skip to primary navigationskip to content
 

Dr Rahul Roychoudhuri

Research Interests

T cells regulate immune function by differentiating into highly specialised cellular lineages that either drive or constrain immune reactions. Consequently, T cells play pervasive roles in health and disease. Whereas effector T cells promote clearance of infections and cancer, regulatory T cells suppress their function to limit excessive immune activation. However, the suppressive function of regulatory T cells can also prevent effective immune responses against chronic infections and cancer. Thus, mechanisms that control T cell differentiation are attractive targets in the development of new therapies for a broad range of disorders.
 
The focus of the group is to understand how a class of proteins, called transcription factors, regulate cell fate-specification and function within the T cell lineage. Transcription factors play key roles in driving cellular identity and bind to regulatory elements within the genome to control its structure and function. We use a broad range of approaches in cellular immunology, mouse genetics, protein biochemistry, molecular biology, and functional genomics to resolve mechanisms by which transcription factors regulate immune function in the context of homeostasis, infection and cancer. 

Rahul will start at the Babraham institute shortly and is recruiting post-doc and PhD positions, and applicants should (currently) email the following email address: rahul.roychoudhuri@babraham.ac.uk

Keywords

FOXP3 ; epigenetics ; BACH2 ; T cells ; phosphorylation ; regulatory T cells ; CD4 ; lymphocytes, ; signalling ; tumour immunology ; CD8 ; mouse immunology ; gene regulation ; cancer immunology

Key Publications

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 Invest2016 doi: 10.1172/JCI82884.
 
Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy.
Sukumar M, Liu J, Mehta GU, Patel SJ, Roychoudhuri R, Crompton JG, Klebanoff CA, Ji Y, Li P, Yu Z, Whitehill GD, Clever D, Eil RL, Palmer DC, Mitra S, Rao M, Keyvanfar K, Schrump DS, Wang E, Marincola FM, Gattinoni L, Leonard WJ, Muranski P, Finkel T, Restifo NP.  
Cell Metab. 2015 Ahead of print.
 
Memory T cell-driven differentiation of naive cells impairs adoptive immunotherapy.
Klebanoff CA, Scott CD, Leonardi AJ, Yamamoto TN, Cruz AC, Ouyang C, Ramaswamy M,Roychoudhuri R, Ji Y, Eil RL, Sukumar M, Crompton JG, Palmer DC, Borman ZA, Clever D, Thomas SK, Patel S, Yu Z, Muranski P, Liu H, Wang E, Marincola FM, Gros A, Gattinoni L, Rosenberg SA, Siegel RM, Restifo NP.  
J Clin Invest. 2015 Ahead of print.
 
Oncogenic PI3Kα promotes multipotency in breast epithelial cells.
Okkenhaug K, Roychoudhuri R.  
Sci Signal. 2015 8:3.
 
Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.
Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, Ji Y, Van Panhuys N, Klebanoff CA, Sukumar M, Clever D, Chichura A, Roychoudhuri R, Varma R, Wang E, Gattinoni L, Marincola FM, Balagopalan L, Samelson LE, Restifo NP.  
J Exp Med. 2015 212:2095-113.
 
Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection.
Omilusik KD, Best JA, Yu B, Goossens S, Weidemann A, Nguyen JV, Seuntjens E, Stryjewska A, Zweier C, Roychoudhuri R, Gattinoni L, Bird LM, Higashi Y, Kondoh H, Huylebroeck D, Haigh J, Goldrath AW.  
J Exp Med. 2015 212:2027-39. 

Nutrient Competition: A New Axis of Tumor Immunosuppression.
Sukumar M, Roychoudhuri R, Restifo NP.  
Cell. 2015 162:1206-8.

The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells.
Khor B, Gagnon JD, Goel G, Roche MI, Conway KL, Tran K, Aldrich LN, Sundberg TB, Paterson AM, Mordecai S, Dombkowski D, Schirmer M, Tan PH, Bhan AK, Roychoudhuri R, Restifo NP, O'Shea JJ, Medoff BD, Shamji AF, Schreiber SL, Sharpe AH, Shaw SY, Xavier RJ.  
Elife. 2015 22;4. 
 
Lineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape.
Crompton JG, Narayanan M, Cuddapah S, Roychoudhuri R, Ji Y, Yang W, Patel SJ, Sukumar M, Palmer DC, Peng W, Wang E, Marincola FM, Klebanoff CA, Zhao K, Tsang JS, Gattinoni L, Restifo NP.  
Cell Mol Immunol. 2015 [Epub ahead of print]
 
The interplay of effector and regulatory T cells in cancer.
Roychoudhuri R, Eil RL, Restifo NP.  
Curr Opin Immunol. 2015 33:101-11.
 
