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Le Roch, Karine G
Dr. Le Roch is an assistant professor at the University of California, Riverside (UCR). She obtained her master’s degree in Parasitology at the University of Lille II and the University of Oxford, in 1997. She completed her Ph.D. in June 2001 at the University of Paris VI, working on the cell cycle regulation of the human malaria parasite, Plasmodium falciparum. In 2001, as a postdoctoral fellow, she joined the Scripps Research Institute, San Diego, California to carry out the functional analysis of the P. falciparum genome using microarray technologies. She joined the Genomics Institute of the Novartis Research Foundation (California) in January 2004 where she developed the malaria drug discovery program. Since April 2006 at UCR, Dr. Le Roch is using functional genomics approaches such as proteomics and high-throughput sequencing technologies to elucidate critical regulatory networks driving the malaria parasite life cycle progression and identify novel drug targets.
UC San Diego
We're searching for new strategies to combat malaria
With an estimate of 400,000 new infections and up to one million deaths per year, malaria represents one of the most important infectious diseases in the developing world. The absence of a vaccine and the development of parasite resistance to commonly used antimalarial drugs underscore the urgency for new therapeutic approaches. The goal of our research is to define a novel line of defense and characterize innovative critical drug targets.
Our research focuses on developing biological and technological tools to dissect the molecular events driving the human malaria parasite life cycle progression. Using functional genomics approaches, we expect to elucidate critical regulatory networks driving the parasite life cycle and identify novel therapeutic strategies. There are three main research projects ongoing in the laboratory
1. Understanding the parasite ubiquitination system One of the fundamental ways in which eukaryotic organisms regulate dynamic cellular processes is by invoking the ubiquitin/proteosome system (UPS). As a central hub for protein turnover and post-translational modification, the UPS is being showcased as an important system for therapeutic intervention in a host of human diseases. Today, the laboratory is undertaking a multi pronged effort to identify components and key mechanisms of the ubiquitination system in malaria. We are employing the power of comparative genomics to discover unique apicomplexan proteins while utilizing advanced genomics and proteomic techniques to analyze the function of parasite specific ubiquitin-ligases. Ultimately, our main goal is to target disease relevant regulatory events in the parasite life cycle.
2. Revealing the parasite chromatin structure and its role in transcriptional regulation Mechanisms controlling gene expression in the parasite are still poorly understood. Rising evidences indicate that control of gene expression in P. falciparum occurs at multiple levels, one of those being chromatin remodeling. It is increasingly apparent that histone turnover and histone post-translational modifications are important in chromatin structure and transcriptional regulation. Determination of chromatin’s structural changes will therefore be critical for the understanding of transcriptional regulation in Plasmodium. Using next generation sequencing technology and histone pull down followed by mass spectrometry analyses; we are investigating the parasite dynamic nucleosome landscapes.
3. Drug discovery and natural products In addition to fundamental scientific approaches, we are developing drug-screening assays and high content live cell confocal imaging technologies to identify small molecule inhibitors and their morphological effects on the human malaria parasite. Ongoing collaborations with the Scripps Oceanography Institute (San Diego, CA) and the Georgia Institute of technology are providing us with a comprehensive array of marine extracts. So far we have already uncovered several compounds that can inhibit malaria growth in the low nano molar ranges. Experiments to identify drug targets and drug mechanism of actions are still ongoing.
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