Chemoprevention: a new approach to ending malaria

Elizabeth Ann Winzeler is a Professor at the University of California, San Diego, School of Medicine. She leads a group that uses systematic, data intensive methods to solve problems at the interface of host pathogen biology typically involving large collections of chemical screening data and whole genome sequencing at UC San Diego. She is a fellow of the American Academy in Microbiology. She has published more than 150 publications. She has received awards from the Keck Foundation, the Ellison Medical Foundation, and the Bill and Melinda Gates Foundation. In 2014 she was awarded the Bailey-Ashford Medal for distinguished achievements in tropical medicine, she received the 2017 Medicines of Malaria Venture Project of the Year and in 2018 she has received the Alice and C.C. Wang Award in Molecular Parasitology and the William Trager Award on behalf of ASTMH and the American Committee of Molecular, Cellular and Immunoparasitology. 

Malaria remains a devastating disease, affecting 216 million people annually with 445,000 deaths occurring primarily in children under five.  Malaria treatment relies primarily on drugs that target the disease-causing asexual blood stages (ABS) of Plasmodium parasites, the organisms responsible for human malaria.  While travelers may rely on short-term daily chemoprotective drugs, those living in endemic regions require long-term malaria protection such as insecticide-treated nets (ITNs) and vector control.  However, ITNs do not fully shield individuals from malaria, may lose potency with time and can be bulky and difficult to use.  Another concern is that mosquitos may become resistant to the active insecticides that are used in ITNs and vector control.

As the possibility of malaria elimination becomes more tangible, the ideal antimalarial medicine profile should include chemoprotection. Chemoprotective medicines typically work against the exoerythrocytic parasite forms which invade and develop in the liver and are responsible for the earliest asymptomatic stage of the infection.  Such medicines could be formulated to provide long-acting prophylaxis, safeguarding individuals that are living near or traveling to areas that have been cleared of parasites.  Long-acting chemoprotection in endemic regions could also greatly reduce circulating parasite numbers and potentially replace a vaccine in an elimination campaign. 

We are using multiple complimentary approaches, including the discovery of chemically-validated drug targets, phenotypic screening, and studies into host parasite interactions.  Our data are revealing new chemotypes that act against the parasite mitochondria, parasite lipid production, protein biosynthesis pathways or which disrupt host pathogen signaling and which are attractive starting points for chemopreventative drug discovery.    

Open-source discovery of chemical leads for next-generation chemoprotective antimalarials

Y Antonova-Koch, S Meister, M Abraham, MR Luth, S Ottilie, AK Lukens, ...

Science 362 (6419), eaat9446

Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics

AN Cowell, ES Istvan, AK Lukens, MG Gomez-Lorenzo, M Vanaerschot, ...

Science 359 (6372), 191-199    

This seminar will be NOT be livestreamed or recorded.