Vijay Kuchroo

Vijay K. Kuchroo is an Indian-American immunologist and serial entrepreneur.[1][2][3][4] He is the Samuel L. Wasserstrom chair of Neurology at Harvard Medical School, and Brigham and Women's Hospital. He is also the director of the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts.

Vijay Kuchroo
Born
Baramulla, J&K, India
NationalityIndian - American
CitizenshipUnited States of America
Alma mater
  • Haryana Agricultural University
  • University of Queensland
  • National Institutes of Health, Bethesda
  • Harvard Medical School
Occupation(s)Immunologist, Entrepreneur
Years active1992–present

Prof. Kuchroo specializes in autoimmunity, neuroscience, and cancer immunotherapy. He is best known for discovering the co-inhibitory molecule TIM-3, the TIM family of genes, and the subset of immune cells called Th17 cells. He is also a member of the Broad Institute in Cambridge, Massachusetts, and senior scientist at the Brigham and Women's Hospital.

Career

He was awarded a Ph.D. in veterinary pathology from the University of Queensland in 1985 [5] Subsequently he was a Fogarty International Fellow at NIH for a year before becoming a research fellow at the department of pathology at Harvard Medical School. He later joined the faculty of the Center for Neurologic Diseases at Brigham and Women’s Hospital as a junior faculty member.[5]

In 2004, Dr. Kuchroo was promoted to Professor of Neurology at Harvard Medical School and senior scientist at Brigham and Women's Hospital. In 2005, he was awarded an endowed personal chair from Biogen.[6] He served as co-director for the Center for Infection and Immunity at the Brigham Research Institutes and Brigham and Women's Hospital. In 2014, Dr. Kuchroo founded the Evergrande Center[7] for Immunologic Diseases and currently serves as its founding director. Evergrande Center is a joint center between Harvard Medical School and Brigham and Women's Hospital, dedicated to studying the molecular and genetic basis of tissue inflammation in multiple human diseases, including cancer and autoimmune diseases.[8]

Kuchroo raised funding from external sources to start a teaching course in India called Winter School in Immunology in India.[9]

Kuchroo serves or has served on the editorial boards of several peer-reviewed scientific journal, including Journal of Experimental Medicine, Journal of Immunology, Journal of Neuroimmunology, International Immunology, Cellular Immunology, Scandinavian Journal of Immunology, and Autoimmunity. He also serves or has served on the scientific review boards for Howard Hughes Medical Institute, National Multiple Sclerosis Society, Juvenile Diabetes Research Foundation, and NIH Panel of Elite Reviewers. Dr. Kuchroo is also on the board of directors and scientific advisory boards of multiple biotech and pharmaceutical companies.[10]

Research

Kuchroo initial contribution to the field began with using genetic approaches of transgenesis to generate mouse models for human disease Multiple Sclerosis,[11] a key tool for MS research the world over. He then discovered a novel, cell-surface molecule on T cells called TIM-3,[12] a co-inhibitory molecule, along with the rest 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 both autoimmunity and cancer. 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, AML, and MDS.[13][14][15]

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.[13]

Kuchroo's most critical contribution to the field has come from his discovery of a novel IL-17 cytokine-producing T cell subset, Th17 cells.[16][17] His was the first group to report the identity of this subset in 2005, together with other investigators in the field, followed by identification of pathways for their differentiation in 2006.[18][19][20][21] The Kuchroo lab conducted extensive studies characterizing their role in autoimmune disease pathogenesis, and together with Aviv Regev[22][23] at the Broad Institute, built the regulatory network for the development. 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, which has now been confirmed by multiple epidemiological studies.[24][25][26][27]

Kuchroo has published over 400 peer-reviewed, original articles, and one of his papers is one of the highest-cited papers in the field of Immunology.[28] Many of his groundbreaking discoveries - most notably TIM-3 and Th17 cells - have developed into therapies for patients, with several active clinical trials based on his research[13][29] and 6 pharmaceutical companies founded, based on his discoveries.[30][31][32][33]

