Kotelevtsev Laboratory

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Start date – December 2013

The research in our laboratory  is focused on the discovery and validation of new drug targets and on the development of new therapeuric platforms using animal models of human desieases.

Liver fibrosis
We have shown antifibrotic action of 4 methylumbelliferone (4MU), a hyaluronan synthase (HAS) inhibitor, in mouse model of liver fibrosis  (paper in preparation).  We are  investigating the cellular and molecular mechanisms of  hepatocyte injury and repair reactions leading to scar formation. This process involves macrophage activation, hepatic stellate cells differentiation to myofibroblasts, activation of matrix remodelling enzymes. 4 MU has a complex effect on these processes. Its integrative action causes diminished collagen and hyaluronan deposition. Our main goals are:
– To establish screening platform for HAS inhibitors and to identify new compounds reducing deposition of hyaluronan.
– To characterize anti fibrotic action of HAS inhibitors.
– To conduct pilot clinical trial on patients with early stages of liver fibrosis treated with hymecromone (4 methylumbelliferone) (Together with Sechenov Medical University).
– To establish a panel of LNP RNAi preparations , targeting 12-15 genes, for in vivo studies of liver fibrosis, hepatocellular carcinoma and liver regeneration.

Heart failure
- To investigate effect of itaconate derivatives on modulation of post MI immune response.
– To investigate the role of hyaluronan mediated processes in post MI scar formation.

Duchenne muscular dystrophy
- Efficacy characterization of therapeutic AAV expressing mini utrohin gene under synthetic promoter in transgenic mouse model mdx mice (in collaboration with Marlin Biotech).
–  Development of protocol for high scale production of utrophin expressing AAV suitable for phase I clinical studies.

Stress related disorders with glucocorticoid overreaction
- Development of in vivo corticosteroid sensor based on Surface Enhanced Raman Spectroscopy (SERS) in collaboration with PQM CREI.

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Supervisor – Yuri Kotelevtsev

Team: Irina Andreichenko Mikhail Nesterchuk
 Phd Students: Pavel Kusov
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College of Medicine and Veterinary Medicine, University of Edinburgh,  Edinburgh, Professor Stuart Forbes, Director  Scottish Centre for Regenerative Medicine.

 
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IM Sechenov First Moscow State Medical University, Moscow, Professor Chevdar Pavlov, President of Russian Scientific Liver Society, Department of hepathology.

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Marlin Biotech, Moscow, Tatiana Dimitrieva, Scientific Director.


MSc 2018
MSc 2017
Transgenic Models for Drug Discovery