Skills (51)
Research experience
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Jan 2008–
presentResearch: Characterizing the role of alternative splicing factors in mammary epithelial cell transformation
Cold Spring Harbor Laboratory · Krainer LabUSA · Cold Spring HarborCharacterizing the role of alternative splicing factors in mammary epithelial cell transformation by using 3-D cell culture and animal models that mimic the breast microenvironnement. -
Jan 2005–
Feb 2005Research: Dissecting mRNA decay mechanisms in breast cancer
Molecular Medicine Partnership Unit (EMBL-Heidelberg University)Germany · HeidelbergCharacterized the stability of transcript containing mutations in breast cancer predisposing genes. Improved outcome prediction and disease classification based on the position of mutations in the BRCA1 and CHECK2 genes. -
Sep 2002–
Dec 2007Research: Assessing the molecular consequences of mutations in breast cancer predisposing genes
Molecular Genetics, Signalling and Cancer Lab (CNRS Lyon, France)France · LyonCharacterized the molecular consequences a panel of germline mutations in breast cancer predisposing genes BRCA1 and CHECK2. Contributed to improve molecular diagnostic and classification of hereditary breast cancers. -
Jun 2002–
Sep 2002Research: Characterizing acetyl-coA carboxylase mutations in breast cancer
International Agency for Research on Cancer (WHO)France · LyonCharacterized the gene structure of a putative breast cancer predisposing gene involved in fatty acid synthesis. Participated in the screening of the acetyl-coA carboxylase gene for mutations in a cohort of breast cancer patients. -
Jun 2001–
Sep 2001Research: Screening for mutations in the DNAI2 gene in Primary ciliary dyskinesia
Medical School of Lyon · Human Molecular Genetics LabFrance · LyonScreened the DNAI2 gene for mutations in a cohort of patients with Primary ciliary dyskinesia, a rare genetic disease.
Education
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Sep 2003–
Dec 2007Université Claude Bernard Lyon 1
Molecular genetics · PhDFrance · Villeurbanne -
Sep 2002–
Sep 2003Ecole normale supérieure de Lyon
Molecular and Cellular Biology · MSFrance · Lyon -
Sep 2000–
Sep 2001Ecole normale supérieure de Lyon
Molecular and Cellular Biology · BASFrance · Lyon
Awards & achievements
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Oct 2011Award: AACR Scholar-in-Training Award, Advances in Breast Cancer Research Conference
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Apr 2010Award: AACR Susan Komen Scholar-in-Training Award, AACR 101st Annual Meeting
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Oct 2009Scholarship: AACR Scholar in Training Award, Advances in Breast Cancer Research Conference
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Jun 2009Grant: Susan Komen Breast Cancer Foundation Postdoctoral fellowship
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Jun 2009Grant: Department of Defense Breast Cancer Research Program, Postdoctoral fellowship
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Jun 2008Award: Philippe Foundation
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Jan 2008Grant: French Foundation for Medical Research (FRM), Postdoctoral fellowship
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Jun 2007Scholarship: French Cancer Research Foundation (ARC), PhD fellowship
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Sep 2004Scholarship: French Cancer Research Foundation (Ligue Contre le Cancer), PhD Fellowship
Other
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LanguagesEnglish
French
Polish
German -
Scientific MembershipsAACR
RNA Society
Questions and Answers (17) View all
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Answer added in RNA4 Weird 28s and 18s rna bandHi, The most important is that you have two nice bands, and no visible signs of degradation, and the bands definitively look like 28S and 18S RNA ! A... [more]
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Answer added in mRNA3 What is the best technique to identify alternative slicing result in vivo and in vitro ?Hi, There are many ways of identifying alternative splicing events, either by whole-transcriptome analysis or gene specific assays. For global anal... [more]
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Answer added in Cell Signaling7 What serum concentration and medium components would you use for serum starvation of fibrosarcoma cell line?Serum starvation is usually 0.1% or 0% of serum overnight. But it all depends what you are trying to achieve ? Best
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Answer added in Gel Electrophoresis11 Does anyone have experience with the Nucleospin RNA/Protein extraction kit? Why does the RNA I extract always show only 1 band on a 1% Agarose gel?Hi, I never used the RNA/Protein kit, but I used the Nucleospin RNA II before and it worked really great. First question, what is the concentration o... [more]
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Answer added in Plant Biotechnology18 Problem with real time PCR curveIf despite all the suggestions, it still does not work, then you should consider changing the primers, and testing different sets in order to find eff... [more]
Publications (9) View all
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Article: BRCA2 Deep Intronic Mutation Causing Activation of a Cryptic Exon: Opening toward a New Preventive Therapeutic Strategy.
