Dr. Gilbert J. Cote
The University of Texas M. D. Anderson Cancer Center
Department of Endocrine Neoplasia
- Regulation of RNA processing
- RNA splicing and cancer
- Familial endocrine neoplasia
The path from gene transcription to protein translation involves several key steps. Chief among them is the processing of precursor RNA to its mature translatable mRNA. Our research group maintains a keen interest in the mechanisms of RNA splicing responsible for accurate exon recognition. Alterations of the normal processing pathway result from either mutation of processing signals in individual genes or changes in the factors that regulate splicing decisions. We currently employ model systems that examine both mechanisms. One example is the processing pathway for fibroblast growth factor receptor (FGFR) RNA precursor. This receptor is a key regulator of cell growth, differentiation, and apoptosis. FGFR RNA transcripts produce multiple receptors that differ in ligand-binding affinity. In astrocytic brain tumors, the processing is aberrantly altered to produce only mRNA encoding, the high-affinity receptor form. We identified the RNA splicing factor polypyrimidine tract-binding protein (PTB) as a potential tumor-specific regulator of FGFR splicing. We also study genome-wide RNA splicing and expression of splicing regulators using new microarray technologies. Our goal is to uncover links between splicing factor misexpression and aberrant splicing in cancer. These studies have identified several potential downstream targets of splicing factors like PTB that may function in brain tumor cell growth and invasion.
A second major focus of our laboratory is the study of the genetic mechanisms involved in familial endocrine neoplasias. Specific examples include mutations of the RET proto-oncogene in patients with multiple endocrine neoplasia (type 2) and mutations of the MEN1 gene in patients with multiple endocrine neoplasia (type 1). More recently we have used array-based approaches to study gene copy number and expression. Our experience with genetic analysis of these disorders has allowed a better understanding of disease progression and created the opportunity for the application of genetic diagnosis and treatment. These translational studies are performed in close collaboration with faculty within the Endocrine Center.
A tutorial in my laboratory would provide experience in a variety of molecular biology and genetic techniques including: bioinformatic analysis of splicing, mammalian cell transfection, RNA-PCR, Western blots, DNA mutation analysis, and cellular assays for transformation.
Program in Human and Molecular Genetics
Office: MDA FCT12.5024 (Unit 1461)
Ph.D. - University of Vermont - 1987