Ethan Shevach, M.D.

Ethan Shevach, M.D.

Chief, Cellular Immunology Section

Major Areas of Research

  • We are studying the role of NK cells and Tregs in the immune system homeostasis in the steady state and disease, especially the role of NKIRs/MHC-I and TCR/MHC-II interactions in viral and tumor immunity.
  • We are investigating mechanisms of Treg mediated suppression. Especially a Treg mediated process similar to trogocytosis to remove peptide MHC-II complexes from dendritic cells (DC) rendering the DC incompetent to present the targeted pMHC-II complex.
  • We are interested in elucidating the function of two members of the Ikaros gene transcription factor (TF) family, Helios and Eos. Both of these TFs are preferentially expressed in Treg and play roles in controlling certain aspects of Treg suppressor functions.
  • We are studying the role of type I interferons (IFNs) in Treg function. We had previously demonstrated that type I IFNs play a role in Treg development and survival.
  • We are working on bringing some of our discoveries from the bench to the clinic by studying hTregs biology by using immunodeficient mice engrafted with human peripheral blood mononuclear cells in collaborations with industry.

Program Description

The major focus of the Cellular Immunology Section over the past 25 years has been furthering our understanding of the function of T regulatory cells (Tregs) that express the transcription factor Foxp3. Our group was one of the first in the world to realize the importance of Treg and we performed many of the initial studies that described their phenotype and function. The study of Tregs is now one of the most active areas of research in basic and clinical immunology and the therapeutic use of Treg is now in the clinic. It was originally assumed that Treg were a dedicated lineage of cells that developed only from thymic precursors, but more recent studies have clearly documented that Foxp3+ T cells also develop from conventional T cells (Tconv) in extra-thymic peripheral sites in vivo, and these are termed peripherally induced Tregs (pTregs). Treg can also be generated in culture in the presence of transforming growth factor-b1 (TGF-b1) and are termed induced Tregs (iTreg). The relative importance of tTreg and pTreg is unknown. Although most of our studies deal with Tregs in mouse models, over the past 15 years we have also carried out studies on human Tregs (hTregs) derived from normal donors. Our ongoing studies are described below and have been divided up into five major projects with significant overlap between the projects. We also intentionally validate new and novel findings that we learn in one species with similar studies in another species, as there appears to be conservation of many aspects of Treg function across the species.

Cell Immunology Fig Image

Two fundamentally different suppressor modes characterize Treg suppressor mechanisms. In the “active” mode, Treg cells secrete immunoinhibitory molecules that exert their effects on other cell types. In contrast, in the “counteractive” mode Treg cells are actively engaged in removing vital components from other cells types including antigen, costimulatory molecules, cytokines, and inflammatory signals thereby decreasing the activation of T effector cells. B. Akkaya and E.M. Shevach, Cellular immunology 2020.

Credit
NIAID

 

Biography

Dr. Shevach received his M.D. from Boston University in 1967. Following clinical training, he joined the Laboratory of Immunology as a senior staff fellow in 1972, was appointed a senior investigator in 1973, and became a section chief in 1987. Dr. Shevach served as editor-in-chief of the Journal of Immunology from 1987 to 1992 and editor-in-chief of Cellular Immunology from 1996 to 2007. Dr. Shevach is the author of more than 450 papers.

Awards

Distinguished Service Award (The American Association of Immunologists)
Distinguished Alumnus Award (Boston University School of Medicine)
2004 William B. Coley Award for Distinguished Research in Basic and Tumor Immunology
Distinguished Scientist Award, World Allergy Congress, 2015
Thompson-Reuters Citation Laureate, 2015
Distinguished Fellow, American Association of Immunologists, 2019

Memberships

The American Association of Immunologists
American Society for Clinical Investigation
Association of American Physicians

Editorial Boards

Immunity
The Journal of Immunological Methods
Journal of Biomedical Science
Journal of Experimental Medicine
Current Protocols in Immunology
Human Immunology

Research Group

Ethan Shevach, M.D., Resarch Group Image

Ethan Shevach, M.D., Resarch Group

Credit
NIAID

Top row, left to right: Yong-Hee Kim, Kirstin Ward, Abir Panda, Nizam Mansoori, Angela Thornton, Suveena Sharma, Pat Korty
Bottom row, left to right: Billur Akkaya, Ethan Shevach, Maja Buszko, Vinay Penna (alumnus), Jafar al Souz (alumnus) Shalini Tanwar
On the top: Melissa Blain, Lyra Morina, Daniel Williams, Kole Tison

Ethan M Shevach, M.D.: Principal Investigator

Angela Thornton, Ph.D., Staff Scientist

Pat Korty, Microbiologist

Suveena Sharma Ph.D., Biologist

Melissa Blain, Biologist

Melissa Blain is a Research Biologist in the Shevach laboratory since 2008. She has a M.S in Medical Biology with a concentration in Hematology and Immunology, and a B.S in Biochemical Pharmacology.

