Andrew Chess completed his M.D. degree at Columbia College of Physicians and Surgeons and postdoctoral training with Dr. Richard Axel at Columbia. Prior to joining CHGR, Chess was a faculty member in the MIT biology department and the Whitehead Institute. He joined the CHGR in 2004 and moved his laboratory to MGH upon the opening of CHGR in 2005.
Chess has a longstanding interest in studying gene regulatory mechanisms underlying the specification of individual cell type in the nervous and immune systems. Two central areas in the lab are studies of gene families subject to monoallelic expression and studies of alternative splicing as a mechanism for generating unique cell identity.
The Chess lab has played a central role in defining a class of autosomal genes with properties similar to X-inactivation. Taking advantage of the fact that monoallelically expressed genes replicate asynchronously, they discovered that the replication timing of these genes is coordinated at a whole-chromosome level. Thus, there is a randomly determined non-equivalence between the maternal and paternal copy of each autosome. The Chess group uses molecular biology, microarray technology and informatics to dissect underlying mechanisms of monoallelic expression and chromosome-pair non-equivalence.
The Drosophila Dscam (Down syndrome cell adhesion molecule) gene is essential for axon guidance and has over 38,000 possible alternative splice forms. This extraordinary diversity (encoding immunoglobulin domains) can potentially be used to distinguish cells. Using a custom made microarray we found that each cell type expresses a broad, yet distinctive spectrum of Dscam isoforms. Critical single cell RT-PCR experiments then showed that individual cells express ~15-50 distinct mRNAs. Thus, each individual cell’s Dscam repertoire is different from those of its neighbors, providing a potential mechanism for the generation of unique cell identity in the nervous system and elsewhere. We are also investigating mammalian genes whose alterative splicing might be used to similarly generate diversity.
|
