Ph.D with 5 years postdoctoral experience and a broad interest in molecular biology.
Professional experiences

Jul. 2006-present: Postdoctoral Fellow
Project: Development of a cell-free assay for screening of compounds that modulate the Fanconi anemia/BRCA DNA repair pathway.
Laboratory:  Dr. Maureen E. Hoatlin, Dept. of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, Oregon.

Re-sensitizing tumor cells that have become resistant to common chemotherapeutic DNA interstrand crosslinking agents like cisplatin and melphalan has great potential for treating a wide variety of cancers. One approach is to inhibit DNA damage response pathways involved in DNA interstrand crosslink (ICL) repair. In particular, the breast cancer associated (BRCA)/ Fanconi Anemia (FA) DNA damage response pathway is required for cell survival after exposure to DNA ICLs.
We designed a novel in vitro assay using Xenopus egg extracts to identify small molecules that suppress activation of the BRCA/FA pathway. The assay is based on the monitoring of the DNA-substrate stimulated monoubiquitylation of a protein central to the pathway, FANCD2.
To assess the validity of the system, we screened analogs of curcumin, an inhibitor of the FA pathway recently identified in cell-based assays (Chirnomas, et al., 2006). Among 38 analogs tested, 4 displayed higher activity than curcumin in the Xenopus assay. These results were confirmed in human cells since 3 of the compounds sensitized Fanconi anemia-competent cells to crosslinking agents at concentrations 10-50 times lower than curcumin (the fourth is still under investigation). In contrast, these compounds did not sensitize the isogenic Fanconi-deficient cell line, suggesting that they target the BRCA/FA pathway.  We also screened 372 compounds from targeted small molecule libraries and identified several previously unknown inhibitors of the BRCA/FA pathway.  Follow-up analysis in human cells demonstrated that at least one compound inhibited the DNA damage-induced monoubiquitylation and foci formation of FANCD2 and chemosensitized cells to DNA crosslinking agents.
This approach provides the first example of a rapid and inexpensive in vitro assay for identifying compounds that modulate the BRCA/FA pathway, bridging the gap between biochemical and cell-based assays. Furthermore, because Xenopus egg extracts are naturally synchronized in S-phase, this assay is uniquely suited for identification and targeting of modifications occurring during S-phase. Indeed, in addition to FANCD2 monoubiquitylation, we found that at last 7 other DNA repair proteins are post-translationally modified in our assay. Hence, this system has a strong potential for development as a high-thoughput and multiple target screening tool.

Jan. 2003-Jun. 2006: Postdoctoral Fellow
Project: Regulation of the stability of the transcription elongation factor FACT.
Laboratory:  Dr.Hua Lu, Dept. of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, Oregon.

FACT (Facilitates Chromatin Transcription) has been identified as a key factor for transcriptional elongation. FACT is believed to relieve chromatin-mediated transcriptional repression by promoting nucleosome disassembly through the selective removal of one histone H2A-H2B dimer. FACT has also been linked with DNA replication, recombination and DNA-damage response. Our lab recently demonstrated that UV irradiation causes human FACT to associate with casein kinase 2, which results in the DNA-damage dependent phosphorylation and activation of p53. The FACT complex is a heterodimeric structure composed of Spt16 and SSRP1, both proteins evolutionarily conserved in eukaryotes. SSRP1 is a 87 Kd protein that binds DNA nonspecifically through a HMG1 domain located in the C-terminal and is overexpressed in breast cancer.
Although nuclear functions of FACT are well documented, little is known about the regulation of the complex. Recent works suggest that SSRP1 phosphorylation by CK2 alters its DNA-binding properties. During our studies attempting to understand the significance of this post-translational modification, we observed a reproducible decrease of SSRP1 levels after UV treatment. This prompted us to study SSRP1 turnover and elucidate the mechanism of SSRP1 degradation. Our findings suggest that SSRP1 is specifically cleaved by caspase 3 and 7 during the apoptotic cell death with further degradation of the resulting N-terminal fragment through the ubiquitin-proteasome pathway. I am currently studying in more details the effect of the cleavage of SSRP1 on FACT functions. In parallel, I launched a clinical study entitled “Assessment of the presence of SSRP1 apoptotic fragments in the serum of patients with Systemic Lupus Erythematus (SLE)”. The rationale for this study is that auto-antibodies against SSRP1 are highly prevalent in the blood of patients suffering from SLE, a disease tightly linked to apoptosis. We want through this study to connect the apoptotic cleavage of SSRP1 and the occurrence of auto-antibodies, which might lead to a better understanding of the etiology of the disease and the use of SSRP1 as a diagnostics tool.
Working in Dr. Lu’s lab has given me an excellent opportunity to work with a very talented group of people, in an environment that encourages the development of new skills.

