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Invited researcher John J. Lemasters
Contract number
14.Z50.31.0028
Time span of the project
2014-2018
Head of the laboratory

As of 15.02.2021

18
Number of staff members
75
scientific publications
7
Objects of intellectual property
General information
Name of the project: Development of medication with targeted influence on mitochondrial pores and channels for treatment of heart and liver diseases and cancer therapy

Strategy for Scientific and Technological Development Priority Level: в

Goals and objectives
Research directions: Role of porin channels, other pores and channels of mitochondria in formation of multi-cell resistance of tumor cells against targeted drugs, in development of alcoholic-induced liver injury and cardiomyopathy, ischemic stress other types of pathophysiological conditions. Development of approaches for selective modulation of permeability of mitochondria for correction of various type of pathological conditions

Project objective: Determining main mitochondrial and cellular mechanisms targets for development of approaches of selective influence on mitochondrial pores for creation of drugs with targeted action for treatment of heart and liver diseases and cancer therapy

The practical value of the study

A new species was shown and the main mechanisms of multicellular resistivity of leukemic cells were investigated. The mechanism of increasing the resistance of cells of acute myeloid leukemia to death induced by DNA-tropic compounds, based on the activation of adhesion to the main molecules of the extracellular matrix, has been investigated. A new mitochondria-oriented mechanism of the antitumor action of melatonin has been shown. A new mechanism of astaxanthin cardioprotective action has been shown. A new mechanism of mTPP regulation has been investigated due to the participation of cytosolic NADH and NAD, which are potent inhibitors of mTPP in differentiated cells. It has been shown that a high-salt diet leads to the development of hypertensive nephrosclerosis, due to a decrease in oxygen consumption, suppression of the renal antioxidant system and an increase in oxidative stress in the renal cortical glomeruli.

Implemented results of research:

The method for personalized screening of drug action on leukemic cells ex vivo.

It is used on the basis of the Department of Hematology and Immunotherapy of the Moscow Regional Research Clinical Institute named after V.I. MF Vladimirsky ”, to predict the success of personalized therapy for acute leukemia.

Education and career development:

Educational courses:

  1. "Experimental Biomedicine" (Lomonosov Moscow State University, Faculty of Biotechnology, bachelor's degree).
  2. "Biotechnology of animal and human cells" (Lomonosov Moscow State University, Faculty of Biotechnology, Master's degree).
  3. "Pharmaceutical screening of drugs and promising substances in vitro" (PushGENI, Faculty of Biophysics and Biomedicine, Master's degree).

Teaching aids:

  1. Akatov V.S., Fadeev R.S., Fadeeva I.S., Shatalin Yu.V., Fesenko N.I. Pharmaceutical screening of drugs and promising substances in vitro. 2014. - Publ .: "FixPrint", Pushchino, 62 pages, ISBN 978-5-903789-21-4.
  2. Fadeeva I.S., Fadeev R.S., Senotov A.S., Akatov V.S. In vivo bioscreening of materials, preparations and promising substances. 2016. - Ed. SynchroBook, Pushchino, 59 pages, ISBN 978-5-91874-042-2.

Work shops:

  1. "ADVANCED DRUG DESIGN TECHNOLOGIES: MULTI-PARAMETER HCS SCREENING FOR INNOVATIVE DRUGS SEARCH" (2014).
  2. "THE BASIS OF 2D-ELECTROPHORESIS" (2015-2016).
  3. "BIOIMAGING MICROSCOPY" (2015).
  4. “SEMINAR ON PURIFICATION AND SEPARATION OF PROTEINS. TGX STAIN FREE TECHNOLOGIES "(2016).
  5. " xMAP AND GENE EXPRESSION ANALYSIS" (2016).
  6. "ORGANIZATION OF BEHAVIORAL EXPERIMENTS ON LABORATORY ANIMALS: VALIDATION, WORLD STANDARDS" (2016).
  7. "DETERMINATION OF CELL VIABILITY BY METHODS OF FLOW CYTOMETRY" (2017).
  8. "MODERN TECHNOLOGIES OF CELLULAR IMAGING" (2017).
  9. " PCR SCHOOL " (2017).

