UCR

Cell Biology and Neuroscience



Karine Le Roch


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Phone: (951) 827-5422
Fax: (951) 827-3087
Office Location: 2121B Genomics
Office Hours:
Email: karine.leroch@ucr.edu

Karine Le Roch

Associate Professor
The Institute for Integrative Genome Biology
The Center for Disease Vector Research

Biography

Le Roch Lab

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.

Research Area:

We're searching for new strategies to combat malaria

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
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.


Areas of expertise:

  • Drug discovery/natural products
  • Transcriptional profiling / Microarray technologies
  • Functional genomics
  • Chromatin structure and epigenetics
  • Next generation sequencing technology (Illumina)
  • Cell cycle progression
  • Kinases and ubiquitin /proteasome pathway
  • Proteomics

Publications

  • Doug Chung DW, Ponts N, Cervantes S and Le Roch KG: Post-translational modifications in Plasmodium: More than you think! Mol Biochem Parasitol 2009.
  • Cervantes S, Prudhomme J, Carter D, Gopi KG, Li Q, Chang YT and Le Roch KG: High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery. BMC Cell Biol 2009, 10:45.
  • Lane AL, Stout EP, Lin AS, Prudhomme J, Le Roch K, Fairchild CR, Franzblau SG, Hay ME, Aalbersberg W, Kubanek J: Antimalarial bromophycolides J-Q from the Fijian red alga Callophycus serratus. J Org Chem 2009, 74(7):2736-2742.
  • Prudhomme J, McDaniel E, Ponts N, Bertani S, Fenical W, Jensen P and Le Roch K: Marine actinomycetes: a new source of compounds against the human malaria parasite. PLoS One 2008, 3(6):e2335.
  • Ponts N, Yang J, Chung DW, Prudhomme J, Girke T, Horrocks P and Le Roch KG: Deciphering the ubiquitin-mediated pathway in apicomplexan parasites: a potential strategy to interfere with parasite virulence. PLoS One 2008, 3(6):e2386.
  • Le Roch KG, Johnson JR, Ahiboh H, Chung DW, Prudhomme J, Plouffe D, Henson K, Zhou Y, Witola W, Yates JR et al: A systematic approach to understand the mechanism of action of the bisthiazolium compound T4 on the human malaria parasite, Plasmodium falciparum. BMC Genomics 2008, 9:513.
  • Kato N, Sakata T, Breton G, Le Roch KG, Nagle A, Andersen C, Bursulaya B, Henson K, Johnson J, Kumar KA et al: Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility. Nat Chem Biol 2008, 4(6):347-356.
  • Daily JP, Scanfeld D, Pochet N, Le Roch K, Plouffe D, Kamal M, Sarr O, Mboup S, Ndir O, Wypij D et al: Distinct physiological states of Plasmodium falciparum in malaria-infected patients. Nature 2007, 450(7172):1091-1095.
  • Kidgell C, Volkman SK, Daily J, Borevitz JO, Plouffe D, Zhou Y, Johnson JR, Le Roch K, Sarr O, Ndir O et al: A systematic map of genetic variation in Plasmodium falciparum. PLoS Pathog 2006, 2(6):e57.
  • Le Roch KG, Johnson JR, Florens L, Zhou Y, Santrosyan A, Grainger M, Yan SF, Williamson KC, Holder AA, Carucci DJ et al: Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle. Genome Res 2004, 14(11):2308-2318.
  • Le Roch KG, Zhou Y, Blair PL, Grainger M, Moch JK, Haynes JD, De La Vega P, Holder AA, Batalov S, Carucci DJ et al: Discovery of gene function by expression profiling of the malaria parasite life cycle. Science 2003, 301(5639):1503-1508.
  • Volkman SK, Hartl DL, Wirth DF, Nielsen KM, Choi M, Batalov S, Zhou Y, Plouffe D, Le Roch KG, Abagyan R et al: Excess polymorphisms in genes for membrane proteins in Plasmodium falciparum. Science 2002, 298(5591):216-218.
  • Le Roch KG, Zhou Y, Batalov S, Winzeler EA: Monitoring the chromosome 2 intraerythrocytic transcriptome of Plasmodium falciparum using oligonucleotide arrays. Am J Trop Med Hyg 2002, 67(3):233-243.
  • Le Roch K, Sestier C, Dorin D, Waters N, Kappes B, Chakrabarti D, Meijer L, Doerig C: Activation of a Plasmodium falciparum cdc2-related kinase by heterologous p25 and cyclin H. Functional characterization of a P. falciparum cyclin homologue. J Biol Chem 2000, 275(12):8952-8958.

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Cell Biology and Neuroscience
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David Eastmond: Chair of Cell Biology & Neurosience
Tel: (951) 827-4497
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E-mail: david.eastmond@ucr.edu

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