Yuri B. Lebedev

Personal information

Being laboratory head, Yuri Lebedev proceeds with his research on interaction of retroelements and primate genome and evolves his efforts in related fields of functional genomics. Dr. Lebedev is the first (or leading) author of over 60 articles and reviews. In addition to basic research he carries out education of students as a permanent speaker at schools for young scientists as well as a supervisor of student’s projects. During the last 10 years, under Dr. Lebedev supervision over 20 masters of sciences together with 7 PhDs have been graduated from his group.

Education

PeriodCountry, cityEducation institutionAdditional info
1973–1978 Moscow Moscow state university

Scientific interests

Dr. Lebedev is one of the leading Russian scientists working in the field of mammalian genome structure, functioning and evolution. He started research in the field in the early nineties. Since establishing Russian State program “Human Genome”, Dr. Lebedev with other young scientists from Eugene Sverdlov’s lab joined the program among the first participants. In these years Yuri Lebedev’s research was focused on functional mapping of distinct human chromosomes.

Awards & honors

Dr. Lebedev became the winner of A.A. Baev prize rewarded “for series of research on high-resolution mapping of transcribed and regulatory sequences on Chr19” in 1997.

Main scientific results

Being presented at several HUGO Meetings, Dr. Lebedev’s results attracted a high interest of the specialists. As a part of his work on functional mapping of human chromosome 19, Dr. Lebedev published his first articles on the problem of HERV LTR’s impact on human genome evolution. Dr. Lebedev elaborated a concept of involvement of retroelement mobility in primate speciation. According to this theory retroposition of multiple regulatory sequences could result in essential modulations of gene expression systems. The first experimental genome-wide comparison of retroelement distribution in human and chimpanzee genome was performed under Dr. Lebedev’s supervision. The results of the project confirmed main postulates of Lebedev’s concept and led to discovery of representative groups of retroelements that present exclusively in human genome. Newly developed approach to mammalian genomes comparison and discovering of human specific retroelements were selected for annual issues of “The most important achievements of Russian Academy of Sciences” in 2001—2003 years. At the end of 2004, Dr. Lebedev defended his doctoral thesis entitled “Human endogenous retroviruses: structural-evolutionary analysis”.

Scientific societies’ membership

Dr. Lebedev became HUGO member in 1996.

Selected publications

  1. Shagina I., Bogdanova E., Mamedov I., Lebedev Y., Lukyanov S., Shagin D. (2010). Normalization of genomic DNA using duplex-specific nuclease. BioTechniques 48 (6), 351–355 [+]

    An application of duplex-specific nuclease (DSN) normalization technology to whole-genome shotgun sequencing of genomes with a large proportion of repetitive DNA is described. The method uses a thermostable DSN from the Kamchatka crab that specifically hydrolyzes dsDNA. In model experiments on human genomic DNA, we demonstrated that DSN normalization of double-stranded DNA formed during C0t analysis is effective against abundant repetitive sequences with high sequence identity, while retaining highly divergent repeats and coding regions at baseline levels. Thus, DSN normalization applied to C0t analysis can be used to eliminate evolutionarily young repetitive elements from genomic DNA before sequencing, and should prove invaluable in studies of large eukaryotic genomes, such as those of higher plants.

  2. Mamedov I.Z., Shagina I.A., Kurnikova M.A., Novozhilov S.N., Shagin D.A., Lebedev Y.B. (2010). A new set of markers for human identification based on 32 polymorphic Alu insertions. EJHG , [+]

    A number of genetic systems for human genetic identification based on short tandem repeats or single nucleotide polymorphisms are widely used for crime detection, kinship studies and in analysis of victims of mass disasters. Here, we have developed a new set of 32 molecular genetic markers for human genetic identification based on polymorphic retroelement insertions. Allele frequencies were determined in a group of 90 unrelated individuals from four genetically distant populations of the Russian Federation. The mean match probability and probability of paternal exclusion, calculated based on population data, were 5.53 x 10(-14) and 99.784%, respectively. The developed system is cheap and easy to use as compared to all previously published methods. The application of fluorescence-based methods for allele discrimination allows to use the human genetic identification set in automatic and high-throughput formats.European Journal of Human Genetics advance online publication, 24 February 2010; doi:10.1038/ejhg.2010.22.