Awards

References
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  5. "Vijay K. Kuchroo". Broad Institute. 3 April 2013. Retrieved 23 March 2022.
  6. "Principal Investigator – Kuchroo Laboratory". Retrieved 28 January 2021.
  7. "Harvard announces Evergrande support of three initiatives". Harvard Gazette. 2 December 2013. Retrieved 28 January 2021.
  8. "About". evergrande.hms.harvard.edu. Retrieved 28 January 2021.
  9. "5th Winter School of Immunology, 2012". Retrieved 28 January 2021.
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  12. Monney, Laurent; Sabatos, Catherine A.; Gaglia, Jason L.; Ryu, Akemi; Waldner, Hanspeter; Chernova, Tatyana; Manning, Stephen; Greenfield, Edward A.; Coyle, Anthony J.; Sobel, Raymond A.; Freeman, Gordon J.; Kuchroo, Vijay K. (31 January 2002). "Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease". Nature. 415 (6871): 536–541. doi:10.1038/415536a. PMID 11823861. S2CID 4403803. Retrieved 28 January 2021.
  13. Borate, Uma; Esteve, Jordi; Porkka, Kimmo; Knapper, Steve; Vey, Norbert; Scholl, Sebastian; Garcia-Manero, Guillermo; Wermke, Martin; Janssen, Jeroen; Traer, Elie; Chua, Chong Chyn; Narayan, Rupa; Tovar, Natalia; Kontro, Mika; Ottmann, Oliver; Sun, Haiying; Longmire, Tyler; Szpakowski, Sebastian; Liao, Serena; Patel, Anuradha; Rinne, Mikael L.; Brunner, Andrew; Wei, Andrew H. (13 November 2019). "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. 134: 570. doi:10.1182/blood-2019-128178. Retrieved 28 January 2021.
  14. Qin, Shuang; Xu, Linping; Yi, Ming; Yu, Shengnan; Wu, Kongming; Luo, Suxia (6 November 2019). "Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4". Molecular Cancer. 18 (1): 155. doi:10.1186/s12943-019-1091-2. PMC 6833286. PMID 31690319.
  15. Das, Madhumita; Zhu, Chen; Kuchroo, Vijay K. (2017). "Tim-3 and its role in regulating anti-tumor immunity". Immunological Reviews. 276 (1): 97–111. doi:10.1111/imr.12520. PMC 5512889. PMID 28258697.
  16. Bettelli, Estelle; Carrier, Yijun; Gao, Wenda; Korn, Thomas; Strom, Terry B.; Oukka, Mohamed; Weiner, Howard L.; Kuchroo, Vijay K. (11 May 2006). "Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells". Nature. 441 (7090): 235–238. Bibcode:2006Natur.441..235B. doi:10.1038/nature04753. PMID 16648838. S2CID 4391497. Retrieved 28 January 2021.
  17. Bettelli, Estelle; Kuchroo, Vijay K. (17 January 2005). "IL-12- and IL-23-induced T helper cell subsets: birds of the same feather flock together". The Journal of Experimental Medicine. 201 (2): 169–171. doi:10.1084/jem.20042279. PMC 2212800. PMID 15657286.
  18. Langrish, Claire L.; Chen, Yi; Blumenschein, Wendy M.; Mattson, Jeanine; Basham, Beth; Sedgwick, Jonathan D.; McClanahan, Terrill; Kastelein, Robert A.; Cua, Daniel J. (17 January 2005). "IL-23 drives a pathogenic T cell population that induces autoimmune inflammation". The Journal of Experimental Medicine. 201 (2): 233–240. doi:10.1084/jem.20041257. PMC 2212798. PMID 15657292.
  19. Park, Heon; Li, Zhaoxia; Yang, Xuexian O.; Chang, Seon Hee; Nurieva, Roza; Wang, Yi-Hong; Wang, Ying; Hood, Leroy; Zhu, Zhou; Tian, Qiang; Dong, Chen (November 2005). "A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17". Nature Immunology. 6 (11): 1133–1141. doi:10.1038/ni1261. PMC 1618871. PMID 16200068.
  20. Harrington, Laurie E.; Hatton, Robin D.; Mangan, Paul R.; Turner, Henrietta; Murphy, Theresa L.; Murphy, Kenneth M.; Weaver, Casey T. (November 2005). "Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages". Nature Immunology. 6 (11): 1123–1132. doi:10.1038/ni1254. PMID 16200070. S2CID 11717696. Retrieved 28 January 2021.
  21. Bettelli, Estelle; Carrier, Yijun; Gao, Wenda; Korn, Thomas; Strom, Terry B.; Oukka, Mohamed; Weiner, Howard L.; Kuchroo, Vijay K. (11 May 2006). "Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells". Nature. 441 (7090): 235–238. Bibcode:2006Natur.441..235B. doi:10.1038/nature04753. PMID 16648838. S2CID 4391497. Retrieved 28 January 2021.
  22. Yosef, Nir; Shalek, Alex K.; Gaublomme, Jellert T.; Jin, Hulin; Lee, Youjin; Awasthi, Amit; Wu, Chuan; Karwacz, Katarzyna; Xiao, Sheng; Jorgolli, Marsela; Gennert, David; Satija, Rahul; Shakya, Arvind; Lu, Diana Y.; Trombetta, John J.; Pillai, Meenu R.; Ratcliffe, Peter J.; Coleman, Mathew L.; Bix, Mark; Tantin, Dean; Park, Hongkun; Kuchroo, Vijay K.; Regev, Aviv (25 April 2013). "Dynamic regulatory network controlling TH17 cell differentiation". Nature. 496 (7446): 461–468. Bibcode:2013Natur.496..461Y. doi:10.1038/nature11981. PMC 3637864. PMID 23467089.
  23. Patel, Dhavalkumar D.; Kuchroo, Vijay K. (15 December 2015). "Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions". Immunity. 43 (6): 1040–1051. doi:10.1016/j.immuni.2015.12.003. PMID 26682981.
  24. Wu, Chuan; Yosef, Nir; Thalhamer, Theresa; Zhu, Chen; Xiao, Sheng; Kishi, Yasuhiro; Regev, Aviv; Kuchroo, Vijay K. (25 April 2013). "Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1". Nature. 496 (7446): 513–517. Bibcode:2013Natur.496..513W. doi:10.1038/nature11984. PMC 3637879. PMID 23467085.
  25. Jiang, Xia; Sundström, Björn; Alfredsson, Lars; Klareskog, Lars; Rantapää-Dahlqvist, Solbritt; Bengtsson, Camilla (May 2016). "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". Annals of the Rheumatic Diseases. 75 (5): 943–946. doi:10.1136/annrheumdis-2015-209009. PMID 26903441. S2CID 39553062. Retrieved 28 January 2021.
  26. O'Shea, John J.; Jones, Russell G. (25 April 2013). "Autoimmunity: Rubbing salt in the wound". Nature. 496 (7446): 437–439. Bibcode:2013Natur.496..437O. doi:10.1038/nature11959. PMID 23467087. S2CID 38702589.
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Authored bibliography
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