Sept. 1996-June 1997: High School Teacher
Lycee Pierre de Fermat, Toulouse, France

I was in charge of the Biology courses  for two classes (10th and 11th grades) during the scholar year 1996/1997.

Education

Oct. 1998-Dec. 2002, Ph.D. Thesis: Transcriptional study of the early steps of the AcMNPV baculovirus infection and analysis of a cDNA library belonging to its host-cell, Sf9.
Laboratory: Dr Martine Cerutti, Laboratoire de Pathologie Comparee, INRA-CNRS-Universite Montpellier II, UMR 5087, 30380 St Christol les Ales, France.

The aim of my Ph.D. was to characterize the transcriptional events occurring during the early steps of the infection of insect cells by the baculovirus AcMNPV.
The first condition for successful baculoviral infection is the recruitment of the host transcription machinery to trigger the immediate early (IE) phase. Viral gene expression is then regulated in a cascade fashion, with IE, early (E) and late (L) phases. IE and E genes are transcribed under the control of the host RNA polymerase II whereas late promoters are controlled by a virally-encoded RNA polymerase. An interesting structural feature of most of the baculovirus genomes is the presence of interspersed small repeats, known as homologous regions (hrs). They act as enhancers for the RNA polII-mediated transcription of several viral early genes. The hr enhancer activity requires the binding of IE1, an immediate-early viral transcription activator, on 28-bp palindromic units. However, baculovirus hrs can stimulate transcription from exogenous and endogenous promoters in the absence of any viral transactivator, suggesting that the binding of host factors might be involved in the enhancer mechanism.
To investigate this possibility, we performed a comparative bioinformatics analysis of the genome of 25 baculoviruses and identified a large number of consensus binding sites for transcription factors of the b-Zip family, specifically enriched in the hrs. As baculoviruses genomes do not contain b-Zip protein genes, we tested and showed by EMSA that host proteins specifically bind these sites. Reporter assays further indicated that these sequences are able to activate a host promoter. Furthermore, they appear to play a role in the transactivation mediated by IE1, especially in the infected context.
In parallel, we developed a cDNA library from the host cell line, Sf9, in an attempt to identify some of the genes involved in this transactivation mechanism. Analysis of almost 6,000 ESTs from this library identified almost all the ribosomal protein genes. Bioinformatics analysis revealed features strikingly specific to insect or lepidoptera species such as insertions, low codon usage bias and unique protein signatures, an unexpected result given the high conservation of these genes throughout the evolution.
These works led to the publication of four papers, and I received my doctorate with the mention ‘with distinction’. 

Sept. 1997-Sept 1998, DEA (M.Sc. equivalent) in Parasitology: Characterization of a highly conserved satellite DNA from the parasitoid wasp Trichogramma brassicae.
Laboratory: Dr Flavie Vanlerberghe, Laboratoire de Biologie des Invertebres, INRA, Antibes, France.