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ABSTRACT: Diagnostic screening of the BRCA1/2 genes in breast cancer families is mostly done on genomic DNA. For families with a very strong family history and no mutation identified in the coding sequences or the exon-intron boundaries, BRCA1/2 transcripts' analysis is an efficient approach to uncover gene inversion and pre-mRNA splicing defaults missed by conventional DNA-based protocols. We analyzed RNA from patients of negative BRCA families by reverse transcriptase PCR and identified an insertion in one family that we characterized by sequencing and by using a minigene splicing assay. More than 2,000 additional BRCA1/2 negative families were subsequently screened for this mutation using a dedicated PCR approach. Nine families were found to harbor a BRCA2 mutant transcript containing a 95-nucleotide cryptic exon between exons 12 and 13. This cryptic exon results from a new mutation located deep into intron 12, c.6937+594T > G, which reinforces the strength of a preexisting 5' splice site, turning it into a perfect consensus sequence. It is systematically included in transcripts produced by the mutant allele in cells from mutation carriers or produced by a mutant splicing reporter minigene. The inclusion of the cryptic exon was prevented when we cotransfected the minigene with antisense oligonucleotides complementary to the 3' or mutated 5' splice sites. This first deep intronic BRCA mutation emphasizes the importance of analyzing RNA to provide comprehensive BRCA1/2 diagnostic tests and opens the possibility of using antisense therapy in the future as an alternative strategy for cancer prevention. Clin Cancer Res; 18(18); 4903-9. ©2012 AACR.Clinical Cancer Research 07/2012; 18(18):4903-9. · 7.74 Impact Factor -
Article: OLego: fast and sensitive mapping of spliced mRNA-Seq reads using small seeds.
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ABSTRACT: A crucial step in analyzing mRNA-Seq data is to accurately and efficiently map hundreds of millions of reads to the reference genome and exon junctions. Here we present OLego, an algorithm specifically designed for de novo mapping of spliced mRNA-Seq reads. OLego adopts a multiple-seed-and-extend scheme, and does not rely on a separate external aligner. It achieves high sensitivity of junction detection by strategic searches with small seeds (∼14 nt for mammalian genomes). To improve accuracy and resolve ambiguous mapping at junctions, OLego uses a built-in statistical model to score exon junctions by splice-site strength and intron size. Burrows-Wheeler transform is used in multiple steps of the algorithm to efficiently map seeds, locate junctions and identify small exons. OLego is implemented in C++ with fully multithreaded execution, and allows fast processing of large-scale data. We systematically evaluated the performance of OLego in comparison with published tools using both simulated and real data. OLego demonstrated better sensitivity, higher or comparable accuracy and substantially improved speed. OLego also identified hundreds of novel micro-exons (<30 nt) in the mouse transcriptome, many of which are phylogenetically conserved and can be validated experimentally in vivo. OLego is freely available at http://zhanglab.c2b2.columbia.edu/index.php/OLego.Nucleic Acids Research 04/2013; · 8.03 Impact Factor -
Article: Comparison of nonsense-mediated mRNA decay efficiency in various murine tissues.
