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Photo of Joe FrostAfter completing his undergraduate degree in Natural Sciences at the University of Cambridge, Joe Frost was awarded joint funding by the RDM Scholars Programme and the Christopher Welch Scholarship in Biological Sciences to conduct a D.Phil., with Professor Hal Drakesmith.

His research in the Drakesmith lab asks how iron availability impacts upon immunity. Genetic defects in immune cell iron uptake have been found to cause a human immunodeficiency syndrome, demonstrating the adaptive immune system's requirement for iron. He hypothesised that iron may become limiting for lymphocytes under conditions of physiological iron deficiency, resulting in an impaired adaptive immune response. Iron deficiency is the most prevalent micronutrient deficiency worldwide; understanding the nutritional requirements of immune responses might help us better implement vaccination regimes.

Using experimental in vivo and in vitro models, h made the discovery that iron availability, controlled by the iron regulatory hormone, hepcidin, critically regulates T cell and B cell responses to vaccination and infection.  This work was published in Med, Cell Press’ new translational medicine journal. These discoveries provide important evidence supporting ongoing investigations testing whether iron supplementation can improve vaccine efficacy. Several trials exploring this concept are underway, and he has contributed to their design.

As well as exploring how altered systemic iron homeostasis alters adaptive immune responses, he also investigated the specific cellular defects of iron-deprived T cells. He found that iron-deprived T cells not only have altered effector functions, but also a defect in their oxidative metabolism, leading us to propose that iron is a novel immunometabolite. These results were built upon by characterising the iron-dependent T cell proteome and the importance of iron for the function of another lymphocyte subset, NK cells, with collaborators in Oxford and Dublin.

After his D.Phil., he stayed in Oxford for a short postdoc position with Professor Drakesmith, investigating the disruption of systemic iron homeostasis in COVID-19 infection, the dependence of innate immunity on iron availability and how modulation of serum iron levels might be exploited therapeutically.

Overall, Dr Frost says that his work has greatly benefited from the facilities and hugely supportive collaborative atmosphere fostered by the Weatherall Institute of Molecular Medicine and RDM. “Without my many colleagues who contributed in a multitude of ways, the progress we made would not have happened”, he said.

He is now looking forward to my next research position as a post-doctoral researcher with Alexander Rudensky at the Sloan Kettering Institute in New York City.