My DEA research project was to develop a molecular method for the identification of Trichogramma brassicae, a minute parasitoid wasp used as a biological control agent against the maize corn borer, Ostrinia nubilalis. The genus Trichogramma consists of more than 150 species that are extremely difficult to distinguish morphologically, a problem that could be solved by molecular approaches. We identified a highly repeated satellite DNA from this species and demonstrated its suitability for identification purpose, with a good specificity and sensitivity by either squash blot or PCR.

1996: Agregation of Natural Sciences
French superior teaching diploma for High Schools and Universities
Laboratory techniques
•	Xenopus cell-free system : frogs priming, eggs collection, cell-free extracts preparation, replication assay, immunodepletion, compounds screening.
•	Protein expression and purification: in vitro, baculovirus and bacterial expression systems, transient assays (transfections) in insect and mammalian cells, tag-based purification (e.g. FLAG, HA, Myc and 6xHis), FPLC chromatography. 
•	Protein analysis : SDS-PAGE, coomassie, colloidal blue and silver staining, metabolic labelling (35S), western blot, immunofluorescence in situ.
•	Antibodies : generation, testing and purification of rabbit polyclonal and mouse monoclonal antibodies. 
•	Protein-protein and protein-DNA interactions: coimmunoprecipitation, EMSA, CAT and luciferase assays, in vivo ubiquitylation assays, chromatin immunoprecipitation assays.
•	DNA and RNA manipulation : extraction, cloning, sequencing, directed mutagenesis, end- and random-priming labelling (32P), southern blot, PCR, primer extension, RT-PCR, northern blot.
•	Libraries : construction of insect cDNA libraries (in phage ), screening (cDNA and expression), conversion into bacterial clones for large-scale sequencing (http://bioweb.ensam.inra.fr/spodobase/).
•	Bioinformatics: PCR tools (macVector, Primer3), general genes and proteins databases (GenBank, Swiss-Prot, UCSC), comparisons and alignments (BLAST, ClustalW), phylogeny (Clustal, Treeview).

Career development

Awards
•	Eli Lilly-AACR Scholar-in-training travel award, AACR-NCI-EORTC International Conference, October 2007, San Francisco, USA.
•	American Society of Virology travel award, Annual Meeting of the American Society of Virology,  July 2001, Madison, USA.

Grants
•	NIH-NRSA Cancer Biology Training grant (July 2006-June 2008).

Publications

•	Landais I, Sobeck A, Stone S, LaChapelle A, Hoatlin MEH (submitted) A novel cell-free screen for small molecule inhibitors of the Fanconi anemia/BRCA pathway.
•	Landais I, Li Y, Kumari A, Lu H (in revision) SSRP1 recruitment to genes undergoing transcription depends on the DNA-binding activity of its HMG-1 box.
•	Li Y, Zeng SX, Landais I, Lu H (2007) Human SSRP1 has Spt16-dependent and independent roles in gene transcription. J Biol Chem 282: 6936-45
•	Landais I, Lee H, Lu H (2006) Coupling caspase cleavage and ubiquitin-proteasome-dependent degradation of SSRP1 during apoptosis. Cell Death Differ 13: 1866-78
•	Landais I, Vincent R, Bouton M, Devauchelle G, Duonor-Cerutti M, Ogliastro M (2006) Functional analysis of evolutionary conserved clustering of bZIP binding sites in the baculovirus homologous regions (hrs) suggests a cooperativity between host and viral transcription factors. Virology 344: 421-31.
•	Serrano-Pinto V, Landais I, Ogliastro MH, Gutierrez-Ayala M, Mejia-Ruiz H, Villarreal-Colmenares H, Garcia-Gasca A, Vazquez-Boucard C (2004) Vitellogenin mRNA expression in Cherax quadricarinatus during secondary vitellogenic at first maturation females. Mol Reprod Dev 69: 17-21.
•	Landais I, Ogliastro M, Mita K, Nohata J, Lopez-Ferber M, Duonor-Cerutti M, Shimada T, Fournier P, Devauchelle G. (2003) Annotation pattern of ESTs from Spodoptera frugiperda Sf9 cells and analysis of the ribosomal protein genes reveal insect-specific features and unexpectedly low codon usage bias. Bioinformatics 19: 2343-50. 
•	Volkoff AN, Rocher J, d'Alencon E, Bouton M, Landais I, Quesada-Moraga E, Vey A, Fournier P, Mita K, Devauchelle G (2003) Characterization and transcriptional profiles of three Spodoptera frugiperda genes encoding cysteine-rich peptides. A new class of defensin-like genes from lepidopteran insects? Gene 319: 43-53. 
•	Landais I, Pommet J, Mita K, Nohata J, Gimenez S, Fournier P, Devauchelle G, Duonor-Cerutti M, Ogliastro M (2001) Characterization of the cDNA encoding the 90 kDa heat-shock protein in the Lepidoptera Bombyx mori and Spodoptera frugiperda. Gene 271: 223-31. 
•	Landais I, Chavigny P, Castagnone C, Pizzol J, Abad P, Vanlerberghe-Masutti F (2000) Characterization of a highly conserved satellite DNA from the parasitoid wasp Trichogramma brassicae. Gene 255: 65-73.

