Core Faculty

Vijay K. Kuchroo, DVM, PhD

V.K.Director, Evergrande Center for Immunologic Diseases
Samuel L. Wasserstrom Professor of Neurology, Harvard Medical School
Kuchroo Laboratory

Dr. Kuchroo’s laboratory studies focus on the role of pro-inflammatory T cells in inducing tissue inflammation and autoimmune diseases. Dr. Kuchroo's major research interests include autoimmune diseases - particularly the role of co-stimulation - the genetic basis of experimental autoimmune encephalomyelitis and multiple sclerosis, and cell surface molecules and regulatory factors that regulate induction of T cell tolerance and dysfunction. His laboratory has made several animal models, including one for human multiple sclerosis. He was first to describe the development of highly pathogenic Th17 cells, which has been shown to induce multiple different autoimmune diseases in humans. Dr. Kuchroo was also first to describe the inhibitory receptor TIM-3, which is being exploited as a target for cancer immunotherapy. He has published over 325 original research papers in the filed of Immunology and a paper describing development of Th17 authored by Dr. Kuchroo has been one of the highest cited papers in Immunology.

Publications

DUBA-UBR5 axis: other than transactivation.Wu C, Chen Z, Kuchroo VK. Cell Res. 2015 Mar;25(3):273-4. doi: 10.1038/cr.2015.13. Epub 2015 Jan 30. PMID: 25633593; PMC4349248.

A T cell extrinsic mechanism by which IL-2 dampens Th17 differentiation. Anderson AC, Sullivan JM, Tan DJ, Lee DH, Kuchroo VK.  J Autoimmun. 2015 Feb 25. pii: S0896-8411(15)00025-6. doi: 10.1016/j.jaut.2015.02.001. [Epub ahead of print] PMID: 25725581.

Ezh2 lines up the chromatin in T regulatory cells. Wu C, Chen Z, Kuchroo VK.  Immunity. 2015 Feb 17;42(2):201-3. doi: 10.1016/j.immuni.2015.01.019. PMID: 25692693.

Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation. Xiao S, Brooks CR, Sobel RA, Kuchroo VK.  J Immunol. 2015 Feb 15;194(4):1602-8. doi: 10.4049/jimmunol.1402632. Epub 2015 Jan 12. PMID: 25582854; PMC4346345.

An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction. Zhu C, Sakuishi K, Xiao S, Sun Z, Zaghouani S, Gu G, Wang C, Tan DJ, Wu C, Rangachari M, Pertel T, Jin HT, Ahmed R, Anderson AC, Kuchroo VK. Nat Commun. 2015 Jan 23;6:6072. doi: 10.1038/ncomms7072. PMID: 25614966; PMC4311884.

CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, Dougan SK, Petersen BS, Melum E, Pertel T, Clayton KL, Raab M, Chen Q, Beauchemin N, Yazaki PJ, Pyzik M, Ostrowski MA, Glickman JN, Rudd CE, Ploegh HL, Franke A, Petsko GA, Kuchroo VK, Blumberg RS. Nature. 2015 Jan 15;517(7534):386-90. doi: 10.1038/nature13848. Epub 2014 Oct 26. PMID: 25363763; PMC4297519.

Coinhibitory receptors and CD8 T cell exhaustion in chronic infectionsKuchroo VK, Anderson AC, Petrovas C. Curr Opin HIV AIDS. 2014 Sep;9(5):439-45. doi: 10.1097/COH.0000000000000088. PMID: 25010894.

Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells. Wu C, Thalhamer T, Franca RF, Xiao S, Wang C, Hotta C, Zhu C, Hirashima M, Anderson AC, Kuchroo VK. Immunity. 2014 Aug 21;41(2):270-82. doi: 10.1016/j.immuni.2014.06.011. Epub 2014 Jul 24. PMID: 25065622; PMC4219323.

Comment on "Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection". Kuchroo VK, Anderson AC, Freeman GJ. J Immunol. 2014 Jul 15;193(2):467. doi: 10.4049/jimmunol.1401123. PMID: 24994907.

