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OVERVIEW OF RESEARCH PROGRAM

The aim of our research program is to create and use tools for computational genomics in order to identify susceptibility genes and therapeutic targets for complex diseases. Specifically, we are developing software, designing databases, and use sophisticated computational methods for combined analyses of genome sequences and gene expression data. In close collaboration with basic and clinical research partners we are focusing on microarray informatics and its application to obesity and cancer.


MICROARRAY INFORMATICS

We are developing an integrated system for storing and analyzing microarray data. The analytical pipeline includes modules for image processing, cluster analysis, sequence analysis as well as tools for storing and retrieving microarray data. We are using the object model for representing microarray data developed by the EBI (www.ebi.ac.uk/arrayexpress) which supports MIAME requirements. The data model has been implemented in Oracle and a data loader from the MAML file format (an XML based format developed by MGED) is in development. An application server based on the image processing and cluster analysis tools is also in development. According to our licensing policy, the tools are available free of charge to academic, government, and other nonprofit institutions for noncommercial, nonprofit internal research purposes.


OBESITY

Our aim is to delineate transcriptional regulatory networks of adipocyte differentiation controlled by PPARs. For this purpose advantage is taken of the availability of cellular model systems, the specificity provided by synthetic ligands, and the cDNA microarray technology. We first generated hypotheses by identifying in silico putative PPAR target genes. In collaboration with The Institute for Genomic Research (TIGR), Rockville, MD/USA (PI: J. Quackenbush) we then designed microarrays enriched with these candidate genes. The focused microarrays are used to monitor gene expression profiles during adipocyte differentiation of 3T3-L1 cell lines.


CANCER

Our aim is to identify molecular signatures in T-cells in cancer. To identify genes up- or downregulated in the tumor microenvironment, we are developing a reference database of expression profiles corresponding to various treatments of Jurkat cells. The database will be used to identify gene expression patterns in anergic T-cells and tumor micro-environment T-cells sampled from patients with cancer. Using a database of reference profiles, the pathway(s) perturbed by the communication between tumor and immune cells would be ascertained by asking which expression patterns in the database its profile most strongly resembles. We will take advantage of the availability of cell lines and microarrays for large-scale gene expression profiling. This project is a collaboration with the INSERM Unit 255, Paris, France (PI: Jerome Galon).