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Sylvain Costes

biophysicist: Life Sciences Division

Media contact: Dan Krotz, 510-486-4019, dakrotz@lbl.gov

 

The Costes laboratory specializes in computational biology. Areas of expertise:

1. Radiation biology

2. Modeling and radiation system biology

3. Three-dimensional microscopy

4. High-content image analysis

5. Three-dimensional human mammary epithelial cell cultures known to mimic human breast in vitro are the primary biological systems used in the lab. These systems have been used to quantify the effect of ionizing radiation at the DNA and extra-cellular level.

Recent research

The Costes lab is currently working on two interdisciplinary projects:

NASA Specialized Center of Research (NSCOR) 

1. Modeling DNA damage patterns in human cells exposed to cosmic radiation. 

The spatial distribution of DNA damage measured by markers such as phosphorylated histone H2AX or p53 binding protein 1 (53BP1) were compared to theoretical predictions from a mathematical model developed in our lab. These comparisons led to the conclusion that damages are not detected at their original site of damage, but instead at specific location in the nucleus. Our lab is currently investigating if this is the result of nuclear reorganization following ionizing radiation or the clustering of DNA damage into repair centers. Reorganization of damages into specific regions in the nucleus has important consequences for evaluating risk of cosmic rays on human, a topic of interest for our lab as well.

2. Modeling disruption of organized cell population following ionizing radiation.

We are currently establishing an agent-based model that mimics cell behavior when grown as monolayer or in three-dimension. These in silico cell cultures are currently being used to test the impact of radiation on cell death, cell proliferation and how this translates at the phenotype level.

 

DOE Low-Dose Radiation Program

This project evaluates chromatin modifications following exposure to low dose of low-LET radiation. We are working under the current hypothesis that DNA damage elicits chromatin modification necessary for DNA repair which can lead in some cases to permanent changes in the epigenetic status of a cell. Dr. Costes group focuses on characterizing by image analysis permanent changes in chromatin organization in primary and immortalized human mammary epithelial cells (HMEC) and fibroblasts at different time points after low and high dose irradiation. This type of studies offers an alternative mechanism for explaining persistent phenotype acquired following exposure to ionizing radiation such as Epithelial-Mesenchymal Transition (EMT) or Genomic Instability (GI).

Recent Publications

Mukhopadhya R., Costes S.V., Bazarov A., Hines W.C., Barcellos-Hoff M.H., Yaswen P. Promotion of variant human mammary epithelial cell outgrowth by ionizing radiation: an agent-based model supported by in vitro studies. Breast Cancer Research (2010).

Costes S.V., Chiolo I., Pluth J.M., Barcellos-Hoff M.H. and Jakob B. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization. Mutat Res (2010).

Ghajar C.M., Kachgal S., Kniazeva E., Mori H., Costes S.V., George S.C. and Putnam A.J. Mesenchymal cells stimulate capillary morphogenesis via distinct proteolytic mechanisms. Exp Cell Res (2010).

Ponomarev A.L., Costes S.V., Cucinotta F.A.Stochastic properties of radiation-induced DSB: DSB distributions in large scale chromatin loops, the HPRT gene and within the visible volumes of DNA repair foci, Int J Radiat Biol. 2008 Nov;84(11):916-29.

Maxwell C.A., Fleisch M.C., Costes S.V., Erickson A.C., Boissiere A., Gupta R., Ravani S.A., Parvin B., Barcellos-Hoff M.H. Targeted and non-targeted effects of ionizing radiation that impact genomic instability. Cancer Res. 2008 Oct 15;68(20):8304-11.

Barkan D., Kleinman H., Simmons J.L., Asmussen H., Kamaraju A.K., Hoenorhoff M.J., Liu Z.Y., Costes S.V., Cho E.H., Lockett S., Khanna C., Chambers A.F., Green J.E. Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer Res. 2008 Aug 1;68(15):6241-50.

Awards and Memberships

Earl C. Anthony Fellowship and Regents Fellowship, University of California

Outstanding Graduate Student Instructor in Nuclear Physics & Biophysics, University of California

Student Travel Award, Radiation Research Society

Invited speaker at 35 different scientific meetings symposiums or seminars

Outstanding Achievement Award, Cancer System Biology Division, Lawrence Berkeley Lab

Reviewer for Journal of theoretical Biology, Radiation Research, European Journal of Cell Biology and Cytometry

Member of the Radiation Research Society and the American Association for Cancer Research

Imaging consultant for Carl Zeiss since July 2006

Member of  Radiation Research Podcast Team

Education

Postdoctoral studies: Quantitative Biology, University of California, Berkeley

Ph.D. Nuclear Engineering and Radiation Biology, University of California, Berkeley

M.S., Nuclear Engineering, Texas A&M University

M.S., Physics & Mathematics, Ecole Nationale Supérieure de Physique de Grenoble



last updated: 2012-06-29 16:32:35