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One or more keywords matched the following properties of Rogaev, Evgeny

Academic Background


Moscow State University, Biological Department, School of Genetics

Master D. 1983
Ph.D. 1988
Dr.Sci. 1996

Work History

Scientific Researcher, Leading Researcher
National Mental Research Center
Russian Academy of Medical Science
Visiting Scientist, Visiting Professor (U of Toronto) 1992-1995, 2001
Head, Laboratory of Molecular Brain Genetics
Research Center of Mental Health
Russian Academy of Medical Sciences
1990- present
Professor of Psychiatry, BNRI, UMASS Medical School 2002- present

Molecular genetic mechanisms of neuropsychiatric diseases and dementia
Mapping and Positional cloning of genes for human pathologies

Photo: Evgeny Rogaev, PhD, DrSciOur research is focused on the identification of genes and cellular proteins that play a critical role in normal and pathological aspects of human behavior. To identify such genes and proteins we first use the strategies of linkage, genetic association analysis and positional cloning to isolate the mutant or polymorphic genes underlying the human diseases. We then develop functional assays to express these genes in vitro and in vivo to study their normal and pathogenic functions.

We are interested also in the study of evolutionary aspects of human populations, genome and specific genes in order to elucidate the phenomenon of some behavioral disorders prevalent in humankind.

Alzheimer's disease, schizophrenia and depression are three of the most common mental disorders and our primary interest.

Alzheimer's Disease

The mutations in human presenilin 1 and presenilin 2 genes, which we and our colleagues described previously, are a major cause of familial early-onset Alzheimer's disease. The AD-mutations in the presenilins are supposed to enhance its proteolysis-associated activity, that in turn may result in elevated amyloid precursor protein cleavage and production of neurotoxic beta amyloid derivates. However, other "non-amyloid" mechanisms of pathogenic effects of presenilins have not yet been ruled out. The role of presenilins in most common "non-familial" AD cases, and cellular factors or chemical compounds which may modulate the activity of presenilins, are still unclear. Our studies search for factors that may regulate presenilin genes and interact with presenilin proteins. We search for population variations and modifications in promoters of presenilin 1 and presenilin 2 genes and measure the transcriptional activity of variable regulatory regions of presenilins. The potential exogenous and endogenous inhibitors or repressors of these elements are tested in neural human or rat cells. We also search for families of proteins that interact directly with presenilins or their targets (e.g., Amyloid Precursor Protein and Notch-receptors) and which may serve as modulators of presenilin mediated proteolysis. These studies will contribute to understanding of fundamental mechanisms of inter- and intra-cellular signaling and also provide potential targets for treatment of Alzheimer's disease neuro-degeneration.

More than 50% of AD have no association with mutations in encoding regions of presenilins and other known AD -genes (ApoE,APP). Thus, there must be other AD genes yet to be discovered. In order to identify such genes, we combine the methods of genetic association and linkage analysis in families and population groups of late-onset AD patients and age-matched non-demented individuals. We test the single nucleotide polymorphisms (SNPs) in several selected chromosomal loci to define the narrow genomic region and ultimately identify novel genes associated with AD.

Schizophrenia and Depression

The molecular-genetic mechanisms and genes for schizophrenia or affective disorders remains to be elusive. We are collecting large samples of schizophrenia and affective disorders from ethnically defined populations. The identification of specific SNPs haplotypes and linkage disequilibrium analysis for a few candidate loci and genes are currently of our particular interest. A MassARRAY MALDI system will be used for fine mapping of these loci. Recently two novel candidate-genes for schizophrenia have been isolated from two chromosomal loci by testing of multiple polymorphic markers in two population samples. These primary data are to be replicated in the genetic study of other population samples. To elucidate the biological significance of the candidate-genes found by genetic approach, the study of effects of up- and down regulation of the candidate- genes on neuroplasticity and neurotransmition signaling will be undertaken.

Other Diseases

It is assumed that common diseases represent mainly polygenic or multifactorial diseases. The identification of the susceptible genes for such diseases is rather complicated. However, familial (Mendelian) transmission of diseases which may be clinically similar to common phenotypes is observed in rare families. We are interested in identifying and studying such families. Isolation of the disease genes in these rare families may help to elucidate the molecular mechanisms for more common forms of the human diseases.

We use unique resources in several genetic isolates and limited human populations. Large pedigrees of human families with autosomal-dominant and autosomal-recessive diseases with unknown gene defects are being collected . Currently, we apply strategies of positional cloning and direct screening of candidate-genes for variety of human diseases, including eg., morbid obesity with hyperphagia, a specific case of premature aging, eye-diseases, alopecia (baldness) and others.

One or more keywords matched the following items that are connected to Rogaev, Evgeny
Item TypeName
Academic Article Failure to detect missense mutations in the S182 gene in a series of late-onset Alzheimer's disease cases.
Academic Article Analysis of the 5' sequence, genomic structure, and alternative splicing of the presenilin-1 gene (PSEN1) associated with early onset Alzheimer disease.
Academic Article Presenilin polymorphisms in Alzheimer's disease.
Academic Article Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant.
Academic Article Cloning and characterization of the Drosophila presenilin homologue.
Academic Article [Presenilins: detection and characterization of Alzheimer's disease genes].
Academic Article Novel class of polytopic proteins with domains associated with putative protease activity.
Academic Article Effects of human presenilin 1 isoforms on proliferation and survival of rat pheochromocytoma cell line PC12.
Academic Article Impas 1 possesses endoproteolytic activity against multipass membrane protein substrate cleaving the presenilin 1 holoprotein.
Academic Article The Caenorhabditis elegans IMPAS gene, imp-2, is essential for development and is functionally distinct from related presenilins.
Academic Article [Genetic factors and a polygenic model of Alzheimer's disease].
Academic Article Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing.
Academic Article Presenilin-2 (PS2) expression up-regulation in a model of retinopathy of prematurity and pathoangiogenesis.
Academic Article Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations.
Academic Article Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.
Academic Article Missense mutation of S182 gene in Italian families with early-onset Alzheimer's disease.
Academic Article [Molecular basics of Alzheimer's disease].
Academic Article Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene.
Concept Presenilins
Concept Presenilin-2
Concept Presenilin-1
Academic Article Different Pathways to Neurodegeneration.
Academic Article Immunogenetic Factors of Neurodegenerative Diseases: The Role of HLA Class II.
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  • Presenilins