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Randall Johnson Project

Supervisor:   Randall Johnson

 

Role of hypoxic response in immunotherapy 

We have investigated how T cells utilise hypoxic response to allow immune response.  We are actively investigating this in terms of models of immunological response to cancer; and we are also asking how myeloid/lymphoid interactions are affected by the response to oxygenation. The project will employ specific hypoxia-induced molecules, particularly metabolites related to hypoxic response, and determine how they can be employed to improve immunotherapeutic responses such as epigenetic changes leading to immune cell persistence in vivo.

Relevant references:

1.  Sim J, Cowburn AS, Palazon A, Madhu B, Tyrakis PA, Macias D, Bargiela DM, Pietsch S, Gralla M, Evans CE, Kittipassorn T, Chey YCJ, Branco CM, Rundqvist H, Peet DJ, and Johnson RS. (2018) The Factor Inhibiting HIF aspariginyl hydroxylase regulates oxidative metabolism and accelerates metabolic adaptation to hypoxia. Cell Metabolism 27:898-913

2.  Palazon A, Tyrakis PA, Macias D, Veliça P, Rundqvist H, Fitzpatrick S, Vojnovic N, Phan AT, Loman N, Hedenfalk I, Hatschek T, Lövrot J, Foukakis T, Goldrath AW, Bergh J, and Johnson RS. (2017) A HIF-1a/VEGF-A axis in cytotoxic T cells regulates tumor progression. Cancer Cell 32(5):669–683

3.  Tyrakis P, Palazon A, Macias D,  Kian LL, Phan AT, Veliça P, You J, Chia GS, Sim J, Doedens A, Abelanet A, Evans CE, Griffiths JR, Poellinger L, Goldrath AW and Johnson RS. (2016) S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate.  Nature 540:236-241