pediatrics
  • Adjunct Professor of Biochemistry & Molecular Biology
  • Education
    1997 FEL Harvard University School of Public Health
    1995 FEL University of Texas Southwestern Medical Center
    1992 PhD Wayne State University
    1987 BSC University of Windsor
  • Research

    The overall focus of my laboratory over more than 20 years has been on understanding the transcriptional regulation of T helper cells as they regulate inflammatory immunity. This line of research began when as a postdoctoral fellow we generated STAT4- and STAT6-deficient mice. The early years of my laboratory’s work continued the characterization of STAT4 and STAT6 function, working at multiple levels, from examining gene regulatory mechanisms and chromatin modifications, to defining how factors control cellular function and inflammatory disease in mouse model system, to finally trying to take observations to using human and patient samples to demonstrate the link between basic research and human immune-mediated health and disease.

    My laboratory’s multi-level approach, performing hard-core studies on transcription factor-dependent gene regulation, defining transcription factor-mediated changes in cell function in vitro and in vivo, and ultimately showing conservation in human samples and where possible, linkage to human disease, continues to be a strength in our studies.

    STAT proteins in regulation of inflammation
    Over the past two decades we have made considerable progress in understanding how STAT proteins regulate the development of T helper subsets. More recently, we have focused on defining the function of STAT4 in non-T cells and we are exploring roles of STAT4 in anti-bacterial immunity and autoimmunity.

    Almost two decades ago we developed a mouse model transgenic for a constitutively active STAT6 in T cells. These mice are predisposed towards spontaneous allergic inflammation, particularly in the skin. We have characterized the pathogenesis of skin inflammation and ongoing work is examining changes in the skin responses following injury.  

    IL-9 immunobiology
    Among the most recent subsets of T cells described, Th cells that are primed for production of IL-9 still have functions that are underappreciated. As we have focused on these cells in the last decade we have defined regulatory elements in the Il9 gene, defined transcription factors that contribute to regulation of IL-9 and defined functions of mast cells including control of mast cell homeostasis in mucosal tissues during allergic inflammation. Current projects are exploring control of mast cells in more mechanistic depth.

    In chronic airway inflammation we have defined a resident memory population of T cells that secrete IL-9. In a memory model, these IL-9 secreting T cells are critical for the development of recall responses to allergen. Within this model, we have defined IL-9 responding cells including structural cells in the airways, macrophages, B cells, and innate lymphoid cells. Ongoing work is exploring the generation and maintenance of these cells and further exploring the IL-9 targets that contribute to allergic memory responses. 

    In defining the function of IL-9 beyond mast cells we have identified macrophages as important targets for IL-9-stimulated biology in multiple contexts. IL-9 responsiveness in macrophages is critical for the development of allergic inflammation. Moreover, macrophages are required for the pro-tumorigenic activity of IL-9 in the growth of lung tumors. Ongoing work will define IL-9-dependent macrophage functions that contribute to these immune environments.

    Allergic disease
    We have developed numerous collaborations to explore other aspects of allergic disease. We collaborate with the Dent lab on regulation of the IgE response in vivo, examining the relative roles of Th2, Tfh, and Tfr cells in generating high affinity IgE antibodies. We are collaborating with the Cook-Mills lab in examining neonatal models of atopic dermatitis. Finally, we are collaborating with Basar Bilgicer, a biochemical engineer at University of Notre Dame who has developed novel reagents that inhibit allergen-stimulated IgE responses. We have established efficacy in a humanized mouse model and are working towards testing the inhibitor in patient populations.

  • Professional Organizations
    American Academy of Allergy, Asthma, and Immunology
    American Association for the Advancement of Science
    American Association of Immunologists
    International Cytokine Society (ICS)
  • Awards
    Org: IU School of Medicine
    Desc: IUSM Faculty Mentoring Award
    Scope: School
    Date:
    Org:
    Desc: Billie Lou Wood Endowed Chair
    Scope: University
    Date:

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