Vijay Kuchroo

Last updated

Vijay K. Kuchroo
Born
Baramulla, J&K, India
NationalityIndian - American
Citizenship United States of America
Alma mater
  • Haryana Agricultural University
  • University of Queensland
  • National Institutes of Health, Bethesda
  • Harvard Medical School
Occupation(s)Immunologist, Entrepreneur

Vijay K. Kuchroo is an Indian-American immunologist and entrepreneur. [1] He is the Samuel L. Wasserstrom Professor of Neurology at Harvard Medical School and Brigham & Women's Hospital [2] , and the founding Director of The Gene Lay Institute of Immunology and Inflammation at Brigham & Women's Hospital, Massachusetts General Hospital, and Harvard Medical School in Boston, Massachusetts. [3] He is also a member of the Broad Institute in Cambridge, Massachusetts. [4]

Contents

Kuchroo is known for his research in autoimmunity, neuroimmunology, and cancer immunology. Seminal work from the Kuchroo laboratory include discovery of the co-inhibitory receptor TIM-3, and other TIM family of genes [5] , and a pathogenic immune cell subset that drives autoimmune neuroinflammation called Th17 cells. [6]

Career

Kuchroo graduated with honors from a Bachelor of Veterinary Science from Haryana Agricultural University, Hisar, India, and obtained a Ph.D. in Veterinary Pathology from the University of Queensland, Brisbance Australia. [4] He then completed postdoctoral training in the United States, first at the National Institutes of Health (NIH) as a Fogarty International Fellow and subsequently as a Research Fellow in the Department of Pathology at Harvard Medical School, where he went on to join the faculty. [7] Kuchroo later joined Harvard Medical School’s Neurology Department as a junior faculty member, and was promoted in 2004 to Professor, and Senior Scientist at Brigham & Women's Hospital. [8] . In 2005, he was named the first incumbent of the Samuel L. Wasserstrom chair of Neurology, an endowed chair established with a gift to Harvard Medical School from Boston Biotechnology company, Biogen, and named in honor of Howard Weiner’s grandfather who was killed in the Holocaust. In 2014, Kuchroo became founding Director of the Evergrande Center for Immunologic Diseases, [4] a joint center between Harvard Medical School and Brigham & Women's Hospital dedicated to studying the molecular and genetic basis of tissue inflammation in human diseases [9] . In 2023, he was appointed as the inaugural Director of The Gene Lay Institute of Immunology and Inflammation], which was established with a $100 million gift to Brigham & Women's Hospital from biotechnology entrepreneur and founder of Biolegend, Gene Lay, MS, DVM. [3]

Kuchroo is on the board of directors and scientific advisory boards of multiple biotech and pharmaceutical companies. [10] [11] [1]

Research

Kuchroo's earlier work established myelin proteolipid protein – a major protein of the central nervous system (CNS) – as a bona fide self-antigen that induces neuroinflammation [12] [13] To study autoimmune inflammation in the CNS, his laboratory has generated transgenic mice models which spontaneously develop neuroinflammation, [14] including the 2D2 transgenic mice which are now widely used to study CNS autoimmunity. [15]

The immune checkpoint receptor, T-cell immunoglobulin and mucin-domain containing-3 (TIM-3, encoded by the Havcr2 gene), along with other members of the TIM family of genes, was first cloned by Kuchroo and his team. [5] , along with other members of the TIM family of genes. He was the first to characterize the inhibitory function of TIM-3 and its role in inhibiting T cell responses in autoimmunity and cancer [16] . Similar to other checkpoint inhibitors such as PD-1 and CTLA-4, TIM-3 has been successfully targeted to treat several solid and hematogenous malignancies, including melanoma, Acute Myeloid Leukemia, and myelodysplastic syndrome. [17] [18] [19] Kuchroo was instrumental in shepherding anti-Tim-3 antibody from discovery through to clinic by working with a number of biotech and drug companies to its ultimate use by Novartis for treatment in cancer. [17]

Kuchroo's most critical contribution to the field of immunology has come from his discovery in 2005 of a novel IL-17 cytokine-producing T cell subset – Th17 cells – that drives autoimmune inflammation. [6] This pivotal discovery by his and other research groups [20] [21] [22] at the time was followed by the identification of pathways that regulate their differentiation and pro-inflammatory functions. The Kuchroo lab extensively characterized the role of Th17 cells in autoimmune disease pathogenesis, and together with bioinformatician Aviv Regev at the Broad Institute, built the regulatory network for the development. [23] [24] [25] Dr. Kuchroo was instrumental in promoting clinical trials of IL-17-blockade for the treatment of autoimmune diseases. He was also the first to identify a link between high salt and generation of Th17 cells, suggesting a role of high salt diets in triggering autoimmune diseases, [26] [27] which has now been confirmed by multiple epidemiological studies. [28] [29]

