Life Sciences Research for Lifelong Health

Lymphocytes


Rahul Roychoudhuri

Mechanisms of tolerance and immunosuppression

CD4+ and CD8+ effector T cells promote immune activation and drive clearance of infections and cancer but their function is restricted by a diverse set of peripheral tolerance mechanisms. While such mechanisms are required to prevent deleterious autoimmune and allergic reactions, they also powerfully suppress immune responses against chronic infections and cancer, preventing immune-mediated rejection of disease.

Our research aims to understand molecular and cellular mechanisms of peripheral tolerance and immunosuppression, using a variety of approaches including mouse genetics, cellular and molecular immunology, functional genomics and protein biochemistry. Targeting mechanisms underlying peripheral tolerance and immunosuppression may enable development of new therapies aimed at manipulating immune function in patients with inflammation and cancer.


Key publications

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.

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.

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.


Joining the group

Informal enquiries regarding PhD and postdoctoral positions can be made by email and should include details of the applicant's research background and a curriculum vitae.
 
Email Rahul
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Keywords

differentiation
gene expression
immunity
inflammation
regulation
t cell
transcription

Group Members

Latest Publications

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

Memory T cell-driven differentiation of naive cells impairs adoptive immunotherapy.

Klebanoff CA, Scott CD, Leonardi AJ

The Journal of clinical investigation
1558-8238: (2015)

PMID: 26657860

Oncogenic PI3Kα promotes multipotency in breast epithelial cells.

Okkenhaug K, Roychoudhuri R

Science signaling
8 1937-9145:pe3 (2015)

PMID: 26535006

Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape.

Crompton JG, Narayanan M, Cuddapah S

Cellular & molecular immunology
2042-0226: (2015)

PMID: 25914936