  3. Mamedov I.Z., Britanova O.V., Chkalina A.V., Staroverov D.B., Amosova A.L., Mishin A.S., Kurnikova M.A., Zvyagin I.V., Mutovina Z.Y., Gordeev A.V., Khaidukov S.V., Sharonov G.V., Shagin D.A., Chudakov D.M., Lebedev Y.B. (2009). Individual characterization of stably expanded T cell clones in ankylosing spondylitis patients. Autoimmunity 42 (6), 525–36 [+]

    Ankylosing spondylitis (AS) is commonly characterized by clonal expansions of T cells. However, these clonal populations are poorly studied and their role in disease initiation and progression remains unclear. Here, we performed mass sequencing of TCR V beta libraries to search for the expanded T cell clones for two AS patients. A number of clones comprising more than 5% of the corresponding TCR V beta family were identified in both patients. For the first time, expanded clones were shown to be stably abundant in blood samples of AS patients for the prolonged period (1.5 and 2.5 years for two patients, correspondingly). These clones were individually characterized in respect to their differentiation status using fluorescent cell sorting with CD27, CD28, and CD45RA markers followed by quantitative identification of each clone within corresponding fraction using real time PCR analysis. Stable clones differed in phenotype and several were shown to belong to the proinflammatory CD27 - /CD28 - population. Their potentially cytotoxic status was confirmed by staining with perforin-specific antibodies. Search for the TCR V beta CRD3 sequences homologous to the identified clones revealed close matches with the previously reported T cell clones from AS and reactive arthritis patients, thus supporting their role in the disease and proposing consensus TCR V beta CDR3 motifs for AS. Interestingly, these motifs were also found to have homology with earlier reported virus-specific CDR3 variants, indicating that viral infections could play role in development of AS.

  4. Chkalina A.V., Zviagin I.V., Mamedov I.Z., Britanova O.V., Staroverov D.B., Lebedev Iu.B. (2009). [The oligoclonal expansion of T cells: study of its stability over time]. Bioorg. Khim. 36 (2), 206–14 [+]

    A novel experimental approach to the investigation of the repertoire of peripheral T lymphocytes of patients suffering from ankylosing spondylitis (AS) is proposed. This approach is based on the wide-range sequencing of cDNA of the beta-chain of the T-cellular receptor (TcR). The results of the analysis of the diversity of sequences of the TcR antigen-binding domain (CDR3) inside the total pool of one patient with AS are presented by the example of the second V family (BV2) of TcR. The expansion of six independent TcR-expressing clones of T cells with a similar amino acid sequence of the CDR3 domains was proposed based on the results of the comparative structural analysis of the clone libraries of the cDNA of TcR BV2. The long-time stable expansion of these T clones was demonstrated during the development of the disease by specific monitoring.

  5. Lebedev Y.B., Amosova A.L., Mamedov I.Z., Fisunov G.Y., Sverdlov E.D. (2007). Most recent AluY insertions in human gene introns reduce the content of the primary transcripts in a cell type specific manner. Gene 390 (1-2), 122–9 [+]

    New strategy for large-scale functional analysis of polymorphic retroelements is described. Inhibitory effect of dimorphic Alu on human gene expression was discovered. Cell type specificity of the inhibitory effect was observed in heterozygous cell lines.

  6. Mamedov I.Z., Arzumanyan E.S., Amosova A.L., Lebedev Y.B., Sverdlov E.D. (2005). Whole-genome experimental identification of insertion/deletion polymorphisms of interspersed repeats by a new general approach. Nucleic Acids Res. 33 (2), e16 [+]

    A new experimental technique for genome-wide detection of integration sites of polymorphic retroelements (REs) is described. Efficiency of the technique was demonstrated by discovering large subset of dimorphic AluY elements undetectable by available bioinformatic approaches.

