Life Sciences Research for Lifelong Health

f5c0168a75ad6e3fc07695b678743fb4.jpg

Rahul Roychoudhuri

Transcriptional regulation of T cell differentiation

T cells coordinate immune function by differentiating into highly specialised cellular lineages. Whereas effector CD4+ and CD8+ T cells promote immune activation and drive clearance of infections and cancer, CD4+ regulatory T (Treg) cells, dependent upon the transcription factor Foxp3, suppress their function, preventing excessive autoimmune and allergic reactions. The suppressive function of Treg cells also powerfully prevents immune responses against cancer. 
 
 
Effector cells and regulatory T cells arise from common precursors yet establish dichotomous function. How is this dichotomous functional programme established and maintained?​

We are interested in understanding general principles and specific mechanisms by which the process of gene expression is controlled within T cells. We hope to apply this knowledge to better understand how the function of the immune system is regulated under physiological conditions, and how the immune system can be manipulated in autoimmunity, infections and cancer. The laboratory employs a variety of techniques including mouse genetics, cellular and molecular immunology, functional genomics and protein biochemistry.


Key publications

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.

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 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.

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.
 
We are currently accepting applications for the following PhD studentships in the lab: 
 PhD studentship 
Understanding molecular mechanisms of CD4+ T cell differentiation
Supervisor(s): Dr R Rahul Roychoudhuri
Application Deadline: January 2017
 

Group Members

Latest Publications

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

The interplay of effector and regulatory T cells in cancer.

Roychoudhuri R, Eil RL, Restifo NP

Current opinion in immunology
33C 1879-0372:101-111 (2015)

PMID: 25728990

Super-enhancers delineate disease-associated regulatory nodes in T cells.

Vahedi G, Kanno Y, Furumoto Y

Nature
1476-4687: (2015)

PMID: 25686607