Hiran A. Prag
I am currently interested in the role of mitochondria in ischaemia/reperfusion (I/R) injury, occurring in heart attack, stroke and organ transplantation. In particular, I am interested in the role of the mitochondrial metabolite succinate and the role it plays in the production of reactive oxygen species (ROS) in the damaging events and signalling. By perturbing succinate metabolism, I hope to develop new therapeutic strategies to ameliorate I/R injury.
Absolute quantification of succinate (and other mitochondrial metabolites) from tissues and cells is carried out using a Shimadzu LC-8060.
• Prag, H.A., Gruszczyk, A.V., Huang, M.M et al. Mechanism of succinate efflux upon reperfusion of the ischemic heart. Cardiovascular Research (2020) DOI: 10.1093/cvr/cvaa148.
• Prag, H.A., Kula-Alwar, D., Pala, L. et al. Selective delivery of dicarboxylates to mitochondria by conjugation to a lipophilic cation via a cleavable linker. Molecular Pharmaceutics (2020) DOI: 10.1021/acs.molpharmaceut.0c00533
• Prag, H.A., Pala, L., Kula-Alwar, D. et al. Ester prodrugs of malonate with enhanced intracellular delivery protect against cardiac ischemia-reperfusion injury in vivo. Cardiovascular Drugs and Therapy (2020) DOI:10.1007/s10557-020-07033-6
• Kula-Alwar, D.*, Prag, H.A.* & Krieg, T. Targeting succinate metabolism in ischemia/reperfusion injury. Circulation 140, 1968–1970 (2019)
• Mills, E.L., Ryan, D.G., Prag, H.A. et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556, 113–117 (2018)
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