Kuchroo has published over 430 peer-reviewed, original articles [30] , and his paper reporting the development of Th17 cells [6] is one of the highest-cited papers in the field of Immunology. [31] Many of his groundbreaking discoveries - most notably around TIM-3 and Th17 cells - are being developed for clinical therapies, with several active clinical trials based on his research [17] [32] and several pharmaceutical companies founded, based on these discoveries. [33] [34] [35] [36]

Awards

References

  1. 1 2 https://www.cataliocapital.com/team/vijay-k-kuchroo
  2. ↑ https://dms.hms.harvard.edu/people/vijay-kumar-kuchroo
  3. 1 2 https://www.bostonglobe.com/2023/05/09/metro/brigham-creates-institute-focused-immunology-with-record-100-million-gift/
  4. 1 2 3 4 5 https://www.broadinstitute.org/bios/vijay-k-kuchroo
  5. 1 2 Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, Manning S, Greenfield EA, Coyle AJ, Sobel RA, Freeman GJ, Kuchroo VK. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002 Jan 31;415(6871):536-41. doi: 10.1038/415536a. PMID: 11823861.
  6. 1 2 3 Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006 May 11;441(7090):235-8. doi: 10.1038/nature04753. Epub 2006 Apr 30. PMID: 16648838.
  7. ↑ https://kuchroolab.bwh.harvard.edu/principal-investigator/
  8. 1 2 https://cytokinesociety.org/2020/04/30/sarah-gaffen-and-vijay-kuchroo-are-jointly-recognized-for-the-2020-icis-biolegend-william-e-paul-award-for-their-combined-contributions-deciphering-the-role-of-a-key-cytokine-il-17-in-health-and-dise/
  9. ↑ https://news.harvard.edu/gazette/story/2013/12/harvard-announces-evergrande-support-of-three-initiatives/
  10. ↑ https://www.bioconbiologics.com/about-us/board-of-directors/vijay-kuchroo-biocon/
  11. ↑ https://www.bicara.com/team/vijay-kuchroo-d-v-m-ph-d/
  12. ↑ Greer JM, Sobel RA, Sette A, Southwood S, Lees MB, Kuchroo VK. Immunogenic and encephalitogenic epitope clusters of myelin proteolipid protein. J Immunol. 1996 Jan 1;156(1):371-9. PMID: 8598487.
  13. ↑ Markovic-Plese S, Fukaura H, Zhang J, al-Sabbagh A, Southwood S, Sette A, Kuchroo VK, Hafler DA. T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans. J Immunol. 1995 Jul 15;155(2):982-92. PMID: 7541828.
  14. ↑ Waldner H, Whitters MJ, Sobel RA, Collins M, Kuchroo VK. Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3412-7. doi: 10.1073/pnas.97.7.3412. PMID: 10737797; PMCID: PMC16253.
  15. ↑ Bettelli E, Pagany M, Weiner HL, Linington C, Sobel RA, Kuchroo VK. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J Exp Med. 2003 May 5;197(9):1073-81. doi: 10.1084/jem.20021603. PMID: 12732654; PMCID: PMC2193967.
  16. ↑ Sabatos CA, Chakravarti S, Cha E, Schubart A, Sánchez-Fueyo A, Zheng XX, Coyle AJ, Strom TB, Freeman GJ, Kuchroo VK. Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol. 2003 Nov;4(11):1102-10. doi: 10.1038/ni988. Epub 2003 Oct 12. PMID: 14556006.
  17. 1 2 3 Uma Borate, Jordi Esteve, Kimmo Porkka, Steve Knapper, Norbert Vey, Sebastian Scholl, Guillermo Garcia-Manero, Martin Wermke, Jeroen Janssen, Elie Traer, Chong Chyn Chua, Rupa Narayan, Natalia Tovar, Mika Kontro, Oliver Ottmann, Haiying Sun, Tyler Longmire, Sebastian Szpakowski, Serena Liao, Anuradha Patel, Mikael L Rinne, Andrew Brunner, Andrew H. Wei; Phase Ib Study of the Anti-TIM-3 Antibody MBG453 in Combination with Decitabine in Patients with High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). Blood 2019; 134 (Supplement_1): 570. doi: https://doi.org/10.1182/blood-2019-128178
  18. ↑ Qin, S., Xu, L., Yi, M. et al. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4. Mol Cancer 18, 155 (2019). https://doi.org/10.1186/s12943-019-1091-2
  19. ↑ Das M, Zhu C, Kuchroo VK. Tim-3 and its role in regulating anti-tumor immunity. Immunol Rev. 2017 Mar;276(1):97-111. doi: 10.1111/imr.12520. PMID: 28258697; PMCID: PMC5512889.
