Project Summary

Vladimir Vladimirov, M.D., Ph.D. (Young Investigator 2006) of Virginia Commonwealth University, will analyze the possible interaction between the dystrobrevin binding protein 1 (DTNBDI) risk haplotype and the AKTl signaling pathway in schizophrenia. Three high-risk haplotypes in DTNBD1 are associated with schizophrenia, including one in Irish samples that Dr. Vladimirov studies. The AKTl signaling pathway is involved in the regulation of neuronal survival inhibition of both cell-cycle arrest and apoptosis. The overexpression of DTNBDl has been associated with increased phosphorylation and activation of AKT1. In a preliminary study, Dr. Vladimirov evaluated the differences between cases and controls in the expression of 14 critical loci in the AKTl signaling pathway. He found that expression of p53, p21 and p27, genes involved in the cell cycle arrest, was significantly downregulated. Dr. Vladimirov will reevaluate the mRNA expression of this set of loci in his Irish sample, in which the clinical status and DTNBD1 haplotype structure are defined, allowing him to identify expression changes attributable to DTNBDl haplotypes and to clinical status. Since mRNA and protein level are often uncorrelated, and much critical protein regulation is due to control of activation, he also will test for changes in these molecules at total protein level and phosphorylation status

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

Search Again