Katherine de Villiers, Ph.D.

Katherine de Villiers is a senior lecturer in the Department of Chemistry and Polymer Science at Stellenbosch University in South Africa. Her research group is focused on understanding the heme detoxification pathway in the malaria parasite, Plasmodium falciparum. In the absence of the heme oxygenase machinery that is employed by mammals to catabolize heme, these parasites sequester toxic heme in the form of crystalline hemozoin, and disruption of this process underpins the mechanism of action of numerous clinical antimalarial drugs. The group uses spectrophotometric analyses to better understand the effect of inhibitors on the kinetics of synthetic hemozoin (β-hematin) formation, and has hypothesized that adsorption of inhibitors to the surface of growing crystals is an equilibrium process that reduces the rate of crystal growth. They have further proposed that the subsequent formation of inhibitor-heme complexes may contribute to the parasiticidal effects of inhibitors, and are responsible for the publication of the only known single crystal X-ray diffraction structures of antimalarial-heme complexes. A central theme to her current research is the “rational design” of new chemotherapeutic compounds.

de Villiers grew up in Zimbabwe, where she witnessed the severe impact of malaria on families and especially on young children. She obtained her Ph.D. in chemistry from the University of Cape Town in 2008 under the mentorship of the late Timothy Egan, who introduced her to the chemistry of heme and hemozoin and inspired her research path toward finding new cures for this devastating disease.

Research Blurb

Prior to her mentor’s seminal discovery in 2019 of hemozoin formation in mice where a particular heme transporter gene (HRG1) had been knocked out, hemozoin biocrystallization was only considered relevant to blood-feeding organisms that lacked heme oxygenase machinery. For the past twenty years, Katherine de Villiers has studied the chemistry of heme and hemozoin. As a Simons Foundation Pivot Fellow, she hopes to apply this knowledge to better understand the circumstances under which hemozoin formation is/becomes relevant in mammals. To this end, de Villiers looks forward to gaining expertise in molecular biology and genetics in order to dissect and understand the molecular pathways that function to regulate cellular heme levels. At the end of the fellowship, she hopes to understand the lysosomal conditions under which mammalian hemozoin formation is initiated, the impact of hemozoin inhibition on heme homeostasis, and whether there are alternate heme transport mechanisms in the absence of HRG1. Directly related to the regulation of heme is iron homeostasis (since iron is the central atom in every heme molecule), and in the future, de Villiers hopes to use her fellowship training to advance the understanding of diseases of excess iron such as African iron overload.