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Research Laboratory «Molecular Immunology»

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As of 01.11.2022

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scientific publications
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General information
Name of the project: mTOR1 regulation in the process of mitochondrial metabolism: the impact on inflammation and carcinogenesis

Goals and objectives

The goal of this project is the study of the impact of metabolic reprogramming of mitochondria on the function of macrophage in the immune response to cancer cells in carcinogenesis, as well as to parasitic infection in translational medicine. In relation to this, the following tasks have been set:

  1. To research the role of mitochondria in metabolic reprogramming of macrophage in vivo;
  2. To study the impact of mitochondrial adaptations on the functional properties and the polarisation of macrophage both in vitro and in vivo;
  3. To forecast the composition of a hypothetical signalling pathway binding mitochondria and mTORC1 activity;
  4. To determine a possible role of mitochondrial adaptations in metabolic and functional rearrangements in cancer cells using corresponding animal models.

The supposed new connection between mitochondria and mTORC1 activity is a general regulatory mechanism that is necessary for the functional adaptation of cells. In this project, the focus is laid on immune reactions and oncogenesis.

The practical value of the study

Scientific results:

For the first time it has been found that microphages with OPA1 knockout, i. e. with mitochondrial dysfunction, demonstrate a significant increase in the level of p70S6K and p85S6K kinase phosphorylation and, therefore, mTORC1 activation. Moreover, it was found that mitochondrial dysfunction leads to an increase in mTORC1 activation in cells to a higher level in comparison with native cells.

We have assessed the impact of the found mechanism — mTORC1 over-activation in macrophages with mitochondrial dysfunction on polymerase activity. We found a significant increase in ribosomal biogenesis and rRNA/tRNA maturation in microphages with mitochondrial dysfunction, which confirms the increased activity of mTORC1 activation in these cells.

It has been found that mTORC1 activation leads to autophagy inhibition.

It has been discovered that activated immune cells rapidly change their biosynthetic and metabolic characteristics in immune response.

In accordance with these rearrangements mitochondria of immune cells also demonstrate flexibility and correct their bioenergy as well as metabolic properties. It has been found that the same processes occur during oncogenesis.

It has been found that the regulation of mTORC1, the key sensor and modulator of metabolism is disturbed as a result of immune cells activation.

It is supposed that there exists a connection of the mTORC1 — mitochondria complex, which is responsible for the activation of pathways that support the proliferation of tumor and immune cells.

Implementation of research results:

We have developed a technology for assessing mitochondrial metabolism in naive, pro-inflammatory and alternatively activated macrophages. We have established a connection between metabolic changes in cells and the activation of the mTORC1 molecular pathway.

The Laboratory has created a model of a hypothetical relation between metabolic rearrangements caused by mitochondrial dysfunction in human cells, and mTORC1 over-activation. It has been found that immune cells with defective mitochondria, with decreased respiration, are able to support a high level of mTORC1 activity and biosynthesis processes.

The area of use of said designs is the basic and applied research of carcinogenesis, mitochondrial metabolism, immunology as well as the development and implementation of new antitumor therapeutic strategies (by pharmaceutical companies, research and clinical centers).

Education and retraining of personnel:

  • In 2021-2022 we conducted 5 internships of postgraduates at the leading scientist’s laboratory.
  • In 2021 three members of our team completed an additional training course in biotechnology.
  • In 2022 on the basis of the Laboratory the international conference «Symposium on the advances in cancer research in 2022» was staged that attracted 100 registered participants.


University of Bern (Switzerland), University of Marburg (Germany), Moscow Institute of Physics and Technology (national research university), Kazan (Volga region) Federal University (Russia): joint research.

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hans-uwe simon
The eosinophil and its role in physiology and disease: news and views. Seminars in Immunopathology - 2021, июнь (Т. 43, №. 3), Q1.
timothée fettrelet, lea gigon, alexander karaulov, shida yousefi, hans-uwe simon
The Enigma of Eosinophil Degranulation - International Journal of Molecular Sciences – 2021, июнь (Т. 22, №. 13), Q1.
živa frangež, deborah gérard, zhaoyue he, marios gavriil, yuniel fernández-marrero, s. morteza seyed jafari, robert e. hunger, philippe lucarelli, shida yousefi, thomas sauter, lasse sinkkonen and hans-uwe simon
ATG5 and ATG7 Expression Levels Are Reduced in Cutaneous Melanoma and Regulated by NRF1. Frontiers in Oncology - 2021, август (№. 11), Q2.
andreina bruno, caterina di sano, hans-uwe simon, pascal chanez, angelo maria patti, serena di vincenzo, paola dino, vittoria d’esposito, pietro formisano, francesco beguinot and elisabetta pace
Leptin and TGF-beta 1 Downregulate PREP1 Expression in Human Adipose-Derived Mesenchymal Stem Cells and Mature Adipocytes. Frontiers in Cell and Developmental Biology - 2021, июль, (Т.13, №9, С.700481. doi: 10.3389/fcell.2021.700481. eCollection 2021.), Q1.
leonardo cristinziano, luca modestino, alessandro antonelli, gianni marone, hans-uwe simon, gilda varricchi, maria rosaria galdiero
Neutrophil extracellular traps in cancer. Seminars in Cancer Biology - 2021, июль, (doi: 10.1016/j.semcancer.2021.07.011. ), Q1.
kim klapan, živa frangež, nikita markov, shida yousefi, dagmar simon, hans-uwe simon
Evidence for Lysosomal Dysfunction within the Epidermis in Psoriasis and Atopic Dermatitis. J. Invest. Dermatol - 2021, декабрь, (Т.141, выпуск 12), Q1.
valeriia syromiatnikova, angelina prokopeva and marina gomzikova
Methods of the Large-Scale Production of Extracellular Vesicles. International journal of Molecular Sciences- 2022, 23, 10522. Сентябрь https://doi.org/10.3390/ ijms231810522, Q1.
kim klapan, dagmar simon, alexander karaulov, marina gomzikova, albert rizvanov, shida yousefi and hans-uwe simon
Autophagy and Skin Diseases. Frontiers in Pharmacology – 2022, Январь, 13:844756. doi: 10.3389/fphar.2022.844756. Q1.
darko stojkov, lea gigon, shuang peng, robert lukowski, peter ruth, alexander karaulov, albert rizvanov, nickolai a. barlev, shida yousefi and hans-uwe simon
Physiological and Pathophysiological Roles of Metabolic Pathways for NET Formation and Other Neutrophil Functions. Frontiers in Immunology – 2022, Февраль. 13:826515. doi: 10.3389/fimmu.2022.826515.Q1.
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