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ABSTRACT: The Nonsense-Mediated mRNA Decay (NMD) pathway detects and degrades mRNAs containing premature termination codons, thereby preventing the accumulation of potentially detrimental truncated proteins. Intertissue variation in the efficiency of this mechanism has been suggested, which could have important implications for the understanding of genotype-phenotype correlations in various genetic disorders. However, compelling evidence in favour of this hypothesis is lacking. Here, we have explored this question by measuring the ratio of mutant versus wild-type Men1 transcripts in thirteen tissues from mice carrying a heterozygous truncating mutation in the ubiquitously expressed Men1 gene. Significant differences were found between two groups of tissues. The first group, which includes testis, ovary, brain and heart, displays a strong decrease of the nonsense transcript (average ratio of 18% of mutant versus wild-type Men1 transcripts, identical to the value measured in murine embryonic fibroblasts). The second group, comprising lung, intestine and thymus, shows much less pronounced NMD (average ratio of 35%). Importantly, the extent of degradation by NMD does not correlate with the expression level of eleven genes encoding proteins involved in NMD or with the expression level of the Men1 gene. Mouse models are an attractive option to evaluate the efficiency of NMD in multiple mammalian tissues and organs, given that it is much easier to obtain these from a mouse than from a single individual carrying a germline truncating mutation. In this study, we have uncovered in the thirteen different murine tissues that we examined up to a two-fold difference in NMD efficiency.BMC Genetics 01/2009; 9:83. · 2.47 Impact Factor -
Article: Oncogenic splicing factor SRSF1 is a critical transcriptional target of MYC.
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ABSTRACT: The SR protein splicing factor SRSF1 is a potent proto-oncogene that is frequently upregulated in cancer. Here, we show that SRSF1 is a direct target of the transcription factor oncoprotein MYC. These two oncogenes are significantly coexpressed in lung carcinomas, and MYC knockdown downregulates SRSF1 expression in lung-cancer cell lines. MYC directly activates transcription of SRSF1 through two noncanonical E-boxes in its promoter. The resulting increase in SRSF1 protein is sufficient to modulate alternative splicing of a subset of transcripts. In particular, MYC induction leads to SRSF1-mediated alternative splicing of the signaling kinase MKNK2 and the transcription factor TEAD1. SRSF1 knockdown reduces MYC's oncogenic activity, decreasing proliferation and anchorage-independent growth. These results suggest a mechanism for SRSF1 upregulation in tumors with elevated MYC and identify SRSF1 as a critical MYC target that contributes to its oncogenic potential by enabling MYC to regulate the expression of specific protein isoforms through alternative splicing.Cell reports. 02/2012; 1(2):110-7. -
Article: The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation.
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ABSTRACT: The splicing-factor oncoprotein SRSF1 (also known as SF2/ASF or ASF/SF2) is upregulated in breast cancers. We investigated the ability of SRSF1 to transform human and mouse mammary epithelial cells in vivo and in vitro. SRSF1-overexpressing COMMA-1D cells formed tumors, following orthotopic transplantation to reconstitute the mammary gland. In three-dimensional (3D) culture, SRSF1-overexpressing MCF-10A cells formed larger acini than control cells, reflecting increased proliferation and delayed apoptosis during acinar morphogenesis. These effects required the first RNA-recognition motif and nuclear functions of SRSF1. SRSF1 overexpression promoted alternative splicing of BIM (also known as BCL2L11) and BIN1 to produce isoforms that lack pro-apoptotic functions and contribute to the phenotype. Finally, SRSF1 cooperated specifically with MYC to transform mammary epithelial cells, in part by potentiating eIF4E activation, and these cooperating oncogenes are significantly coexpressed in human breast tumors. Thus, SRSF1 can promote breast cancer, and SRSF1 itself or its downstream effectors may be valuable targets for the development of therapeutics.Nature Structural & Molecular Biology 02/2012; 19(2):220-8. · 12.71 Impact Factor
