Biography
Bidesh Mahata obtained his PhD in Biochemistry from the University of Calcutta, India, in 2008. In 2009, he moved to the University of Dundee, UK, for his postdoctoral research with Dr Dimitris Xirodimas. In 2011, he joined Teichmann Laboratory, MRC-Laboratory of Molecular Biology, Cambridge, UK, as an investigator scientist. There he discovered that T helper 2 lymphocytes upregulate Cyp11a1 expression, the enzyme that catalyses the first and rate-limiting step of steroid biosynthesis, and produce steroid hormones, possibly to resolve immune reactions and restore homeostasis. Fascinated by that discovery, he went on to develop discovery tools to study immune cell-mediated steroidogenesis. In 2013, the Teichmann Laboratory moved to the EMBL-EBI and Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. There he took initiatives to generate a novel Cyp11a1-mCherry reporter mouse line to track steroidogenic cells and a conditional knockout mouse line to ablate steroidogenesis cell type specifically. Using these discovery tools and with outstanding support from the Teichmann Laboratory (particularly in the area of single-cell genomics), he discovered that tumour infiltrating T cells, mast cells and basophils are steroidogenic and these steroidogenic immune cells are involved in anti-tumour immunosuppression. In 2019, he joined the Department of Pathology, University of Cambridge, UK, to lead a research team focussed on immune cell steroidogenesis.
Research
We discovered that immune cells can synthesise and secrete steroid hormones to regulate their own function. At present we know very little about the physiological and pathological role of this immune cell-mediated steroid biosynthesis. Therefore, we are curious to know the cause, mechanism and consequence of this immune cell-mediated steroid biosynthesis, and committed to exploiting that knowledge to improve human health and combat disease.
Our initial studies suggest that immune cell-mediated steroid biosynthesis is involved in type-2 immune responses such as helminth infection, allergies and allergic asthma, pregnancy and many solid tumours. We hypothesise (1) immune cell-mediated steroid biosynthesis is required to resolve immune response and restore tissue homeostasis in helminth infections, (2) this regulatory process is mutated in allergies and allergic asthma, and (3) in solid tumours it is associated with anti-tumour immunosuppression and immune evasion. We prioritised to study the role of steroidogenic immune cells in regulating anti-tumour immunity, and aim to develop a novel immunotherapeutic strategy against cancer. We undertake multidisciplinary approaches to answer our questions of why, how and when immune cells produce steroids.
Publications
1. Mahata B*, Pramanik J, van der Weyden L, Kar G, Riedel A, Fonseca NA, Kundu K, Ryder E, Duddy G, Walczak I, Davidson S, Okkenhaug K, Adams DJ, Shields JD* and Teichmann SA* (2018) Tumors induce de novo steroid biosynthesis in T cells to evade immunity. Biorxiv, doi: https://doi.org/10.1101/471359
2. Pramanik J, Chen X, Kar G, Henriksson J, Gomes T, Park J, Natarajan K, Meyer KB, Miao Z, McKenzie AN, Mahata B*, and Teichmann SA* (2018) Genome-wide analyses reveal the IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation. Genome Medicine 10:76
3. Mahata B*, Zhang X, Kolodziejczyk AA, Proserpio V, Haim-Vilmovsky L, Taylor AE, Hebenstreit D, Dingler FA, Moignard V, Göttgens B, Arlt W, McKenzie AN, Teichmann SA*. (2014) Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis. Cell Rep 7: 1130-1142.
