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.
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.
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.
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.