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

Professor of Cell Biology - - The Institute for Integrative Genome Biology - - The Center for Disease Vector Research

Biography

Le Roch Lab

Dr. Le Roch is a Professor of Cell Biology 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-Sorbonne, 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, as an Assistant, Associate and now Professor, Dr. Le Roch expanded her research scope by investigating new high-throughput functional genomics methods. In particular, her laboratory generated large genome-wide data sets using next generation sequencing technologies along with computational biology approaches, molecular and cellular biological techniques to understand key molecular mechanisms underlying the parasite development. 

Research Area:

We're searching for new strategies to combat malaria.

Malaria
With an estimate of 207 million cases of disease and close to 500,000 deaths every year, malaria represents one of the most important infectious diseases in the developing world. The absence of an efficient vaccine and the development of parasite resistance to all antimalarial drugs underscore the urgency for new therapeutic approaches. 

Our Research

Dr. Le Roch's 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, Dr. Le Roch 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 ubiquitin and ubiquitin-like systems.

One of the fundamental ways in which eukaryotic organisms regulate dynamic cellular processes is by invoking the ubiquitin and ubiquitin-like systems. As a central hub for protein turnover and post-translational modification, the ubiquitin and ubiquitin-like systems are important system for therapeutic intervention in a host of human diseases. In this model, similar to protein kinases, ubiquitin and ubiquitin-like proteins may serve as one of the major post-translational regulatory systems utilized by Plasmodium for its survival strategy. These pathways had never been investigated before in the field. Using functional genomics tools as well as molecular and cellular approaches, Dr. Le Roch laboratory undertook a multi-pronged effort to identify and characterize key components of the ubiquitin and ubiquitin-like systems in the parasite. Dr. Le Roch lab made a number of groundbreaking discoveries, most importantly, these molecular components are today not only targets for novel therapeutic intervention but are now carefully investigated for their involvement in parasite drug resistance. 

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. Dr. Le Roch laboratory was one of the first to develop the use of next generation sequencing technologies in parasite functional genomics. Her lab focused on understanding how change in chromatin structure can control the parasite gene expression. The lab is investigating changes in protein-DNA binding events: patterns of histone modifications, DNA methylation, nucleosome occupancy as well as large scale chromatin remodeling. Over the past few years, the Le Roch lab has efficaciously adapted and developed many new molecular, cellular and genome-wide tools to model gene expression in the parasite. For example, her laboratory was the first to publish FAIRE-seq as well as HI-C experiments throughout any eukaryotic cell cycle progression. The 3D model of the P. falciparum genome at three different stages in the parasite's life cycle was among the top 10 news Malaria stories of 2014. 

3. Drug discovery and natural products.

In addition to fundamental scientific approaches, The Le Roch lab is 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), Georgia Institute of technology, The University of
Puerto Rico or the University of California Irvin, are providing the lab with a comprehensive array of natural products. 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 also 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


List of Published Work - 69 peer-reviewed articles (Dec 2015): 
http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/40849273/?sort=date&direction=descending

5 most relevant publications on the parasite ubiquitin and ubiquitin-like systems.

  • Ponts N, Yang J, Chung DW, Prudhomme J, Girke T, Horrocks P, Le Roch KG. (2008). Deciphering the ubiquitin-mediated pathway in apicomplexan parasites: a potential strategy to interfere with parasite virulence. PLoS One. Jun 11;3(6):e2386. PMCID: PMC2408969.
  • Ponts N, Saraf A, Chung DW, Harris A, Prudhomme J, Washburn MP, Florens L, Le Roch KG. (2011). Unraveling the ubiquitome of the human malaria parasite. J Biol Chem. Nov 18;286(46):40320-30. Epub 2011 Sep 19. PMCID: PMC3220526.
  • Agrawal S, Chung DW, Ponts N, van Dooren GG, Prudhomme J, Brooks CF, Rodrigues EM, Tan JC, Ferdig MT, Striepen B, Le Roch KG. (2013) An apicoplast localized ubiquitylation system is required for the import of nuclear-encoded plastid proteins. PLoS Pathog. 9(6):e1003426. Epub 2013 Jun 13. PMCID: PMC3681736.
  • Hamilton MJ., Lee M., and Le Roch KG. The ubiquitin system:  an essential component to unlocking the secrets of malaria parasite biology.  Molecular BioSystems. 2014 Jan 30. [Epub ahead of print].
  • Cervantes S, Bunnik EM, Saraf A, Conner CM, Escalante A, Sardiu ME, Ponts N, Prudhomme J, Florens L, Le Roch KG. (2014). The multifunctional autophagy pathway in the human malaria parasite, Plasmodium falciparum. Autophagy. Jan;10(1):80-92. Epub 2013 Nov 11.  PMCID: PMC4028325.

