Group for Genomic Regulation of Cell Signaling Systems

Department of Genomics and Postgenomic Technologies

Head: Anton Buzdin, D.Sc
bu3din@mail.ru+7(495)727-38-63

www.ibch.ru/gensensor/ggassk.htm

Genome- and Transcriptome Wide Analysis of Gene Expression in Higher Eukaryotes; Identification of Major Molecular Genetic Aspects of Human Speciation; Engineering of human tissue specific gene regulatory sequences; Recovery of new molecular genetic oncom

Our group exists since February 2006 when it had separated from the group supervised by Dr. Yuri Lebedev in the Laboratory of Human Genes Structure and Functions. First of all, the head of the above laboratory, professor Eugene Sverdlov, is our scientific guru.

  1. Functional genomic analysis of human specific DNA
  2. Design of new experimental techniques for large scale functional studies of the complex genomes
  3. Engineering of gene regulatory sequences
  1. Discovery of chimeric retroelements in the mammalian genomes
  2. Development of new experimental techniques for functional genomics
  3. Identification of gene regulatory regions in the human specific DNA
  4. Directed differentiation of several stem cell cultures

All publications (show selected)

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Anton Buzdin

  • Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map
  • IBCh RAS, build. 51, office. 663
  • Phone: +7(495)727-38-63
  • E-mail: bu3din@mail.ru

Disparity between Inter-Patient Molecular Heterogeneity and Repertoires of Target Drugs Used for Different Types of Cancer in Clinical Oncology

For the first time, we compared repertoires of approved targeted cancer drugs with the real intragroup heterogeneity in different human tumor types. We analyzed 4980 tumor tissue samples representing 13 most abundant human solid cancers, for which whole-exome mutational profiles and whole-transcriptome profiles were available. We first explored whether the number of approved drugs (projected to the number of their molecular targets) is proportionate to the intragroup heterogeneity in each cancer type: using data for all genes, and for molecular drug target genes only. We found there is no connection between the observed molecular heterogeneity and wealth of the spectrum of the approved drugs, for both genomic and transcriptomic data. We then compared quantitative characteristics: how treatment regimens for different cancer types relate to their molecular profiles. For the first time we found that tumor type classification according to treatment regimens relates to their classification according to gene expression profiles. We found the best connection between the cancer treatment methods and molecular profiles for the kidney, gastric, bladder, ovarian and endometrial tumors; in turn, the worst match was documented for the brain tumors, prostate and colorectal cancers.

Publications

  1. Zolotovskaia MA, Sorokin MI, Petrov IV, Poddubskaya EV, Moiseev AA, Sekacheva MI, Borisov NM, Tkachev VS, Garazha AV, Kaprin AD, Shegay PV, Giese A, Kim E, Roumiantsev SA, Buzdin AA (2020). Disparity between Inter-Patient Molecular Heterogeneity and Repertoires of Target Drugs Used for Different Types of Cancer in Clinical Oncology. Int J Mol Sci 21 (5), 1–18

Coincidence of functional epigenetic marks and transposable elements enables measuring transcriptional regulation evolution rates of genes and molecular pathways

We developed bioinformatic method RetroSpect that enables measuring rates of evolution of transcriptional regulation of genes and molecular pathways based on coincidences of functional genomic epigenetic marks and transposable elements. We applied Retrospect to quantitative data on genomic distribution of transcription factor binding sites and histone marks: H3K4me1, H3K4me3, H3K9ac, H3K27ac, H3K27me3 and H3K9me3. The analysis of public databases demonstrated that the most strongly evolving processes (termed RRE-enriched) are connected with regulation of microRNAs, olfaction, fertilization, immune response, fatty acids metabolism and detoxication. In contrast, the most slowly evolving processes (RRE-deficient) dealt with protein translation, RNA transcription, maintaining chromatin structure and molecular signaling.

Publications

  1. Nikitin D, Kolosov N, Murzina A, Pats K, Zamyatin A, Tkachev V, Sorokin M, Kopylov P, Buzdin A (2019). Retroelement-Linked H3K4me1 Histone Tags Uncover Regulatory Evolution Trends of Gene Enhancers and Feature Quickly Evolving Molecular Processes in Human Physiology. Cells 8 (10),
  2. Igolkina AA, Zinkevich A, Karandasheva KO, Popov AA, Selifanova MV, Nikolaeva D, Tkachev V, Penzar D, Nikitin DM, Buzdin A (2019). H3K4me3, H3K9ac, H3K27ac, H3K27me3 and H3K9me3 Histone Tags Suggest Distinct Regulatory Evolution of Open and Condensed Chromatin Landmarks. Cells 8 (9),
  3. Nikitin D, Garazha A, Sorokin M, Penzar D, Tkachev V, Markov A, Gaifullin N, Borger P, Poltorak A, Buzdin A (2019). Correction: Nikitin, D., et al. Retroelement-Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution. 2019, , 130. Cells 8 (8),
  4. Nikitin D, Garazha A, Sorokin M, Penzar D, Tkachev V, Markov A, Gaifullin N, Borger P, Poltorak A, Buzdin A (2019). Retroelement-Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution. Cells 8 (2), 130

New methods of estimation of evolutional rate of molecular pathways

We showed that transcription factor binding sites in the vicinities of gene promoters, that colocalize with the transposable elements, may serve as the markers of the evolutional rate ofmolecular pathways. We found that in human ancestral lineage the most quickly evolving pathways were linked with immunity and response to pathogens, as well as for metabolism of fats and catabolism of heterocyclic molecules, and for formation of perception organs.