Activities studies of molecular genetic foundations for the formation of socially significant pathologies, new proteogenomic technologies of personalized medicine, which are in demand in clinical practice, are being developed for prevention, diagnostics and treatment of socially significant diseases, based on the individual diversity of systems, controlling the drug response and sensitivity to the damaging effects of xenobiotics.

Lyakhovich Vyacheslav Valentinovych

Head of the Laboratory - Academician of the Russian Academy of Sciences, Doctor of Biological Sciences, professor

lyakh@niimbb.ru

vvlyakhovich@frcftm.ru

V.V. Lyakhovich was born 21 October 1939 years in. Novosibirsk. AT 1963 G. graduated from the medical faculty of the Novosibirsk Medical Institute, then clinical residency at the Department of Radiology and Radiology. S 1965 on 1973 G. - Researcher at the Central Scientific Research Laboratory at the Novosibirsk State Medical Institute. AT 1973 – 1992 gg – Head of the Laboratory of Cellular Adaptation Mechanisms, Department of Cell Physiology and Pathology, Deputy Director for Research at the Research Institute of Clinical and Experimental Medicine of the Siberian Branch of the USSR Academy of Medical Sciences. AT 1992 G. headed the Research Institute of Molecular Pathology and Ecological Biochemistry, in 1998 G. – Research Institute of Molecular Biology and Biophysics SB RAMS, which he led during 17 years.

Scientific activity of V.V.. Lyakhovich began immediately after graduating from NSMI at the Department of Radiology and Radiology and at the Central Scientific Research Institute, and in 1966 G. he defended his Ph.D. thesis “Violation of tissue respiration of breast tumors during fractional irradiation”, and in 1974 G. – doctoral thesis "Membrane organization and biochemical functions of mitochondria and microsomes". Both works were carried out in close cooperation with the leader of Soviet science in this field of knowledge - Vladimir Petrovich Skulachev. AT 1981 G. V.V. Lyakhovich was approved as a professor, in 1988 was elected a corresponding member of the USSR Academy of Medical Sciences with a degree in molecular biology, and in 1994 year - a full member of the Russian Academy of Medical Sciences in the specialty "biochemistry". S 2013 d – Academician of the Russian Academy of Sciences in the Department of Medical Sciences of the Russian Academy of Sciences.

Following the work on bioenergetics, the stage of studying free-radical processes of lipid peroxidation followed. (POL) in biomembranes - the phenomenon, involved in the development of many pathological conditions. On model systems and natural membranes, the characteristics of enzymatic lipid peroxidation and factors, controlling this process. Installed, that in endoplasmic membranes the main center of radical formation is NADPH-specific flavoprotein.

Since the beginning of the 80s, the main direction of scientific activity of V.V.. Lyakhovich – fundamental and applied research of the enzymatic system of biotransformation of xenobiotics. The development of methods of preparative biochemistry in the team led by him ensured the production of a number of individual cytochromes P-450 in pure form., creation of a bank of monoclonal antibodies, allowing quantitative determination of molecular forms of cytochrome P-450 in biological samples. Studies of the mechanisms of monooxygenase reactions have been carried out, studied the properties of electron carriers – NADPH-cytochrome P450 reductase and multiple forms of cytochrome P450 in microsomes, purified protein preparations, reconstructed membrane systems; new knowledge about the localization of active centers was obtained, stoichiometry and interaction of protein components of monooxygenases in membranes, molecular modeling of the active centers of cytochromes P4501A1 and 2B1 was carried out. A new class of inhibitors of monooxygenase reactions has been developed, covalently binding to the SH group of the active center of cytochrome P450. Data have been obtained on the possibility of in vivo transport of these inhibitors into liver cells in liposomes..

In the 90s, the attention of V.V.. Lyakhovich and colleagues were concentrated on the problems of chemical ecology. An important area of ​​work was the study of the induction of xenobiotic biotransformation enzymes. (FBK). Research in this area has revealed- and tissue-specific regulatory factors. During this period, on the basis of fundamental research, a method was developed for a comprehensive assessment of xenobiotic metabolism systems in humans., including determination of the genotypes of individual P450s and non-invasive pharmacokinetic analysis of their activities using test drugs - selective substrates of these P450s. This was followed by a transition to studies of associations of polymorphic variants of FBK genes with a predisposition to multifactorial diseases., which are still ongoing.

In close cooperation with healthcare institutions, research is being developed on the molecular genetic basis for the formation of socially significant pathologies., in directions such as: gene polymorphism and predisposition to the development of multifactorial pathologies, influence of genetic factors on drug response, first of all, the role of polymorphism of genes of transport proteins and enzymes of drug metabolism in the formation of multidrug resistance of tumor cells in oncohematological patients. Search for new molecular genetic markers of tumor tissue transformation is underway. New molecular biological technologies in demand in clinical practice are being developed for predicting, more accurate diagnosis and effective personalized drug therapy of oncological diseases.

