Selected publications

• Prentice A M, Doherty C P, Abrams S A, Cox S E, Atkinson S H, Verhoef H, Armitage A E, and Drakesmith H (2012) Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children. Blood.

• Armitage Andrew E, Eddowes Lucy A, Gileadi Uzi, Cole Suzanne, Spottiswoode Natasha, Selvakumar Tharini A, Ho Ling-Pei, Townsend Alain RM, and Drakesmith Hal (2011) Hepcidin regulation by innate immune and infectious stimuli. Blood, 118(15):4129-39.

• Portugal Silvia, Carret Celine, Recker Mario, Armitage Andrew E, Goncalves Ligia A, Epiphanio Sabrina, Sullivan David, Roy Cindy, Newbold Chris I, Drakesmith Hal, and Mota Maria M (2011) Host-mediated regulation of superinfection in malaria. Nat Med, 17(6):732-7.

• Drakesmith Hal and Prentice Andrew (2008) Viral infection and iron metabolism. Nat Rev Microbiol, 6(7):541-52.

Dr Hal Drakesmith

Almost all forms of life require iron to thrive.   Iron plays essential biochemical roles in oxygen binding, ATP synthesis and DNA metabolism.  During infection, pathogens need to acquire iron from their human host.  If iron availability is high, infections can progress more rapidly.  On the other hand, inflammatory mechanisms deny iron to invading microbes, slowing the growth of microbes, and giving immune responses more time to act.  Pathogens may become resistant to antibiotics, and can mutate to avoid recognition by the immune system, but they cannot escape the basic metabolic requirement for iron.  We are investigating the battle for this key nutrient and hope to develop a new strategy to combat infections based around manipulating iron transport.

The human peptide hormone hepcidin is the master controller of iron metabolism; too little hepcidin leads to iron overload, too much causes anaemia.  We are defining how hepcidin is modulated during infection and inflammation, and assessing whether deliberately altering hepcidin can control experimental infections of iron-requiring pathogens.  We are also studying hepcidin regulation in the context of important infectious diseases, namely HIV-1, malaria and Hepatitis C virus infection.  In each of these three diseases imbalances of iron are known to contribute to disease and mortality.  

For HIV-1, we found some years ago that the viral protein Nef targets the host protein HFE, which is dysfunctional in the iron-overloading disorder haemochromatosis.  By interacting with HFE, HIV manipulates iron transport in infected cells.  We are investigating the causes and consequences of altered iron metabolism and hepcidin levels in the context of HIV/AIDS.  In malaria, we have found that the blood stage of infection, associated with anaemia, causes an increase in hepcidin synthesis.  If we can block this induction of hepcidin by the parasite we may be able to alleviate malarial anaemia, which is a major cause of illness worldwide.  Finally, HCV infection can suppress hepcidin and lead to iron overload.  Increased iron is an important co-factor for morbidity in the context of HCV.  We are investigating the molecular basis for hepcidin suppression by HCV with a view to understanding more about HCV / liver interactions and potentially find new ways to inhibit viral replication.