Arlene H. Sharpe, MD, PhD

A.S.Co-Director, Evergrande Center for Immunologics Diseases
George Fabyan Professor of Comparative Pathology, Harvard Medical School
Sharpe Laboratory

Dr. Sharpe’s laboratory investigates T cell costimulatory pathways and their immunoregulatory functions. Her laboratory studies the roles of T cell costimulatory and coinhibitory pathways in regulating immune responses needed for the induction and maintenance of T cell tolerance and effective antimicrobial and antitumor immunity. Dr. Sharpe’s laboratory has discovered T cell costimulatory pathways and elucidated their functions, including the immunoinhibitory functions of the CTLA-4 and PD-1 pathways, which have become exceptionally promising targets for cancer immunotherapy. A major focus of her laboratory is elucidating the role of coinhibitory molecules in mediating tissue tolerance and controlling inflammation. Her laboratory is also involved in studies aimed at translating fundamental understanding of T cell costimulation into new therapies for autoimmune diseases, chronic viral infections, and cancer. Dr. Sharpe has published over 300 papers and was listed by Thomas Reuters as one of the most Highly Cited Researchers (top 1%) in 2014. She was a recipient of the William B. Coley Award for Distinguished Research in Tumor immunology in 2014 for her contributions to the discovery of PD-1 pathway.

Publications

Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stabilityHuynh A, DuPage M, Priyadharshini B, Sage PT, Quiros J, Borges CM, Townamchai N, Gerriets VA, Rathmell JC, Sharpe AH, Bluestone JA, Turka LA. Nat Immunol. 2015 Feb;16(2):188-96. doi: 10.1038/ni.3077. Epub 2015 Jan 5.  PMID:25559257; PMC4297515.

Inducible RNAi in vivo reveals that the transcription factor BATF is required to initiate but not maintain CD8+ T-cell effector differentiation. Godec J, Cowley GS, Barnitz RA, Root DE, Sharpe AH, Haining WN. Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):512-7. doi: 10.1073/pnas.1413291112. Epub 2014 Dec 29. PMID: 25548173; PMC4299213.

The coinhibitory receptor CTLA-4 controls B cell responses by modulating T follicular helper, T follicular regulatory, and T regulatory cells. Sage PT, Paterson AM, Lovitch SB, Sharpe AH. Immunity. 2014 Dec 18;41(6):1026-39. doi: 10.1016/j.immuni.2014.12.005. Epub 2014 Dec 5. PMID: 25526313; PMC4309019.

Circulating T follicular regulatory and helper cells have memory-like propertiesSage PT, Alvarez D, Godec J, von Andrian UH, Sharpe AH.  J Clin Invest. 2014 Dec;124(12):5191-204. doi: 10.1172/JCI76861. Epub 2014 Oct 27. PMID: 25347469; PMC4348955.

Ana C. Anderson, PhD

A.A.Assistant Professor of Neurology, Harvard Medical School
Associate Scientist, Brigham and Women’s Hospital

Dr. Anderson obtained her B.S. in Microbiology and Immunology in 1993 from the University of Miami, where she graduated summa cum laude. She obtained her Ph.D. in Immunology from Harvard University in 1999.  During her Ph.D. she was awarded a fellowship from the Howard Hughes Medical Institute. Dr. Anderson works in the field of cancer immunology, specifically on the role of inhibitory molecules in regulation of the anti-tumor T cell response. Her laboratory identified the inhibitory molecule Tim-3 as a key regulator of T cell dysfunction in cancer. Prior to working in the field of cancer immunology, Dr. Anderson worked in the field of autoimmunity. Dr. Anderson has published over 38 original papers, 12 reviews, and 5 book chapters. Her work on T cell cross-reactivity in autoimmunity was selected by Nature Immunology as a ‘Classic Paper in Autoimmunity’. Dr. Anderson serves on the editorial board for OncoImmunology and Cellular Immunology. She served on the scientific advisory board for CoStim Pharmaceuticals, Inc., which was recently acquired by Novartis and currently serves on the scientific advisory board for Potenza Therapeutics.