Training of highly qualified personnel:

Nikiforova Anna Borisovna, PhD in Biology, 2015

Kharechkina Ekaterina Sergeevna, PhD in Biology, 2021

Collaborations:

Moscow Regional Clinical Research Institute named after M.F. Vladimirsky (Russia), Lomonosov Moscow State University (Russia), Institute of Immunology FMBA of Russia, Institute of Gene Biology Russian Academy of Sciences, Institute of Molecular Biology named after V.A. Engelhardt Russian Academy of Sciences, Belozersky Research Institute of Physical and Chemical Biology, Moscow State University (Russia), Medical University of South Carolina, Charleston, SC (USA), Aurora Health Care, Milwaukee (Wisconsin, USA): scientific cooperation.

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Krestinin R., Baburina Y., Odinokova I., Kruglov A., Fadeeva I., Zvyagina A., Sotnikova L., Krestinina O.
Isoproterenol-induced permeability transition pore-related dysfunction of heart mitochondria is attenuated by astaxanthin, BIOMEDICINES. 2020, 8, 10, 437
Lomovsky A., Baburina Y., Odinokova I., Kobyakova M., Evstratova Y., Sotnikova L., Krestinin R., Krestinina O.
Melatonin can modulate the effect of navitoclax (Abt-737) in hl-60 cells, ANTIOXIDANTS. 2020, 9, 11, 1143
Solovieva M., Shatalin Y., Fadeev R., Krestinina O., Baburina Y., Kruglov A., Kharechkina E., Kobyakova M., Rogachevsky V., Shishkova E., Akatov V.
Vitamin B12b enhances the cytotoxicity of diethyldithiocarbamate in a synergistic manner, inducing the paraptosis-like death of human larynx carcinoma cells. BIOMOLECULES. 2020, 10, 1, 69
Fadeev, R; Chekanov, A; Solovieva, M; Bezborodova, O; Nemtsova, E; Dolgikh, N; Fadeeva, I; Senotov, A; Kobyakova, M; Evstratova, Y; Yakubovskaya, R; Akatov, V.
Improved anticancer effect of recombinant protein izTRAIL combined with sorafenib and peptide IRGD. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2019, 20, 3, 525
Zotova, A; Pichugin, A; Atemasova, A; Knyazhanskaya, E; Lopatukhina, E; Mitkin, N; Holmuhamedov, E; Gottikh, M; Kuprashs, D; Filatov, A; Mazurov, D.
Isolation of gene-edited cells via knock-in of short glycophosphatidylinositol-anchored epitope tags. Scientific reports, 2019, 9, 3132
Harechkina E.S., Nikiforova A.B., Kruglov A.G.
Pyridine nucleotides regulate the superoxide anion flash upon permeabilization of mitochondrial membranes: An MCLA-based study. Free Radic Biol Med. 2018; 124: 473-483
Mukherjee R., Mareninova O.A., Odinokova I.V., Huang W., Murphy J., Chvanov M., Javed M.A., Wen L., Booth D.M., Cane M.C., Awais M., Gavillet B., Pruss R.M., Schaller S., Molkentin J.D., Tepikin A.V., Petersen O.H., Pandol S.J., Gukovsky I., Criddle D.N., Gukovskaya A.S., Sutton R.
Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP. Gut, 2016, 65, 1333-1346
Azarashvili T., Odinokova I., Krestinina O., Tyynelä J., Saris N.E.L., Bakunts A., Ternovsky V.
Potential role of subunit c of f0f1-atpase and subunit c of storage body in the mitochondrial permeability transition. effect of the phosphorylation status of subunit c on pore opening. Cell Calcium. 2014. 55, 2, 69-77
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