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Dr. Oleg Evgrafov
Professor of Cell Biology
Developing Biological Models to Study the Genetic Etiology of Schizophrenia
Schizophrenia has a heritability as high as 80% making it a genetic disease tha believed
to be influenced by environmental factors. Mechanisms of the disease are defined by
genetic variants, which are translated into phenotype through multiple genetic, molecular
and cellular processes. Most of schizophrenia heritability is explained by common
single nucleotide polymorphisms (SNPs). Currently, over 250 schizophrenia-associated
loci have been identified but future genomic studies are needed to help us better
understand the etiology of the disease. Genome-wide association study (GWAS) data
suggest that most genetic variants involved in schizophrenia etiology act through
altering gene expression; thus, expression profiling in appropriate biological models,
such as the one under development at SUNY Downstate by Dr. Oleg Evgrafov, professor
of cell biology and member of the Institute for Genomic Health, has the potential
to become a centerpiece of genetic studies of schizophrenia to link GWAS, epigenetic,
gene expression and cell function studies and model mechanisms of the disease.
Dr. Evgrafov, working closely with Dr. James Knowles and Drs Carlos and Michele Pato,
is developing a cellular model to elucidate the neurodevelopmental aspects of schizophrenia.
Nasal biopsies on individuals with schizophrenia and control subjects recruited from
the NIH-supported Genomic Psychiatry Cohort study have enabled Dr. Evgrafov to establish
cell lines from individuals with schizophrenia and control subjects. These olfactory
neuroepithelium cell lines, which continue to be derived from eligible research subjects,
are being used to elucidate the neurodevelopmental aspects of schizophrenia. This
translational research, beginning at the bench in laboratories at Downstate, holds
great promise for identifying “missing links” in the schizophrenia disease mechanisms
by enabling researchers to find associations and underlying molecular processes between
genome and gene expression, gene expression and cellular functions and cellular functions
and phenotype (diagnosis).
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