UC Riverside

The unicellular protozoan, Plasmodium falciparum, is the human malaria-causing parasite responsible for over half a million deaths each year. P. falciparum has a complex life cycle, alternating between human and invertebrate hosts, and is capable of not only evading the host immune responses but also developing resistance to all clinically administered treatments. Consequently, malaria remains a persistent global health concern. Recent advances in omics-based technologies, improved sequencing platforms, and enhanced CRISPR-based gene editing tools have opened new avenues for understanding the parasite biology, identifying new therapeutic strategies and combating the spread of malaria.This report delves into the systems-wide approaches employed to explore the drug mechanism of action of a new compound, MED6-189, a new analogue of the kalihinol family of isocyanoterpene natural products, effective against drug-sensitive and -resistant P. falciparum strains. We also use advance multi-omics strategies to identify and functionally characterize new potential drug targets involved in gene regulation. Those included targeting proteins coding for chromatin remodeling complexes or better understanding the role of long non-coding RNAs (lncRNA) in the parasite life cycle progression. In essence, the goal of my PhD thesis was to identify promising and alternative targets to curb the spread of malaria, either through the development of new antimalarial agents or the discovery of novel, unexploited potential targets critical for the parasite's survival.