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Dr Rahul Roychoudhuri

Dr Rahul Roychoudhuri

University Senior Lecturer

Research Group Leader

Division of Immunology


Biography:

For a full description of our research, visit: http://roychoudhurilab.org/

Rahul Roychoudhuri is University Senior Lecturer at the University of Cambridge (Pathology), and Fellow and Director of Studies at St. Catharine's College. He studied Natural Sciences at the University of Cambridge and Clinical Medicine at King’s College London. Rahul undertook a Ph.D. in Dr Gary Nabel’s laboratory at the US National Institutes of Health (NIH) and a postdoctoral fellowship at Dr Nicholas Restifo’s laboratory at the US National Cancer Institute (NCI). He has made contributions to our understanding of immune regulation and lymphocyte gene regulation. A major contribution of his early research was the discovery of mechanisms underlying differentiation of a powerfully suppressive subset of T cells called regulatory T (Treg) cells. He discovered the critical function of the transcription factor BACH2 in Treg lineage specification (Roychoudhuri et al., Nature 2013; Vahedi et al., Nature 2015), and in suppression of immune responses against solid tumours (Roychoudhuri et al., J Clin Invest 2016). This work led to discovery of a new monogenic disease caused by BACH2 insufficiency (Nat Immunol 2017; reviewed in Nat Rev Immunol 2017). The laboratory's work has also shown that Treg differentiation in peripheral tissues is sensitive to local oxygen concentrations resulting in permissivity of the lung to cancer metastasis (Clever, Roychoudhuri, et al., Cell 2016). 

Roychoudhuri's work has advanced our understanding of mechanisms that regulate CD8+ T cell memory and function. He established a critical function of BACH2 as a suppressor of CD8+ T cell activation required for the quiescence and long-term survival of memory cells (Roychoudhuri et al., Nat Immunol, 2016), and AKT inhibition as a means of expanding memory CD8+ T cells for adoptive immunotherapy (Cancer Res 2015). The laboratory has contributed to studies demonstrating that high potassium levels within the interstitial environment of tumours restricts CD8+ T cell activation (Nature 2016; Science 2019). Rahul’s research group is focussed on the biology of two cell types with critical functions in inflammation and tumour immunity: CD4+ T cells, including Treg cells, and cytotoxic CD8+ T cells. In 2015 Rahul was jointly awarded a Sir Henry Dale Fellowship by the Wellcome Trust and The Royal Society. In 2017 Rahul was awarded a Lister Institute Research Prize. Rahul is a reviewer for a number of peer-reviewed scientific journals and grant agencies, and serves on the Editorial board of Immunology.

Research themes

Immunology:

Division

Immunology:

Research Interests

Immune regulation in inflammation and cancer

For a full description of our research, visit: http://roychoudhurilab.org/

T cells drive immune activation and promote clearance of infections and cancer. However, their function can also provoke autoimmune and allergic inflammation. The immune system therefore employs a variety of suppressive mechanisms, known as immunoregulatory mechanisms, to restrain excessive T cell activation. Immunoregulatory mechanisms also suppress beneficial anti-tumour T cell responses to drive deleterious immunosuppression in cancer. Immunoregulatory mechanisms therefore function as ‘brakes’ on immune activation and have important consequences in inflammatory diseases and cancer.

Our research aims to uncover the molecular and cellular mechanisms underpinning immunoregulation and cancer immunosuppression. Fundamental discovery in the field of immunoregulation will pave the way for new therapies aimed at manipulating immune function in patients with autoimmunity and cancer.

Our lab utilises cutting-edge molecular immunology, functional genomics and mouse genetics to enable discovery and characterisation of novel host immunoregulatory mechanisms (see Research). We are particularly interested in immunoregulatory mechanisms that control the differentiation and function of CD4+ and CD8+ conventional T cells and Foxp3+ regulatory T (Treg) cells. The lab, led by Dr Rahul Roychoudhuri, is located at the Babraham Institute and the Department of Pathology at the University of Cambridge and works closely with collaborators within both the University and broader Cambridge immunology community. Our science benefits from access to the world-class research facilities of the University of Cambridge and the Babraham Institute.

Key Publications

For a full list of publications see: http://roychoudhurilab.org/publications/

BACH2 drives quiescence and maintenance of resting Treg cells to promote homeostasis and cancer immunosuppression. Grant FM*, Yang J*, Nasrallah R, Clarke J, Sadiyah F, Whiteside SK, Imianowshi CJ, Kuo P,
Vardaka P, Todorov T, Zandhuis N, Patrascan I, Tough D, Kometani K, Eil R, Kurosaki T, Okkenhaug K, Roychoudhuri R (2020). J Exp Med (in Press).