International meetings
•	Landais I, Sobeck A, Stone S, LaChapelle A, Padhye S, Snyder J, Hoatlin ME. A novel cell-free screen for drugs that modulate the human Fanconi/breast cancer susceptibility protein network. Poster, AACR-NCI-EORTC Molecular targets and Cancer Therapeutics International Conference, October 2007, San Francisco, USA
•	Landais I, Sobeck A, Stone S, LaChapelle A, Padhye S, Snyder J, Hoatlin ME. A Xenopus cell-free assay for screening of compounds that modulate the Fanconi anemia pathway. Poster, Fanconi anemia Research Fund Meeting, October 2007, Chicago, USA
•	Landais I, Vincent R, Robert L, Galibert L, Devauchelle G, Duonor-Cerutti M, Ogliastro M. Cooperativity between the baculovirus IE1 transcription factor and host CRE-like binding factors to activate hr5-dependent transcription. Oral presentation, Annual Meeting of the American Society of Virology, July 2001, Madison, USA.
•	Landais I, Pommet JM, Mita K, Nohata J, Gimenez S, Fournier P, Devauchelle G, Duonor-Cerutti M, Ogliastro M. Characterization of the cDNA encoding the 90 kDa heat-shock protein in the Lepidoptera Bombyx mori and Spodoptera frugiperda. Oral presentation, Fifth International Workshop on Molecular Biology and Genetics of the Lepidoptera, August 2001, Kolympari, Greece.
•	Landais I, Mita K, Nohata J, Gimenez S, Ogliastro M, Duonor-Cerutti M, Feyereisen R, Lopez-Ferber M, Devauchelle G, Fournier P. Spodoptera frugiperda gene expression analysis using EST. Poster, Fifth International Workshop on Molecular Biology and Genetics of the Lepidoptera, August 2001, Kolympari, Greece.

Additional teaching experiences
•	Molecular Biology classes at the French Institute of Agronomy (INRA)	2002
•	Supervision of a graduate student (V. Serrano-Pinto, publication # 3)	2001
References

•	Maureen E. Hoatlin, PhD (PI, OHSU, USA)
hoatlinm@ohsu.edu, phone : +1 503 494 1123
•	Hua Lu, MD-PhD (PI, OHSU, USA)
luh@ohsu.edu, phone : +1 503 494 7414	
•	Philippe Fournier, PhD (Director, INRA, France)
fourniep@ensam.inra.fr, phone : +33 4 67 14 41 13
•	Gérard Devauchelle, PhD (Director, CNRS, France) 
gerard.devauchelle@cpbs.univ-montp1.fr, phone : +33 4 66 78 37 03