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.   

miR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines.
Ji Y, Wrzesinski C, Yu Z, Hu J, Gautam S, Hawk NV, Telford WG, Palmer DC, Franco Z, Sukumar M, Roychoudhuri R, Clever D, Klebanoff CA, Surh CD, Waldmann TA, Restifo NP, Gattinoni L.  
PNAS. 2015 112:476-81.
 
Transcriptional profiles reveal a stepwise developmental program of memory CD8(+) T cell differentiation.
Roychoudhuri R, Lefebvre F, Honda M, Pan L, Ji Y, Klebanoff CA, Nichols CN, Fourati S, Hegazy AN, Goulet JP, Gattinoni L, Nabel GJ, Gilliet M, Cameron M, Restifo NP, Sékaly RP, Flatz L.  
Vaccine. 2015 33:914-23.
 
Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics.
Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, Tran E, Hanada K, Yu Z, Palmer DC, Kerkar SP, Michalek RD, Upham T, Leonardi A, Acquavella N, Wang E, Marincola FM, Gattinoni L, Muranski P, Sundrud MS, Klebanoff CA, Rosenberg SA, Fearon DT, Restifo NP.  
Cancer Res. 2015 75:296-305.
 
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 3:37-47.

 

Roychoudhuri R, Lefebvre F, Honda M, Pan L, Ji Y, Klebanoff CA, Nichols C, Fourati S, Hegazy AN, Goulet JP, Gattinoni L, Nabel GJ, Gilliet M, Cameron M, Restifo NP, Sékaly RP, Flatz L. The transcriptional program of vaccine-induced CD8+ T cell memory.
Vaccine. 2014 Nov 1. pii: S0264-410X(14)01367-X

Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil R, Tran E, Hanada KI, Yu Z, Palmer DC, Kerkar SP, Michalek RD, Upham T, Leonardi A, Aquavella N, Wang E, Marincola FM, Gattinoni L, Muranski P, Sundrud MS, Klebanoff CA, Rosenberg SA, Fearon DT, Restifo NP. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res. 2014 Nov 28. pii: canres.2277.2014. [Epub ahead of print]

Acquavella N, Clever D, Yu Z, Roelke-Parker M, Palmer DC, Xi L, Pflicke H, Ji Y, Gros A, Hanada KI, 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. Type I Cytokines Synergize with Oncogene Inhibition to Induce Tumor Growth Arrest. Cancer Immunol Res. 2014 Oct 30. [Epub ahead of print]

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. BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis. Nature. 2013 Jun 27;498(7455):506-10.

Sukumar M, Liu J, Ji Y, Subramanian M, Crompton JG, Yu Z, Roychoudhuri R, Palmer DC, Muranski P, Karoly ED, Mohney RP, Klebanoff CA, Lal A, Finkel T, Restifo NP, Gattinoni L. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function. J Clin Invest. 2013 Oct 1;123(10):4479-88. 

Klebanoff CA, Spencer SP, Torabi-Parizi P, Grainger JR, Roychoudhuri R, Ji Y, Sukumar M, Muranski P, Scott CD, Hall JA, Ferreyra GA, Leonardi AJ, Borman ZA, Wang J, Palmer DC, Wilhelm C, Cai R, Sun J, Napoli JL, Danner RL, Gattinoni L, Belkaid Y, Restifo NP. Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. J Exp Med. 2013 Sep 23;210(10):1961-76. 

Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, Sukumar M, Reger RN, Yu Z, Kern SJ, Roychoudhuri R, Ferreyra GA, Shen W, Durum SK, Feigenbaum L, Palmer DC, Antony PA, Chan CC, Laurence A, Danner RL, Gattinoni L, Restifo NP. Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity. 2011 Dec 23;35(6):972-85. 

Flatz L, Cheng C, Wang L, Foulds KE, Ko SY, Kong WP, Roychoudhuri R, Shi W, Bao S, Todd JP, Asmal M, Shen L, Donaldson M, Schmidt SD, Gall JG, Pinschewer DD, Letvin NL, Rao S, Mascola JR, Roederer M, Nabel GJ. Gene-based vaccination with a mismatched envelope protects against simian immunodeficiency virus infection in nonhuman primates. J Virol. 2012;86(15): 7760-70.

Flatz L, Roychoudhuri R, Honda M, Filali-Mouhim A, Goulet JP, Kettaf N, Lin M, Roederer M, Haddad EK, Sékaly RP, Nabel GJ. Single-cell gene-expression profiling reveals qualitatively distinct CD8 T cells elicited by different gene-based vaccines.
Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5724-9. doi: 10.1073/pnas.1013084108. Epub 2011 Mar 21.