Welcome to the Roychoudhuri Lab

Immune regulation in inflammation and cancer

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 that would otherwise cause deleterious inflammation, or immunopathology following infection. 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 infection, inflammation 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.

We are looking for passionate new PhD students, Postdocs, and Master’s students (more info)!

Publication highlights

(For a full list see Publications)

A distal enhancer at risk locus 11q13.5 promotes suppression of colitis by Treg cells

CRISPR-based mutagenesis of disease-associated distal enhancer homologs in mice reveals a regulatory switch for signal-driven GARP expression by Treg cells. The function of the enhancer is required for Treg cells to control gut inflammation.

Nasrallah R, Imianowski C, et al.

[PDF] Nature (2020)

BACH2 promotes the functional quiescence and maintenance of resting Treg cells

The transcription factor BACH2 is repurposed following Treg lineage specification and its high expression in resting Treg cells is required for their quiescence and durable maintenance. Durable maintenance of resting Treg cell responses is required for immune homeostasis and cancer immunosuppression.

Grant FM, Yang J, et al.

[PDF] J Exp Med (2020) in press.

Protocols for integrative genome-wide analysis of transcription factor binding and chromatin accessibility in lymphocytes

Experimental and computational protocols to enable integrative analysis of TF binding and chromatin accessibility in lymphocytes.

Sadiyah MF, Roychoudhuri R.

[PDF] Curr Protoc Immunol (2019) 126:e84.

A human monogenic inflammatory disease caused by loss-of-function mutations in BACH2

The discovery of a human monogenic disease resulting from inactivating mutations of BACH2, termed BACH2-related Immunodeficiency and Autoimmunity (BRIDA). The work, resulted from an international collaboration with clinicians and scientists in the UK and the US.

[PDF] Nat Immunol (2017) 18:813-823.

BACH transcription factors in innate and adaptive immunity

A review on BACH family transcriptional repressors in innate and adaptive immunity. We highlight similarities at a molecular level in the cell-type-specific activities of the BACH factors, proposing that competitive interactions of BACH proteins with transcriptional activators of the bZIP family form a common mechanistic theme underlying their diverse actions.

Igarashi K, Kurosaki T and Roychoudhuri R

[PDF] Nat Rev Immunol (2017) 17:437-450.

High levels of extracellular potassium in tumours suppress T cell activation

Cell death within tumours releases intracellular potassium into the extracellular space causing profound suppression of T cell activation and anti-tumour immunity. Engineering CD8+ T cells to be resistant to high extracellular potassium levels in tumours improves adoptive immunotherapy.

[PDF] Nature (2016) 537:539-543.

Oxygen-sensing by T cells promotes cancer metastasis to the lung

The HIF prolyl hydroxylases PHD1, PHD2 and PHD3 mediate sensitivity of T cells to environmental local oxygen concentrations within tissues, promoting Treg cell differentiation and permissivity of the lung to cancer metastasis.

[PDF] Cell (2016) 166:1117-1131

BACH2 functions as an AP-1 repressor in lymphocytes to promote CD8+ T cell memory

The transcription factor BACH2 functions as a steric repressor of AP-1 transcription factors in CD8+ T cells, restraining TCR-driven terminal effector differentiation to preserve long-lived memory CD8+ T cell responses

[PDF] Nat Immunol (2016) 17:851-860.

Commentary by Sidwell and Kallies (Nat Immunol 17:744-5.

The transcription factor BACH2 promotes tumour immunosuppression through its function in Treg cell development

BACH2 promotes tumour immunosuppression through its role in Foxp3+ Treg cell differentiation. These results are consistent with the results of a recent large in vivo screen of host immunosuppressive factors published by the Adams lab.

[PDF] J Clin Invest (2016) 126:599-604.

The transcriptional repressor BACH2 is required for Treg cell development and suppression of lethal inflammation

The transcription factor BACH2 plays a critical role in Treg cell development, required for immunological tolerance and suppression of lethal inflammation.
Commentary by Kallies and Vasanthakumar (Immunol Cell Biol. 91:491-2.

[PDF] Nature (2013) 498:506-10.

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