HEAD of the Laboratory
Vladimir V. Strelnikov
Dmitry V. Zaletaev, chief research scientist, Doctor of Biology, Professor.
Marina V. Nemtsova, chief research scientist, Doctor of Biology, Professor.
Tatyana V. Kekeeva, leading research scientist, PhD
Aleksandr S. Tanas , leading research scientist, PhD
Ekaterina B. Kuznetsova, senior research scientist, PhD
Ekaterina A. Alekseeva, research scientist, PhD
Kirill I. Anoshkin, research scientist
Ilya V. Volodin, research scientist
Kristina O. Karandasheva, research scientist
Galina G. Chesnokova, research scientist
CONTACTS: (499) 612-00-19
Back in 1993, the Clinical Cytogenetics Laboratory gave birth to a group of co-workers who initiated the development of molecular genetic approaches towards Prader-Willi, Angelman and fragile X syndromes diagnostics with the financial support from the Russian Human Genome Program. They also paid much attention to research of the microdeletion syndromes, molecular genetic characterization of the shortest regions of deletion overlaps, mapping of the tricho-rhino-phalangeal syndromes and multiple exostoses disease. In 1999, the group initiated research in epigenetic pathology in cancer, as well as the development of the diagnostic procedures for inherited forms of cancer (retinoblastoma, Wilms tumor-aniridia, multiple endocrine neoplasia). Professor Dmitri V. Zaletaev, DSci, became the founder of this group and then the Head of the first Epigenetic Laboratory in Russia.
Main fields of research
At present, molecular basis of hereditary pathology is the most intensively studied problem in medical and molecular genetics. Recent achievements in this field of science demonstrate that unraveling the nucleotide sequences is no more than one of the first steps towards understanding the natural laws of functioning of the genome as a whole. Studies of normal and abnormal structural and functional characteristics of chromosome regions, DNA modifications and functions of “gene concerts” become one of leading fields of research.
Imprinting phenomenon, position effect and structural and functional chromatin organization within the specific chromosome region predetermine the patterns of gene expression. Changes in gene expression without structural alterations in its nucleotide sequence are classified as epigenetic ones. Mechanisms of these disorders include abnormal methylation of promoter and regulatory regions of genes, dynamic (amplification of microsatellite repeats) and point mutations in the regulatory regions, transpositions of repetitive genomic elements. The contribution of epigenetic regulation of gene activity based on the abnormal methylation of promoter CpG islands leading to their inactivation has been considered recently one of causes of a number of genetic diseases and cancer.
One of the main fields of research in the Laboratory includes studies of structural and functional organization of the chromosome regions whose alterations lead to syndromic forms of multiple congenital defects. Special attention is paid to microdeletion syndromes and diseases associated with imprinting and dynamic mutations. Characterization of the range of molecular pathology and development of the diagnostic protocols is carried out in this field.
Another field of research is related to molecular mechanisms of carcinogenesis and, first of all, assessment of epigenetic mechanisms of gene expression regulation. Most attention is paid to the search for and characterization of molecular markers with potential diagnostic and prognostic relevance. We consider several principal aspects: molecular diagnostics of hereditary forms of cancer, identification and characterization of poor prognostic markers, micrometastases diagnostics, search for and characterization of carcinogenesis markers detectable presymptomatically. Diagnostic protocols allowing improvements in diagnostic quality and treatment efficiency are the main results of this research. Studies of stromal-mesenchymal interactions, clonal origin of tumors and their relapses are carried out within this field of research.
The third field of the research is related to the analysis of polymorphic DNA variants that increase the risk of wide-spread diseases including cancers. Besides, studies of DNA polymorphisms that determine the effects of medications are also carried out. Results of these studies may and can improve the quality of life and public health.
The search for genetic causes of male and female infertility, in particular, characterization of polymorphic DNA variants complicating pregnancy, characterization of nonrandom X chromosome inactivation, etc. os one more field of research. Studies of aneuploidies and epigenetic abnormalities are carried out at the early stages of development (pre-blastocyst) of embryos and in cases of early pregnancy losses.