5 most relevant publications for parasite chromatin structure.

  • Ponts N, Harris EY, Prudhomme J, Wick I, Eckhardt-Ludka C, Hicks GR, Hardiman G, Lonardi S, Le Roch KG. (2010). Nucleosome landscape and control of transcription in the human malaria parasite. Genome Res. Feb;20(2):228-38. Epub 2010 Jan 6. PMCID:PMC2813478.
  • Ponts N, Fu L, Harris EY, Zhang J, Chung DW, Cervantes MC, Prudhomme J, Atanasova-Penichon V, Zehraoui E, Bunnik EM, Rodrigues EM, Lonardi S, Hicks GR, Wang Y, Le Roch KG. (2013). Genome-wide mapping of DNA methylation in the human malaria parasite Plasmodium falciparum. Cell Host Microbe. Dec 11;14(6):696-706. PMCID: PMC3931529.
  • Bunnik EM., Chung DW, Hamilton M., Ponts N., Prudhomme J., and Le Roch KG. Polysome Profiling reveals Translational Control of Gene Expression 1 in the Human Malaria Parasite Plasmodium falciparum. Genome Biol. 2013 Nov 22;14(11):R128. [Epub ahead of print]
  • Bunnik EM, Polishko A, Prudhomme J, Ponts N, Gill SS, Lonardi S, Le Roch KG. (2014) DNA-encoded nucleosome occupancy is associated with transcription levels in the human malaria parasite Plasmodium falciparum. BMC Genomics. 2014 May 8;15:347. PMCID: PMC4035074.
  • Ay F, Bunnik EM, Varoquaux N, Bol SM, Prudhomme J, Vert JP, Noble WS, Le Roch KG. (2014). Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression. Genome Res. Jun;24(6):974-88. Epub 2014 Mar 26. PMCID: PMC4032861

5 most relevant and recent publications for Drug discovery and natural products.

  • Stout EP, Cervantes S, Prudhomme J, France S, La Clair JJ, Le Roch KG †  and Kubanek J. †  Bromophycolide A targets heme crystallization in the human malaria parasite Plasmodium falciparum. ChemMedChem. 2011 Jul 5. doi: 10.1002/cmdc.201100252. [Epub ahead of print]. † Contributed equally to this work.
  • Cervantes S., Stout E. P., Prudhomme J., Engel S., Burton M., Cervantes M., Carter D., Chang Y.T, Hay M.E., Aalbersberg W., Kubanek J. and Le Roch KG.  High Content Live Cell Imaging Evaluation for the Discovery of New Antimalarial Natural Products. BMC Infect Dis. 2012 Jan 3;12:1.
  • Teasdale M., Prudhomme, J., Torres M., Braley M.; Cervantes S., Bhatia S., La Clair J., Le Roch K. †, and Kubanek J†. Pharmacokinetics, metabolism, and in vivo efficacy of the antimalarial natural product bromophycolide A. ACS Medicinal Chemistry Letters 2013. Oct 10;4(10):989-
  • Daub ME, Prudhomme J, Le Roch K, Vanderwal CD. Synthesis and potent antimalarial activity of kalihinol B. J Am Chem Soc. 2015 Apr 22;137(15):4912-5. doi: 10.1021/jacs.5b01152. Epub 2015 Apr 9.
  • Aviles, E. Prudhomme, J., Le Roch, K. and Rodriguez, A.. Structures, semisyntheses, and absolute configurations of the antiplasmodial a-substituted b-lactam monamphilectines B and C from the sponge Svenzea flava. Tetrahedron, 2015 Jan 21;71(3):487-494.

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Cell Biology and Neuroscience
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David Eastmond: Chair of Cell Biology & Neurosience
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