I received my undergraduate education at the Moscow Institute of Physics and Technology, graduating in 1987. I have mastered molecular biological and biochemical techniques working one year at the Student Center of the Shemyakin's Institute of Bioorganic Chemistry. My M.S. thesis was carried out in the lab of professor N.N. Modyanov. After one year of working as a research Associate in the professor Modyanov's lab I immigrated with my family to the United States.
In USA, Dr. Joseph M. Ahearn at Johns Hopkins University hired me as a technician. After one year of working there we have published a paper and I entered the Graduate Program in Biochemistry, Cellular and Molecular Biology at Johns Hopkins University, School of Medicine. My rotation project in Daniel Nathans laboratory was to identify peptide with in vivo phosphorylation sites of JunB protein by its phosphopeptide analysis.
I received my Ph.D. under Dr. Jeffry L. Corden, studying the function of the C-terminal domain (CTD) of eukaryotic RNA-polymerase II. My Ph.D. thesis consists of two parts. First, I used yeast genetics to study CTD phosphorylation site suppressor mutants. I have shown that two different phosphorylation sites on the CTD can be genetically distinguished by suppression analysis. As a second project I used the two-hybrid method to clone genes encoding proteins that interact with the CTD. The bioinformatics analysis of CTD interacting proteins yielded a discovery of novel splicing-related proteins interacting with RNA polymerase II. The discovery of these proteins suggested the existence of the physical link between transcription and splicing as well as a novel mechanism of gene expression regulation.
I have accomplished my postdoctoral training at Novartis Corporation where I investigated the functional differences between Raf kinase isoforms. I have identified several novel human proteins some of which interact specifically only with one Raf isoform. Two A-Raf specific proteins showed significant sequence similarity to mitochondrial protein import receptors from lower eukaryots by bioinformatics analysis. To further validate the biological relevance of these interactions I showed that A-Raf but not C-Raf protein is concentrated in the rat liver mitochondria. I also found a novel protein kinase interacting with all Raf isoforms. Its bioinformatics analysis revealed that it is most homologous to dual specificity serine/threonine/tyrosine kinases. I have expressed new kinase in E.coli, purified it to homogeneity for further biochemical characterization and X-ray crystallography. In addition I have helped my supervisor Dr. Lawrence P. Wennogle in starting the protein tyrosine phosphatase project by cloning eight protein phosphatases. The goal of this project was to find protein tyrosine phosphatase inhibitors that block insulin-receptor dephosphorylation and can be used as therapeutic drugs in type II diabetes. For my extracurricular activity I have actively participated in the "Antisense in Restenosis" project. As part of this effort I have supervised two technicians and trained them in Molecular Biological techniques.
I was working as a project team leader at deCODE Genetics Inc for one year. My group developed a new strategy to find mutations in the genomic loci mapped by linkage analysis in human genome. The technology includes amplification of large genomic fragments by long and accurate PCR, their subcloning, high throughput sequencing and data analysis using proprietary software. We have successfully amplified and cloned about 400 Kb of human major histocompatibility region from chromosome 6 from 8 individuals in order to search for the mutations associated with various disease.
InforMax Inc has hired me to develop new software for Genetic Analysis. The software was part the GenoMax, the enterprise-wide bioinformatics software package developed by InforMax. The module that was designed by me and developed together with three programmers allows storage and management of the genotyping and phenotypic data, phenotypic analysis and classification, and three classes of genetic analysis. Association studies included allele frequencies and penetrance calculations, linkage disequilibrium analysis included haplotype-relative risk method, several different transmission disequilibrium tests, pedigree linkage analysis was offered through seamless integration of GeneHunter and SimWalk2 public software packages. The software architecture of the Genetic Analysis module is similar to the GenoMax architecture. It consists of Java user interface, ORACLE database and C/C++ cgi-like middle layer, which also run algorithmic programs.
In addition to software for Genetic Analysis I have designed algorithms for multiplex PCR primer design and long PCR primer design. This work was done in collaboration with Viatcheslav Gorelenkov, who did the coding and also some algorithm design. We have also improved and significantly accelerated existing algorithms for PCR primer design and incorporated the use of molecule annotation into primer design. All PCR primer design improvements have been included into VectorNTI suite v.7.0 and 8.0. VectorNTI is a personal software package for bioinformatics produced by InforMax.