A distal enhancer at risk locus 11q13.5 promotes suppression of colitis by Treg cells. Nasrallah R, Imianowski CJ, Bossini-Castillo L, Grant FM, Dogan M, Placek L, Kozhaya L, Kuo P, Sadiyah F, Whiteside SK, Mumbach MR, Glinos D, Vardaka P, Whyte CE, Lozano T, Fujita T, Fujii H, Liston A, Andrews S, Cozzani A, Yang J, Mitra S, Lugli E, Chang HY, Unutmaz D, Trynka G,
Roychoudhuri R (2020). Nature (in Press).

Phosphoinositide 3-kinase δ inhibition promotes antitumor responses but antagonizes checkpoint inhibitors.
Lim EL, Cugliandolo FM, Rosner DR, Gyori D, Roychoudhuri R, Okkenhaug K
JCI Insight 2018 3 (11). [PDF]

BACH transcription factors in innate and adaptive immunity.
Igarashi K, Kurosaki T, Roychoudhuri R
Nat Rev Immunol 2017 17 (7): 437-450. [PDF]

Ionic immune suppression within the tumour microenvironment limits T cell effector function.
Eil R, Vodnala SK, Clever D, Klebanoff CA, Sukumar M, Pan JH, Palmer DC, Gros A, Yamamoto TN, Patel SJ, Guittard GC, Yu Z, Carbonaro V, Okkenhaug K, Schrump DS, Linehan WM, Roychoudhuri R, Restifo NP
Nature 2016 537 (7621): 539-543. [PDF]

Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche.
Clever D, Roychoudhuri R, Constantinides MG, Askenase MH, Sukumar M, Klebanoff CA, Eil RL, Hickman HD, Yu Z, Pan JH, Palmer DC, Phan AT, Goulding J, Gattinoni L, Goldrath AW, Belkaid Y, Restifo NP
Cell 2016 166 (5): 1117-1131.e14. [PDF]

BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.
Roychoudhuri R, Clever D, Li P, Wakabayashi Y, Quinn KM, Klebanoff CA, Ji Y, Sukumar M, Eil RL, Yu Z, Spolski R, Palmer DC, Pan JH, Patel SJ, Macallan DC, Fabozzi G, Shih HY, Kanno Y, Muto A, Zhu J, Gattinoni L, O'Shea JJ, Okkenhaug K, Igarashi K, Leonard WJ, Restifo NP
Nat Immunol 2016 17 (7): 851-860. [PDF]

The transcription factor BACH2 promotes tumor immunosuppression.
Roychoudhuri R, Eil RL, Clever D, Klebanoff CA, Sukumar M, Grant FM, Yu Z, Mehta G, Liu H, Jin P, Ji Y, Palmer DC, Pan JH, Chichura A, Crompton JG, Patel SJ, Stroncek D, Wang E, Marincola FM, Okkenhaug K, Gattinoni L, Restifo NP
J Clin Invest 2016 126 (2): 599-604. [PDF]

The interplay of effector and regulatory T cells in cancer.
Roychoudhuri R, Eil RL, Restifo NP
Curr Opin Immunol 2015 33 (): 101-11. [PDF]

Type I cytokines synergize with oncogene inhibition to induce tumor growth arrest.
Acquavella N, Clever D, Yu Z, Roelke-Parker M, Palmer DC, Xi L, Pflicke H, Ji Y, Gros A, Hanada K, Goldlust IS, Mehta GU, Klebanoff CA, Crompton JG, Sukumar M, Morrow JJ, Franco Z, Gattinoni L, Liu H, Wang E, Marincola F, Stroncek DF, Lee CC, Raffeld M, Bosenberg MW, Roychoudhuri R, Restifo NP
Cancer Immunol Res 2015 3 (1): 37-47. [PDF]

BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis.
Roychoudhuri R, Hirahara K, Mousavi K, Clever D, Klebanoff CA, Bonelli M, Sciumè G, Zare H, Vahedi G, Dema B, Yu Z, Liu H, Takahashi H, Rao M, Muranski P, Crompton JG, Punkosdy G, Bedognetti D, Wang E, Hoffmann V, Rivera J, Marincola FM, Nakamura A, Sartorelli V, Kanno Y, Gattinoni L, Muto A, Igarashi K, O'Shea JJ, Restifo NP
Nature 2013 498 (7455): 506-10. [PDF]