V.V. Lyakhovich published over 500 scientific papers, prepared 7 doctors and 22 candidate of science. Scientific activity of Academician V.V.. Lyakhovich is closely associated with the scientific and organizational. For a number of years he was a member of the Coordinating and Expert Council on the Problems of Nanotechnologies and Nanomaterials at the Presidium of the Russian Academy of Medical Sciences.. V.V. Lyakhovich is a member of the editorial board of the journal “Biomedical Chemistry”, Editorial Board of the Siberian Scientific Medical Journal. Takes part in the work of dissertation councils at the Research Institute of Biochemistry FRC FTM and FBSI State Scientific Center of Virology and Biotechnology "Vector" of Rospotrebnadzor. The level of scientific research V.V.. Lyakhovich was awarded the title of laureate of the Prize of the Russian Academy of Medical Sciences named after N.I.. Pirogov 1994 years for the cycle of work “Systemic mechanisms of adaptive-compensatory reactions under the influence of environmental factors on the body”, Laureate of the State Prize of the Russian Federation for Science and Technology 1998 years for work “Microsomal oxidation and drug metabolism: mechanisms of oxidative reactions, catalyzed by cytochromes P450, and their modeling” and the Paul Ehrlich Medal of Honor (2004 G). For many years of fruitful scientific activity V.V.. Lyakhovich was awarded the medal "For Labor Distinction"

Research results of the division:

Shown, that in the presence or absence of lymphogenous metastasis, the index of the influence of polyclonal activators on the production of cytokines by immunocompetent blood cells differed in three indicators: IL-6, IL-8 and IL-1β. The presence of lymphogenous metastases corresponded to an increase in spontaneous production of cytokines., and their absence - an increase in production, stimulated by polyclonal activators. Polyclonal activators cause an increase in the relative content of highly differentiated cells of non-specific invasive breast carcinoma. Based on the results obtained, a risk group for metastasis among women was proposed., not having metastases in the lymph nodes at the time of the study. Shown, that in patients with fibroadenoma, compared with patients with invasive carcinoma of a non-specific type, there is a higher concentration of PR in the blood serum. The index of influence of polyclonal activators on PR production by breast tissue samples is inversely correlated with CII expression in breast tissue samples.. Installed, that patients with fibroadenomatosis have a lower concentration of IL-12 and a higher concentration of CDH1 in blood cell supernatants compared with patients with non-specific invasive carcinoma. Shown, what is the differentiation factor HLDF (Human Leukemia Differentiation Factor) causes a decrease in the relative content of poorly differentiated cells and an increase in the relative content of highly differentiated cells of invasive breast carcinoma of a nonspecific type. The concentration of IL-12 and ERα in blood serum is in direct correlation, and the concentration of CDH1 in the supernatant of blood cells – inversely correlated with CDH1 expression in breast tissue samples. Discovered, that the index of influence of HLDF on CDH1 production is higher in those samples, in which HRG mRNA was present, and the index of influence of HLDF on HRG products is lower in those samples, in which HRG mRNA is expressed. The index of the effect of HLDF on the production of ERα by samples of breast tissue in non-specific invasive carcinoma is lower, than in benign breast disease. Shown, that the differentiation factor HLDF affects protein production to a greater extent in non-specific invasive carcinoma and in fibroadenomatosis, which allows us to consider it as a candidate for differentiating therapy.

Solving these problems will allow developing strategies for optimizing postoperative treatment of glioblastoma., which will reduce its negative side effects, improving the effectiveness of treatment and quality of life of patients with this disease. The work of the laboratory is consistently supported by RFBR grants, Russian Science Foundation and administration of the Novosibirsk region.

