Life Sciences Research for Lifelong Health


Roychoudhuri Lab

Molecular mechanisms of tolerance and immunosuppression

CD4+ and CD8+ effector T cells promote immune activation and can drive clearance of infections and cancer. Effector T cells can also promote autoimmune and allergic inflammation, a potentially deleterious activity which is restrained by a diverse set of peripheral tolerance mechanisms. While mechanisms of peripheral tolerance therefore play a beneficial role in preventing inflammation, they can also powerfully suppress immune responses during chronic infections and cancer in a process known as immunosuppression.

Our research aims to understand molecular and cellular mechanisms of peripheral tolerance and immunosuppression under physiological conditions, and during infection, inflammation and cancer using a variety of approaches including mouse genetics, cellular immunology, molecular biology and functional genomics. Identifying mechanisms of peripheral tolerance and immunosuppression may enable development of new therapies aimed at manipulating immune function in patients with inflammation and cancer.


Joining the group

Applications are currently sought for two postdoctoral research scientist positions in the laboratory (closing date for applications is 03/05/2018). Click the following links for details: 

Postdoctoral Research Scientist in Lymphocyte Gene Regulation 

Postdoctoral Research Scientist in Tumour Immunity and Immunosuppression

Informal enquiries may be made by those wishing to make studentship or fellowship applications to undertake PhD and postdoctoral research in the group. These can be made by email and should include details of the applicant's research background and a curriculum vitae. 


Key publications

For a full list of publications, click here
 

BACH transcription factors in innate and adaptive immunity. 
Igarashi K, Kurosaki T, Roychoudhuri R.
Nat Rev Immunol  2017 doi: 10.1038/nri.2017.26. 

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, Marston Linehan W, Roychoudhuri R, Restifo NP.
Nature  2016 doi:10.1038/nature19364

Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche
David Clever, Rahul Roychoudhuri, Michael G. Constantinides, Michael H. Askenase, Madhusudhanan Sukumar, Christopher A. Klebanoff, Robert L. Eil, Heather D. Hickman, Zhiya Yu, Jenny H. Pan, Douglas C. Palmer, Anthony T. Phan, John Goulding, Luca Gattinoni, Ananda W. Goldrath, Yasmine Belkaid, Nicholas P. Restifo.
Cell  2016 166:1117-31.

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 17:851-60.

The transcription factor BACH2 promotes tumor immunosuppression. 
Roychoudhuri R, Eil RL, Clever D, Klebanoff CA, Sukumar M, Grant F, 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 126:599-604.

Super-enhancers delineate disease-associated regulatory nodes in T cells.
Vahedi G, Kanno Y, Furumoto Y, Jiang K, Parker SC, Erdos MR, Davis SR, Roychoudhuri R, Restifo NP, Gadina M, Tang Z, Ruan Y, Collins FS, Sartorelli V, O'Shea JJ. 
Nature  2015 520:558-62.


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 498:506-10.

Group Members

Latest Publications

Bach2 Promotes B Cell Receptor-Induced Proliferation of B Lymphocytes and Represses Cyclin-Dependent Kinase Inhibitors.

Miura Y, Morooka M, Sax N

Journal of immunology (Baltimore, Md. : 1950)
1550-6606: (2018)

PMID: 29540581

Epigenetic control of CD8+ T cell differentiation.

Henning AN, Roychoudhuri R, Restifo NP

Nature reviews. Immunology
1474-1741: (2018)

PMID: 29379213

BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.

Afzali B, Grönholm J, Vandrovcova J

Nature immunology
1529-2916: (2017)

PMID: 28530713

BACH transcription factors in innate and adaptive immunity.

Igarashi K, Kurosaki T, Roychoudhuri R

Nature reviews. Immunology
1474-1741: (2017)

PMID: 28461702

Ionic immune suppression within the tumour microenvironment limits T cell effector function.

Eil R, Vodnala SK, Clever D

Nature
537 1476-4687:539-543 (2016)

PMID: 27626381

Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche.

Clever D, Roychoudhuri R, Constantinides MG

Cell
166 1097-4172:1117-1131.e14 (2016)

PMID: 27565342

BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.

Roychoudhuri R, Clever D, Li P

Nature immunology
1529-2916: (2016)

PMID: 27158840

The transcription factor BACH2 promotes tumor immunosuppression.

Roychoudhuri R, Eil RL, Clever D

The Journal of clinical investigation
1558-8238: (2016)

PMID: 26731475

Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy.

Sukumar M, Liu J, Mehta GU

Cell metabolism
1932-7420: (2015)

PMID: 26674251