Life Sciences Research for Lifelong Health

Career

Rahul Roychoudhuri studied Clinical Medicine and Natural Sciences at the University of Cambridge. After completing the Clinical Academic Foundation Training Programme in Infectious Diseases at Guy's, King's and St. Thomas' Hospitals and King's College London, Rahul moved to the United States where he undertook a Ph.D. in Dr Gary Nabel's laboratory at the US National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH) studying transcriptional heterogeneity within single immune cells responding to infection.

Rahul undertook a postdoctoral fellowship at Dr Nicholas Restifo's laboratory at the US National Cancer Institute (NCI) where he continued his work on transcriptional regulation within the immune system. A major contribution of this early research was the discovery of mechanisms underlying differentiation of a powerfully suppressive subset of T cells called regulatory T (Treg) cells. I discovered the critical function of the transcription factor BACH2 in Treg lineage specification (Roychoudhuri et al., Nature 2013; Vahedi et al., Nature 2015), and in suppression of immune responses against solid tumours (Roychoudhuri et al., J Clin Invest 2016). This work led to discovery of a new monogenic disease caused by BACH2 insufficiency (Nat Immunol 2017; reviewed in Nat Rev Immunol 2017) and a CRUK-funded industrial collaboration to identify BACH2 inhibitors (Roychoudhuri PI). We showed that Treg differentiation in peripheral tissues is sensitive to local oxygen concentrations resulting in permissivity of the lung to cancer metastasis (Clever, Roychoudhuri, et al., Cell 2016).

My research has also established BACH2 as an intrinsic suppressor of CD8 + T cell activation required for the quiescence and long-term survival of memory cells (Roychoudhuri et al., Nat Immunol, 2016), and AKT inhibition as a means of expanding memory CD8 + T cells for adoptive immunotherapy (Cancer Res 2015). In 2015 Rahul was jointly awarded a Sir Henry Dale Fellowship by the Wellcome Trust and The Royal Society and in 2017 Rahul was awarded a Lister Institute Research Prize.

Our group’s research at the Babraham Institute is focussed on the biology of two cell types with critical functions in tumour immunity: CD4 + Treg cells and cytotoxic CD8 + T cells. CD4 + Treg cells: We have established a programme of research to understand the suppressive mechanisms employed by Treg cells in distinct tissue environments. This has enabled us to uncover and functionally characterise the unique transcriptional programme of tumour-associated Treg cells. We have discovered a novel regulatory circuit controlling Treg-mediated suppression in the gut and have identified a molecular basis for the functional quiescence and survival of resting Treg cells, required for long-term maintenance of Treg responses. We have contributed to studies demonstrating that high potassium levels within the interstitial environment of tumours restricts CD8 + T cell activation (Nature 2016; Science 2019).