Publications

  1. Autenslyus A.I., Brusentsov I.I., Marinkin I.O., Smirnova S.A., Rukavishnikov M.Yu., Lyakhovich V.V. mRNA of histidine-rich glycoprotein in breast neoplasms // Reports of the Academy of Sciences.- 2018.- T. 478, № 5.- S. 596-600.
  2. A. AND. Autenschluss, AND. D. Ivanov, A. AT. Golovanova, A. A. Studenikina, Well. S. Mihailova, AT. A. Bavilin, N. A. Varaxin, AT. AT. Lyakhovich. Comparison of cytokine mRNA expression with their concentration in the supernatant of u937 cell culture exposed to polyclonal activators // Medical immunology.- 2019, T. 21, №4, P.737-742.
  3. A. AND. Autenschluss, A. AT. Golovanova, A. A. Studenikina, AND. AND. Brusentsov, A. AT. The transparency, AND. P. Zhurakovsky, S. A. Arkhipov, S. AT. Sidorov, AT. A. Bavilin, AT. AT. Lyakhovich. A personalized approach to assessing the expression of histidine-rich glycoprotein mRNA and immunohistochemical markers in breast diseases. // Reports of the Academy of Sciences. 2019. T. 484, № 5. S. 624-628
  4. Autenslyus A.I., Studenikina A.A., Bernado A.V., Mihailova E.S., Proskura A.V., Sidorov S.V., Varaksin N.A., Lyakhovich V.V. Evaluation of the cytokine-producing resource of tumor biopsy specimens from patients with non-specific invasive carcinoma and non-malignant breast diseases // Biomedical Chemistry. 2019. Volume 65, No. 5, S. 418-423.
  5. Autenslyus A.I., Davletova K.I., Studenikina A.A., Mihailova E.S., Varaksin N.A., Zhurakovsky I.P., Proskura A.V., Sidorov S.V., Lyakhovich V.V. Production of cytokines by immunocompetent blood cells, tumor and its microenvironment, features of the state of the extracellular matrix in patients with invasive breast carcinoma of a nonspecific type // Biomedical Chemistry. 2019. Volume 65, № 5, S. 424-431.
  6. Autenslyus AI, Bernard AV, Studenikina AA, Proskura OFF, Davletova KI, Zhurakovskiy IP, Arkhipov SA, Varaksin NA, Sidorov SV, Lyakhovich VV. Personalized Approach to Determination of Histidine-Rich Glycoprotein and E-Cadherin in Supernatants of Immunocompetent Blood Cells and Breast Biopsy Specimens in Breast Malignant and Non-Malignant Disease. Dokl Biochem Biophys. 2020 Jan;490(1):1-4. doi: 10.1134/S1607672920010019. Epub 2020 Apr 27. PMID: 32342301. (WoS)
  7. Autenshlyus A.I., Davletova K.I., Mikhaylova E.S., Proskura A.V., Varaksi N.A., Bogachuk A.P., Sidorov S.V., Lyakhovich V.V., Lipkin V.M. Influence of Internal and External Factors on the Production of Cytokines by Peripheral Blood Cells in Breast Cancer // Doklady Biochemistry and Biophysics. – 2020. – V. 493. – № 1. – P. 178-180. DOI: 10.1134/S1607672920040031 (WoS)
  8. Autenschlyus AI, Bernard AV, Davletova KI, Arkhipov SA, Zhurakovsky IP, Mikhailova ES, Proskura OFF, Bogachuk A.P., Lipkin VM, Lyakhovich VV. Belkovye i immunogistokhimicheskie markery zabolevaniĭ molochnoĭ zhelezy [Proteins and immunohistochemical markers of breast diseases]. Biomed Chem. 2020 Feb;66(2):167-173. Russian. doi: 10.18097/PBMC20206602167. PMID: 32420899. (SCOPUS)
  9. A.I. Autenslyus, A.A. Studenikina, S.A. Arkhipov, K.I. Davletova, I.P. Zhurakovsky, A.V. Proskura, N.A. I would save, V.V. Lyakhovich. Relationship Between Superatant Cytokines And Expression Of Markers Of Epitelial-Mesenchymal Transition Of Invasive Breast Carcinoma Of Non-Specific Lymphynosis Type. Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 2020, Vol. 14, No. 3, pp. 260–265. DOI: 10.1134/S1990750820030038. (SCOPUS)
  10. Autenshlyus A.I., Davletova K.I., Studenikina A.A., E. S. Mikhaylova E.S., Varaksi N.A., Zhurakovsky I.P., Proskura A.V., Sidorov S.A., Lyakhovich V.V.. Cytokine Production by Blood Immune Cells, Tumor and Its Microenvironment, Characteristics of Extracellular Matrix in Patients with Invasive Ductal Carcinoma of No Special Type. DOI: 10.18097/PBMC20196505424 // Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry. – 2020. – V. 14. – № 1. – P. 44-51. (SCOPUS)
  11. A. Autenslyus, S. Arkhipov, E. Mikhailova, I. Marin too, N. I would save, V. Vavilin and V. Lyakhovich Еffects of polyclonal activators on cell differentiation and cytokine production of cultured invasive breast carcinoma of no special type, their association with tumour histopathological parameters and lymph node metastasis //International Journal of Immunopathology and Pharmacology Volume 34: 1–11 DOI:10.1177/2058738420950580 (WoS, Q2)
  12. A. I. Autenshlyusa, A. A. Studenikina, A. V. Bernado, E. S. Mikhailova, A. V. Proskura, S. V. Sidorov, N. A. I would save, V. V. Lyakhovich. Assessment of the Cytokine-Producing Resource of Tumor Biopsy Samples from Patients with Invasive Carcinoma of No Special Type and with Non-Malignant Breast Diseases. Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 2020, Vol. 14, No. 1, pp. 38–43. DOI: 10.18097/pbmc20196505418. (SCOPUS)
  13. Autenslyus A.I., Studenikina A.A., Mihailova E.S., Proskura A.V., Varaksin N.A., Sidorov S.V., Bogachuk A.P., Lipkin V.M., Lyakhovich V.V. Influence of the differentiation factor HLDF on the production of cytokines by biopsy specimens of breast tissue in non-malignant breast tissue diseases and in non-specific invasive carcinoma // Biomedical Chemistry, 2020 volume 66, issue. 6, With. 485-493.
  14. Alexander Autenshlyus, Sergey Arkhipov, Elena Mikhaylo-va1,2, Igor Marinkin,Valentina Arkhipova, Nikolay Varaksin, Valentin Vavilin & Vyacheslav Lyahovich Analyzing the relationship between the cytokine profile of invasive breast carcinoma, its histopathological characteristics and metastasis to regional lymph nodes// Sientific reports (2021) 11:11359 DOI: 10.1038/s41598-021-90930-z (WoS), Q1
  15. Alexsander Autenshlyus, Kristina Davletova, Nikolay Varaksin Igor Marinkin and Vyacheslav Lyakhovich Cytokines in various molecular subtypes of breast cancer//International Journal of Immunopathology and Pharmacology Volume 35: 1–13 DOI: 10.1177/20587384211034089 (WoS), Q2
  16. A. I. Autenshlyus A. A. Studenikina, N. A. I would save, and Academician V. V. Lyakhovich Cytokine Production by Tumor Bioptate at Different Pathological Prognostic Stages in Breast Cancer// Doklady Biochemistry and Biophysics, 2021, Vol. 497, pp. 86–89 published in Doklady Rossiiskoi Akademii Nauk. Science about Zhizni, 2021, Vol. 497, pp. 180–184. DOI: 10.1134/S1607672921020010 (WoS), Q4
  17. Autenslyus A.I., Zhurakovsky I.P., Arkhipov S.A., Arkhipova V.V., Lyakhovich V.V. Comparative evaluation of the expression of markers of proliferation and epithelial-mesenchymal transition in malignant and non-malignant diseases of the breast//Modern problems of science and education. – 2022. – № 6 (Part 1). URL: https://science-education.ru/ru/article/view?id=32241

