Sign In

​Current Research

Plasmodium falciparum is the deadliest form of human malaria, causing the death of over million people annually. The virulence of P. falciparum is attributed to its ability to evade the human immune system, by modifying the host red blood cell surface to adhere to the vascular endothelium and to undergo antigenic variation.
This is achieved by tight regulation of gene expression that ensures that only a single gene (var) out of a large repertoire is expressed at a time. Understanding the molecular mechanisms by which the parasite evades human immune attack could lead to the development of new drugs that disrupt this ability and would give the human immune system an opportunity to clear the infection and overcome the disease. The ongoing research in my lab focuses on the molecular and cellular mechanisms that control gene expression in P. falciparum.
Mechanisms of virulence gene expression: We are interested to characterize cis and trans acting elements involved in the epigenetic regulation of var genes. Particularly, identification of the protein/s that specifically binds the insulator-like DNA elements required for var silencing and mutually exclusive expression. In addition we found that intronic antisense ncRNAs are associated with var gene activation and we investigate their possible role in regulation of these genes. We also study the unknown function and regulation of the unusual type3 vars. To ease the use of reverse genetic approaches in P. falciparum we develop new tools to manipulate gene expression in Plasmodium that could be also used as a novel approach for drug design.
Determination of the role of components of the nuclear envelope in gene regulation of malaria parasites. In addition to our efforts that will include whole genome approaches to determine the possible role of PfSec13 in the nucleoplasm, we identified additional nucleoporin homologues and we would like to investigate their association with gene expression in P. falciparum. We currently use bioinformatic, genetic and biochemical approaches to identify and characterize additional components of the NE and unveil their role in the parasites' biology.
The role of alternative splicing in regulating gene expression. Our identification of PfSR1 as the first alternative splicing factors in the Plasmodium encourage us to take whole genome approaches to explore its role in regulating gene expression. We created transgenic parasite that allow induced over expression of PfSR1 and will use them for Microarray and RNAseq to look at the global changes in transcription and AS that will enable to understand the importance of such event in parasites' biology. We currently characterize other candidate SR proteins that were identifies in our recent paper. In addition, target genes of PfSR1 will be used to establish artificial mini gene systems that will facilitate exploring mechanisms of AS in P. falciparum.