Marcus Lee is interested in the molecular basis of drug resistance in the human malaria parasite Plasmodium falciparum, and in developing molecular genetics approaches to interrogate gene function.
An individual malaria infection can be driven by more than 100 billion parasites at the peak of the disease cycle. Over the course of a chronic infection, the parasite has the potential to mutate at rates that suggest an enormous capacity to develop vast genetic diversity. This latent variability has troubling implications for the ease with which the parasite might develop immunity to drug treatment, both current and future. In the field, clinical resistance can take as little as a year to develop or can accrue over decades.
One of my longstanding research interests has been to understand the mechanisms available to the parasite to develop resistance, which often comes at a cost in terms of fitness in the absence of drug pressure. We hope to guide the development and prioritization of future therapeutic targets and gain fundamental biological insights into critical parasite pathways.
A key bottleneck in the historical interrogation of drug resistance mechanisms has been the ability to manipulate the parasite genome. Establishing the causality of given phenotypes relies on the precise query of distinct resistance-associated alleles.
We are developing new molecular genetics approaches that harness CRISPR/Cas to apply systems-level analysis to parasite fitness and drug tolerance. In this work we collaborate closely with the labs of Julian Rayner and Oliver Billker. Our work also directly complements genome-wide association studies that have identified candidate loci involved in emerging drug resistance and clinical treatment failure.
Joined Wellcome Sanger Institute
Associate Research Scientist at Columbia University Medical Center
Moved to Columbia University Medical Center with David Fidock
NIH NRSA Postdoctoral Fellowship with David Fidock at Albert Einstein College of Medicine
Human Frontier Science Program Postdoctoral Fellowship with Randy Schekman at University of California Berkeley
Awarded PhD from University of Melbourne, on the study of plant defense proteins with Marilyn Anderson