Patents

  • RF Patent No. 2646787 "Method for determining the metastatic potential of a breast tumor". Date of registration: 07.03.2018. The author: Zhurakovsky Igor Pavlovich, Arkhipov Sergey Alekseevich, Marinkin Igor Olegovich, Autenschluss Alexander Isaevich. Published: 07.03.2018, Bull. № 7.
  • RF Patent No. 2697055 "Method for determining the metastatic potential of invasive ductal breast cancer and composition for its implementation". Date of registration: 09.08.2019. The author: Autenschluss Alexander Isaevich, Zhurakovsky Igor Pavlovich, Davletova Kristina Igorevna, Marinkin Igor Olegovich. Published: 09.08.2019 Bull. № 22
  • RF Patent No. 2697199 "Composition for increasing the content of highly differentiated cells in breast adenocarcinoma". Date of registration: 13.08.2019. The author: Autenschluss Alexander Isaevich, Arkhipov Sergey Alekseevich, Mikhailova Elena Semyonovna, Varaksin Nikolai Anatolievich, Marinkin Igor Olegovich. Published: 13.08.2019 Bull. № 23
  • RF Patent No. 2705398 "Method for predicting the effectiveness of the use of an agent for increasing the relative content of highly differentiated cells in breast adenocarcinoma and a composition for its implementation". Date of registration: 07.11.2019. The author: Autenschluss Alexander Isaevich, Arkhipov Sergey Alekseevich, Mikhailova Elena Semyonovna, Varaksin Nikolai Anatolievich, Marinkin Igor Olegovich Published: 07.11.2019 Bull. № 3
  • RF Patent No. 2 743710 «A means, reducing the relative content of low-differentiated and increasing the relative content of highly differentiated cells in invasive non-specific breast carcinoma". Date of registration: 24.02.2021. The author: Autenschluss Alexander Isaevich, Zhurakovsky Igor Pavlovich, Mikhailova Elena Semyonovna, Davletova Kristina Igorevna, Bernado Albina Vladimirovna, Studenkina Anastasia Alexandrovna, Andrey Viktorovich Proskura, Sidorov Sergey Vasilievich, Marinkin Igor Olegovich, Lyakhovich Vyacheslav Valentinovych, Bogachuk Anna Payzenovna, Lipkin Valery Mikhailovich.

Laboratory staff

  1. Safronova Olga Gennadievna, Leading Researcher, candidate of biological sciences
    ogsafronova@frcftm.ru
    saf@niimbb.ru
    rt +7 (383) 274 9552
  2. Kononchuk Vladislav Vladimirovich, junior researcher
    vvkononchuk@frcftm.ru