Publications

An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction. Zhu C, Sakuishi K, Xiao S, Sun Z, Zaghouani S, Gu G, Wang C, Tan DJ, Wu C, Rangachari M, Pertel T, Jin HT, Ahmed R, Anderson AC*, Kuchroo VK*. Nat Commun. 2015 Jan 23;6:6072. doi: 10.1038/ncomms7072. PMID: 25614966; PMC4311884. *Corresponding authors.

CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, Dougan SK, Petersen BS, Melum E, Pertel T, Clayton KL, Raab M, Chen Q, Beauchemin N, Yazaki PJ, Pyzik M, Ostrowski MA, Glickman JN, Rudd CE, Ploegh HL, Franke A, Petsko GA, Kuchroo VK, Blumberg RS. Nature. 2015 Jan 15;517(7534):386-90. doi: 10.1038/nature13848. Epub 2014 Oct 26. PMID: 25363763; PMC4297519.

Coinhibitory receptors and CD8 T cell exhaustion in chronic infections. Kuchroo VK, Anderson AC, Petrovas C. Curr Opin HIV AIDS. 2014 Sep;9(5):439-45. doi: 10.1097/COH.0000000000000088. PMID: 25010894.

Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells. Wu C, Thalhamer T, Franca RF, Xiao S, Wang C, Hotta C, Zhu C, Hirashima M, Anderson AC, Kuchroo VK. Immunity. 2014 Aug 21;41(2):270-82. doi: 10.1016/j.immuni.2014.06.011. Epub 2014 Jul 24. PMID: 25065622; PMC4219323.

Comment on "Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection". Kuchroo VK, Anderson AC, Freeman GJ. J Immunol. 2014 Jul 15;193(2):467. doi: 10.4049/jimmunol.1401123. PMID: 24994907.

Christophe Benoist, MD, PhD

C.B.Morton Grove-Rasmussen Professor of Immunohematology, Harvard Medical School
Benoist-Mathis Laboratory

The Benoist/Mathis laboratory has studied autoimmunity for over thirty years. The laboratory investigates the genetic, molecular and cellular mechanisms that control immunologic tolerance to self, and how failures of self-tolerance lead to autoimmune/inflammatory diseases such as type-1 diabetes, arthritis or autoimmune polyglandular syndrome. Research addresses central tolerance and the enigmatic factor Aire, and peripheral tolerance via regulatory T cells, their specification and mode of action in preventing autoimmune disease and ensuring orderly responses to commensal microbes. Dr. Benoist has a broad interest in Systems Immunology, and partakes in the Immunoloogical Genome Project. He obtained an M.D. from the Université de Paris, a Ph.D. from the Université Louis Pasteur, Strasbourg, and is a member of the French Académie des Sciences and of the US National Academy of Sciences.

Publications

Noninvasive mapping of pancreatic inflammation in recent-onset type-1 diabetes patients. Gaglia JL, Harisinghani M, Aganj I, Wojtkiewicz GR, Hedgire S, Benoist C, Mathis D, Weissleder R. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2139-44. doi: 10.1073/pnas.1424993112. Epub 2015 Feb 3. PMID: 25650428; PMC4343112.

Population dynamics of islet-infiltrating cells in autoimmune diabetes. Magnuson AM, Thurber GM, Kohler RH, Weissleder R, Mathis D, Benoist C. Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1511-6. doi: 10.1073/pnas.1423769112. Epub 2015 Jan 20. PMID: 25605891; PMC4321317.

Appearance and disappearance of the mRNA signature characteristic of Treg cells in visceral adipose tissue: age, diet, and PPARγ effects. Cipolletta D, Cohen P, Spiegelman BM, Benoist C, Mathis D. Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):482-7. doi: 10.1073/pnas.1423486112. Epub 2014 Dec 30. PMID: 25550516; PMC4299242.

Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells. Fu W, Farache J, Clardy SM, Hattori K, Mander P, Lee K, Rioja I, Weissleder R, Prinjha RK, Benoist C, Mathis D. Elife. 2014 Nov 19;3:e04631. doi: 10.7554/eLife.04631. PMID: 25407682; PMC4270084.

Diane Mathis, PhD

D.M.Morton Grove-Rasmussen Professor of Immunohematology, Harvard Medical School
Benoist-Mathis Laboratory

The Benoist/Mathis laboratory has studied autoimmunity for over thirty years. The laboratory investigates the genetic, molecular and cellular mechanisms that control immunologic tolerance to self, and how failures of self-tolerance lead to autoimmune/inflammatory diseases such as type-1 diabetes, arthritis or autoimmune polyglandular syndrome. More recent interests include the immunology of metabolic diseases and systems immunology. Dr. Mathis obtained her Ph.D. from the University of Rochester. She is a Principal Faculty Member at the Harvard Stem Cell Institute and an Associate Member of the Broad Institute of MIT and Harvard. Dr. Mathis presently serves on Scientific Advisory Boards of the HHMI, Genentech, MedImmune, and Pfizer, Inc. 

Publications

Noninvasive mapping of pancreatic inflammation in recent-onset type-1 diabetes patients. Gaglia JL, Harisinghani M, Aganj I, Wojtkiewicz GR, Hedgire S, Benoist C, Mathis D, Weissleder R. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2139-44. doi: 10.1073/pnas.1424993112. Epub 2015 Feb 3. PMID: 25650428; PMC4343112.

Population dynamics of islet-infiltrating cells in autoimmune diabetes. Magnuson AM, Thurber GM, Kohler RH, Weissleder R, Mathis D, Benoist C. Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1511-6. doi: 10.1073/pnas.1423769112. Epub 2015 Jan 20. PMID: 25605891; PMC4321317.

Appearance and disappearance of the mRNA signature characteristic of Treg cells in visceral adipose tissue: age, diet, and PPARγ effects. Cipolletta D, Cohen P, Spiegelman BM, Benoist C, Mathis D. Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):482-7. doi: 10.1073/pnas.1423486112. Epub 2014 Dec 30. PMID: 25550516; PMC4299242.

Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells. Fu W, Farache J, Clardy SM, Hattori K, Mander P, Lee K, Rioja I, Weissleder R, Prinjha RK, Benoist C, Mathis D. Elife. 2014 Nov 19;3:e04631. doi: 10.7554/eLife.04631. PMID: 25407682; PMC4270084.

Roni Nowarski, PhD

Picture Roni NowarskiAssistant Professor of Neurology, Microbiology and Immunobiology, Harvard Medical School
Associate Scientist, Brigham and Women’s Hospital

Dr. Nowarski’s laboratory studies the innate immune pathways operating within tissues, and the basis for dysregulation of tissue physiology in inflammatory disease. The laboratory investigates the cellular and molecular events that mediate tissue pathology in inflammatory disorders such as colitis, fatty liver disease and sepsis. Dr. Nowarski has identified the inflammatory cytokine IL-18 as the principle driver of the intestinal mucosal dysfunction leading to ulcerative colitis in mice. A major focus of his laboratory is to discover the immunoregulatory factors impacting fundamental tissue functions, to guide the development of therapies aimed at restoring tissue functionality in inflammatory and metabolic disorders. Dr. Nowarski received his PhD in Molecular Biology from the Hebrew University of Jerusalem and completed his postdoctoral studies as a Jane Coffin Childs fellow at Yale University School of Medicine.

Publications

The Stromal Intervention: Regulation of Immunity and Inflammation at the Epithelial-Mesenchymal Barrier. Nowarski, R., R. Jackson, and R. A. Flavell. 2017. Cell 168: 362-375.

Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis. Nowarski, R., R. Jackson, N. Gagliani, M. R. de Zoete, N. W. Palm, W. Bailis, J. S. Low, C. C. Harman, M. Graham, E. Elinav, and R. A. Flavell. 2015. Cell 163: 1444-1456.

NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Wlodarska, M., C. A. Thaiss, R. Nowarski, J. Henao-Mejia, J. P. Zhang, E. M. Brown, G. Frankel, M. Levy, M. N. Katz, W. M. Philbrick, E. Elinav, B. B. Finlay, and R. A. Flavell. 2014. Cell 156: 1045-1059.

Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Elinav, E., R. Nowarski, C. A. Thaiss, B. Hu, C. Jin, and R. A. Flavell. 2013. Nature reviews. Cancer 13: 759-771.

 

Howard L. Weiner, MD

H.W.Robert L. Kroc Professor of Neurology, Harvard Medical School
Co-Director, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital
Weiner Laboratory

Dr. Weiner has had a long-term interest in the immunologic aspects of multiple sclerosis. His laboratory studies the role of inflammation in human CNS autoimmune diseases, including the role of chronic inflammation in multiple sclerosis, Alzheimer’s disease, ALS and brain tumors. As Director and Founder of the Partners Multiple Sclerosis Center, he pioneered the use of immunotherapy and the drug cyclophosphamide for the treatment of multiple sclerosis and has investigated immune abnormalities in the disease including the role of innate immune system and regulatory T cells. Dr. Weiner obtained his doctoral degree from the University of Colorado School of Medicine. He also is a published author and filmmaker.

Publications

MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis. Murugaiyan G, da Cunha AP, Ajay AK, Joller N, Garo LP, Kumaradevan S, Yosef N, Vaidya VS, Weiner HL. J Clin Invest. 2015 Mar 2;125(3):1069-80. doi: 10.1172/JCI74347. Epub 2015 Feb 2.

Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice. Butovsky O, Jedrychowski MP, Cialic R, Krasemann S, Murugaiyan G, Fanek Z, Greco DJ, Wu PM, Doykan CE, Kiner O, Lawson RJ, Frosch MP, Pochet N, Fatimy RE, Krichevsky AM, Gygi SP, Lassmann H, Berry J, Cudkowicz ME, Weiner HL. Ann Neurol. 2015 Jan;77(1):75-99. doi: 10.1002/ana.24304. Epub 2014 Nov 27.

Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Mayo L, Trauger SA, Blain M, Nadeau M, Patel B, Alvarez JI, Mascanfroni ID, Yeste A, Kivisäkk P, Kallas K, Ellezam B, Bakshi R, Prat A, Antel JP, Weiner HL, Quintana FJ. Nat Med. 2014 Oct;20(10):1147-56. doi: 10.1038/nm.3681. Epub 2014 Sep 14.

In vivo anti-LAP mAb enhances IL-17/IFN-γ responses and abrogates anti-CD3-induced oral tolerance. da Cunha AP, Wu HY, Rezende RM, Vandeventer T, Weiner HL. Int Immunol. 2015 Feb;27(2):73-82. doi: 10.1093/intimm/dxu083. Epub 2014 Sep 6.

Differential roles of microglia and monocytes in the inflamed central nervous system. Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM, Cialic R, Wu PM, Doykan CE, Lin J, Cotleur AC, Kidd G, Zorlu MM, Sun N, Hu W, Liu L, Lee JC, Taylor SE, Uehlein L, Dixon D, Gu J, Floruta CM, Zhu M, Charo IF, Weiner HL, Ransohoff RM. J Exp Med. 2014 Jul 28;211(8):1533-49. doi: 10.1084/jem.20132477. Epub 2014 Jul 7.

Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koeglsperger T, Dake B, Wu PM, Doykan CE, Fanek Z, Liu L, Chen Z, Rothstein JD, Ransohoff RM, Gygi SP, Antel JP, Weiner HL. Nat Neurosci. 2014 Jan;17(1):131-43. doi: 10.1038/nn.3599. Epub 2013 Dec 8. Erratum in: Nat Neurosci. 2014 Sep;17(9):1286.