  7. Buzdin A., Ustyugova S., Gogvadze E., Lebedev Y., Hunsmann G., Sverdlov E. (2003). Genome-wide targeted search for human specific and polymorphic L1 integrations. Hum. Genet. 112 (5-6), 527–33 [+]

    An efficient application of original method of subtractive genomic DNA hybridization to identification of species-specific LINE insertions.

  8. Buzdin A., Ustyugova S., Khodosevich K., Mamedov I., Lebedev Y., Hunsmann G., Sverdlov E. (2003). Human-specific subfamilies of HERV-K (HML-2) long terminal repeats: three master genes were active simultaneously during branching of hominoid lineages. Genomics 81 (2), 149–56 [+]

    Complete structural analysis of human specific LTRs. Multiple endogenous retroviral retropositions in course of human speciation were confirmed at the very first time.

  9. Mamedov I., Batrak A., Buzdin A., Arzumanyan E., Lebedev Y., Sverdlov E.D. (2002). Genome-wide comparison of differences in the integration sites of interspersed repeats between closely related genomes. Nucleic Acids Res. 30 (14), e71 [+]

    New whole-genome approach to comparison of LTR distribution in genomes of related species was presented. The eleven LTR insertions distinguishing human genome from chimpanzee ones were described at the first time.

  10. Buzdin A., Khodosevich K., Mamedov I., Vinogradova T., Lebedev Y., Hunsmann G., Sverdlov E. (2002). A technique for genome-wide identification of differences in the interspersed repeats integrations between closely related genomes and its application to detection of human-specific integrations of HERV-K LTRs. Genomics 79 (3), 413–22 [+]

    We have developed a method of targeted genomic difference analysis (TGDA) for genomewide detection of interspersed repeat integration site differences between closely related genomes. The method includes a whole-genome amplification of the flanks adjacent to target interspersed repetitive elements in both genomic DNAs under comparison, and subtractive hybridization (SH) of the selected amplicons. The potential of TGDA was demonstrated by the detection of differences in the integration sites of human endogenous retroviruses K (HERV-K) and related solitary long terminal repeats (LTRs) between the human and chimpanzee genomes. Of 55 randomly sequenced clones from a library enriched with human-specific integration (HSI) sites, 33 (60%) represented HSIs. All the human-specific (Hs) LTRs belong to two related evolutionarily young groups, suggesting simultaneous activity of two master genes in the hominid lineage. No deletion/insertion polymorphism was detected for the LTR HSIs for 25 unrelated caucasoid individuals. We also discuss the possible research applications for TGDA research.

  11. Lebedev Y.B., Belonovitch O.S., Zybrova N.V., Khil P.P., Kurdyukov S.G., Vinogradova T.V., Hunsmann G., Sverdlov E.D. (2000). Differences in HERV-K LTR insertions in orthologous loci of humans and great apes. Gene 247 (1-2), 265–77 [+]

    The classification of the long terminal repeats (LTRs) of the human endogenous retrovirus HERV-K (HML-2) family was refined according to diagnostic differences between the LTR sequences. The mutation rate was estimated to be approximately equal for LTRs belonging to different families and branches of human endogenous retroviruses (HERVs). An average mutation rate value was calculated based on differences between LTRs of the same HERV and was found to be 0.13% per million years (Myr). Using this value, the ages of different LTR groups belonging to the LTR HML-2 subfamily were found to vary from 3 to 50Myr. Orthologous potential LTR-containing loci from different primate species were PCR amplified using primers corresponding to the genomic sequences flanking LTR integration sites. This allowed us to calculate the phylogenetic times of LTR integrations in primate lineages in the course of the evolution and to demonstrate that they are in good agreement with the LTR ages calculated from the mutation rates. Human-specific integrations for some very young LTRs were demonstrated. The possibility of LTRs and HERVs involvement in the evolution of primates is discussed.