After completing a degree at Cambridge and medical degree at Oxford, I studied malaria in Thailand and molecular aspects of malaria for my DPhil at the Weatherall Institute of Molecular Medicine in Oxford. I joined St George’s in 2000 and was an Wellcome Trust Senior Research Fellow in Clinical Science (1994–2001). I was elected a Fellow of the Academy of Medical Sciences in 2004 and awarded an ScD by the University of Cambridge in 2007. I am also an honorary consultant physician in infectious disease and medicine at St George’s University Hospitals NHS Foundation Trust. I have been an advisor to multiple international bodies, including the World Health Organisation for malaria and COVID19 therapeutics. I also have strong industrial contacts, and have acted as scientific advisor to several biotech firms. Strong collaborative links have also been established with Universities or research groups in Malaysia, Germany, Gabon, India, France and Vietnam.
My research (www.tropmed.ac.uk) has focused on infectious disease, particularly malaria, encompassing diagnostics, the mechanism of action of drugs, identification of new drug targets, and clinical studies of drug responses and disease processes. Our group has a particular interest in parasite transporter proteins, which are targeted by existing antimalarial drugs and are also promising new targets. Our group has made numerous contributions across a wide range of translational and clinical research, including:
Artemisinins' mechanism of action: Identifying the SERCA/PfATP6 transporter as one target of the artemisinin antimalarial and highlighting that partner drug failure is the main cause of ACT treatment failures
Drug resistance: Identifying pfmdr1 copy number expansion as a predictor of treatment failure to commonly used antimalarial drugs; an assay used in this research is now used globally in epidemiological surveys of resistance carried out by the Worldwide Antimalarial Resistance Network (WWARN).
New drug targets: Confirming the Plasmodium glucose transporter (PfHT) as a valid antimalarial drug target; compounds targeting PfHT are in preclinical development and the structure has now been crystallised by other using the inhibitor that we first identified
Pathophysiological studies: Establishing the importance of and mechanisms underlying lactic acidosis and hypoglycaemia in children with severe malaria, and exploring potential treatments
Diagnostics: Improving staging of second stage human African trypanosomiasis with neopterin and developing new technologies for point-of-care testing for infections assessing drug resistance.
Emerging infections: COVID19: In response to the recent pandemic challenge (http://www.tropmed.ac.uk/blog), I have worked on many aspects of SARS-CoV-2 infection including diagnostics and treatment studies (see publications). I also led the UK’s only group that was part of the VEBCON consortium that developed the registered Ebola vaccine (VSV-ZEBOV).
Treatment & repurposing drugs: Leading clinical studies to establish optimal dosing regimens for artesunate and other antimalarial treatments, including life-saving rectal artesunate. Establishing the concept of repurposing artemisinins to treat cancers through a pilot randomised blinded controlled trial and current and planned Phase 1-2 studies. We are expanding clinical trials to HPV CIN2/3 stage disease, and leukaemias in efforts through an international consortium for affordable therapeutics.
I have also contributed an impact study on antimalarials for the Research Excellence Framework evaluation for our Institution (https://www.sgul.ac.uk/research/our-impact/research-excellence-framework/ref-2021/documents/REF3-UOA1-Krishna-impact-case-study-Optimising-malaria-treatment-with-artemisinins.pdf)