  20. ↑ Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005 Jan 17;201(2):233-40. doi: 10.1084/jem.20041257. PMID: 15657292; PMCID: PMC2212798.
  21. ↑ Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005 Nov;6(11):1133-41. doi: 10.1038/ni1261. Epub 2005 Oct 2. PMID: 16200068; PMCID: PMC1618871.
  22. ↑ Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005 Nov;6(11):1123-32. doi: 10.1038/ni1254. Epub 2005 Oct 2. PMID: 16200070.
  23. ↑ Yosef N, Shalek AK, Gaublomme JT, Jin H, Lee Y, Awasthi A, Wu C, Karwacz K, Xiao S, Jorgolli M, Gennert D, Satija R, Shakya A, Lu DY, Trombetta JJ, Pillai MR, Ratcliffe PJ, Coleman ML, Bix M, Tantin D, Park H, Kuchroo VK, Regev A. Dynamic regulatory network controlling TH17 cell differentiation. Nature. 2013 Apr 25;496(7446):461-8. doi: 10.1038/nature11981. Epub 2013 Mar 6. PMID: 23467089; PMCID: PMC3637864.
  24. ↑ Schnell A, Huang L, Singer M, Singaraju A, Barilla RM, Regan BML, Bollhagen A, Thakore PI, Dionne D, Delorey TM, Pawlak M, Meyer Zu Horste G, Rozenblatt-Rosen O, Irizarry RA, Regev A, Kuchroo VK. Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity. Cell. 2021 Dec 22;184(26):6281-6298.e23. doi: 10.1016/j.cell.2021.11.018. Epub 2021 Dec 6. PMID: 34875227; PMCID: PMC8900676.
  25. ↑ Patel DD, Kuchroo VK. Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions. Immunity. 2015 Dec 15;43(6):1040-51. doi: 10.1016/j.immuni.2015.12.003. PMID: 26682981.
  26. ↑ Wu, C., Yosef, N., Thalhamer, T. et al. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 496, 513–517 (2013). https://doi.org/10.1038/nature11984
  27. ↑ {Jiang X, Sundström B, Alfredsson L, Klareskog L, Rantapää-Dahlqvist S, Bengtsson C. High sodium chloride consumption enhances the effects of smoking but does not interact with SGK1 polymorphisms in the development of ACPA-positive status in patients with RA. Ann Rheum Dis. 2016 May;75(5):943-6. doi: 10.1136/annrheumdis-2015-209009. Epub 2016 Feb 22. PMID: 26903441.
  28. ↑ Jiang X, Sundström B, Alfredsson L, Klareskog L, Rantapää-Dahlqvist S, Bengtsson C. High sodium chloride consumption enhances the effects of smoking but does not interact with SGK1 polymorphisms in the development of ACPA-positive status in patients with RA. Ann Rheum Dis. 2016 May;75(5):943-6. doi: 10.1136/annrheumdis-2015-209009. Epub 2016 Feb 22. PMID: 26903441.
  29. ↑ {Sigaux J, Semerano L, Favre G, Bessis N, Boissier MC. Salt, inflammatory joint disease, and autoimmunity. Joint Bone Spine. 2018 Jul;85(4):411-416. doi: 10.1016/j.jbspin.2017.06.003. Epub 2017 Jun 23. PMID: 28652101.
  30. ↑ https://www.ncbi.nlm.nih.gov/sites/myncbi/vijay.kuchroo.1/bibliography/40374104/public/?sort=date&direction=ascending
  31. ↑ "Google Scholar". scholar.google.com. Retrieved 28 January 2021.
  32. ↑ Acharya N, Sabatos-Peyton C, Anderson AC. Tim-3 finds its place in the cancer immunotherapy landscape. J Immunother Cancer. 2020 Jun;8(1):e000911. doi: 10.1136/jitc-2020-000911. PMID: 32601081; PMCID: PMC7326247.
  33. ↑ "gsk" (PDF). Retrieved 28 January 2021.
  34. ↑ "Leadership | Board or Directors | Investors | Tizona Therapeutics". www.tizonatx.com. Retrieved 28 January 2021.
  35. ↑ "potenzatherapeutics" . Retrieved 28 January 2021.
  36. ↑ "Novartis inks deal to buy CoStim, a Cambridge biotech that focuses on oncology". Boston Business Journal. Retrieved 28 January 2021.
  37. ↑ https://www.aai.org/Awards/Career/AAI-Meritorious-Career-Award
  38. ↑ https://www.nationalmssociety.org/news-and-magazine/news/dystel-prize-professor-vojay-kuchroo
  39. ↑ https://www.aai.org/Awards/Career/Distinguished-Fellows-of-AAI/Past-Recipients
  40. ↑ https://www.lupusresearch.org/2018-distinguished-innovator-awardees-named-lupus-research-alliance/
  41. ↑ https://www.nobelprizemedicine.org/kuchroo/
  42. 1 2 3 https://www.isniweb.org/congress/profile/vijay-kuchroo/
  43. ↑ https://hria.org/impact-stories/king/

Authored bibliography

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.