Billur Akkaya Ph.D., Research fellow

Billur received her medical degree at Hacettepe University, Turkey and obtained her PhD from University of Oxford, UK. Her research in Shevach lab revealed a novel mechanism by which regulatory T cells perform antigen-specific suppression. She received 2019 Sidney & Joan Pestka Post Graduate Award for Excellence in Cytokine and Interferon Research, 2019 American Association of Immunology Thermo Fisher Trainee Achievement Award and 2018 NIH Fellows Award for Research Excellence.

Shalini Tanwar Ph.D., Visiting Postdoctoral fellow

Shalini completed her PhD from National Institute of Immunology under the guidance of Dr. Rath where she worked on cross talk between T and B lymphocytes during developmental. Here for her postdoctoral work, she has been working on the cross talk between regulatory T cells (Treg) and MDSCs during autoimmunity. Besides she is also involved in deciphering the role of Eos in Treg development, differentiation and function

Abir Panda Ph.D., Visiting Postdoctoral fellow

Abir received his Ph.D. in Biotechnology in 2016 from Bose Institute, India where he worked in the lab of Prof. Gaurisankar Sa & Prof. Tanya Das (Division of Molecular Medicine). Abir is currently studying the critical roles of NK and Treg cells in maintaining immune homeostasis in the steady state and in augmentation of anti-viral (acute and chronic) and anti-tumor immunity.

Maja Buszko Ph.D., Visiting Postdoctoral fellow

Maja received her Ph.D. in Medical Science in 2016 from the Medical University of Innsbruck, Austria. Her work is focused on targeting hTregs for the enhancement of anti-tumor immunity. In 2019/2020 Maja has been a part of the NIH/FDA Immunology Interest Group Steering Committee. She received the 2020 NIH Fellows Award for Research Excellence.

Yong-Hee Kim M.D. Ph.D., Visiting Postdoctoral fellow

Yong-Hee received his PhD in immunology in 2013 from Seoul National University College of Medicine, South Korea where he worked in Chung-Gyu Park’s lab. Currently he is studying pTreg induction and transplantation tolerance.

Mohammad Nizam Mansoori Ph.D., Visiting Postdoctoral fellow 

Nizam has received his PhD in the area of osteoimmunology from Council of Scientific and Industrial Research – Central Drug Research Institute (CSIR-CDRI), India in 2017. He joined NIH as a Visiting Scientist in 2017. Currently, he is studying the mechanism of antigen specific CD8 T cell regulation by iTregs both in vitro and in vivo. In 2020, he got AAI Trainee abstract award.

Lyra Morina B.S., Post-baccalaureate Fellow

Lyra received a B.S. in Cell Biology & Molecular Genetics and B.S. in Economics at the University of Maryland College Park where she completed her undergraduate thesis in Megan Fritz’s lab. Her current project is focused on characterizing the activation of regulatory T cells in humanized mice. She hopes to pursue her interest in cancer immunology as a future physician-scientist.

Kole Tison, B.S., Post-baccalaureate Fellow

Kole is interested in the immunological function of regulatory T cells and their implications in disease. He studies the role of an ikaros family transcription factor (Helios) in conventional T cells. Kole has a Bachelor of Science from Montana State University in Cell Biology and Neuroscience.

Daniel Williams, B.S., Post-baccalaureate Fellow

Dan is conducting work examining the role of the transcription factor Tbet in Treg survival and function during type 1 inflammation. Prior to joining the Shevach lab, he earned a BA in Biochemistry from Bowdoin College in Brunswick Maine.

Selected Publications

Tanwar S, Oguz C, Metidji A, Dahlstrom E, Barbian K, Kanakabandi K, Sykora L, Shevach EM. Type I IFN signaling in T regulatory cells modulates chemokine production and myeloid derived suppressor cells trafficking during EAE. J Autoimmun. 2020 Jul 21;102525. Epub ahead of print.

Panda AK, Gangaplara A, Buszko M, Natarajan K, Boyd LF, Sharma S, Margulies DH, Shevach EM. Cutting Edge: Inhibition of the Interaction of NK Inhibitory Receptors with MHC Class I Augments Antiviral and Antitumor Immunity. J Immunol. 2020 Aug 1;205(3):567-572.

Lopez-Ocasio M, Buszko M, Blain M, Wang K, Shevach EM. T Follicular Regulatory Cell Suppression of T Follicular Helper Cell Function Is Context-Dependent in vitro. Front Immunol. 2020 Apr 17;11:637.

Gokhale AS, Gangaplara A, Lopez-Occasio M, Thornton AM, Shevach EM. Selective deletion of Eos (Ikzf4) in T-regulatory cells leads to loss of suppressive function and development of systemic autoimmunity. J Autoimmun. 2019 Dec;105:102300.

Skadow M, Penna VR, Galant-Swafford J, Shevach EM, Thornton AM. Helios Deficiency Predisposes the Differentiation of CD4+Foxp3- T Cells into Peripherally Derived Regulatory T Cells. J Immunol. 2019 Jul 15;203(2):370-378.

Akkaya B, Oya Y, Akkaya M, Al Souz J, Holstein AH, Kamenyeva O, Kabat J, Matsumura R, Dorward DW, Glass DD, Shevach EM. Regulatory T cells mediate specific suppression by depleting peptide-MHC class II from dendritic cells. Nat Immunol. 2019 Feb;20(2):218-231.

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