Research Centre of Unknown, Rare and Genetically Determined Diseases

Head of the Department — Elena Vasichkina.

Major tasks

To conduct basic research aimed at identifying new specific genetic determinants of congenital diseases and revealing the molecular mechanisms of their development, to create experimental cellular and animal models for testing new genetically engineered and gene therapy drugs for the treatment of hereditary disorders.

To use breakthrough genetic technologies, including eQTL mapping, assessment of expression and epigenetic profiling in order to reveal new phenotypic mechanisms of genetic breakdowns and the development of drugs targeting these mechanisms.

To create a scientific and clinical biomedical ecosystem that develops and implements diagnostic and treatment technologies based on personalized medicine, including disease biomodelling; genome modification and creation of gene therapy drugs and biomedical cell products using genome editing technologies to improve the quality of treatment and reduce mortality in various genetically determined cardiovascular, autoimmune as well as rare and understudied diseases.

Focus areas

The specialists of the Research Centre are implementing the following 10 projects:

Using multi-omics data to diagnose rare genetic diseases.
Creating models for genetically determined human diseases using induced pluripotent cells (iPCs).

Searching for new directions of targeted therapy for congenital and acquired diseases with excessive calcification.
Developing approaches to the creation and personalized use of gene therapy drugs for congenital genetic disorders of the neuromuscular and cardiovascular systems.
Creating a centre for disease biomodelling in rodents and Danio rerio using genome editing technologies.
Developing personalized technologies for the treatment of familial hypercholesterolemia based on pheno- and genotype profiles of patients.
Developing and testing of artificial intelligence-based detectors in wide population groups to detect children with rare and understudied congenital diseases for their early verification.
Creating a registry of unknown, rare and genetically determined diseases.
Creating a registry of congenital genetic cardiomyopathies in children.
Investigating the molecular mechanism of non-classical (non-monogenic) autoinflammatory diseases and searching for the directions for their targeted therapy.

Structure

Newly developed and implemented technologies

Next-generation targeted sequencing technologies

Microarray-based comparative genomic hybridization (array CGH)
Genome editing technologies
Functional studies using induced pluripotent stem cells
A new source and mechanism of specialization of certain stem cells, which can be used in the regeneration of human tissues.
A new nerve-dependent mechanism of cell-type specialization in early development.

Major publications

Spatiotemporal structure of cell fate decisions in murine neural crest. Soldatov R., Kaucka M., Kastriti M. E., Petersen J., Chontorotzea T., Englmaier L., Akkuratova N., Yang Y., Häring M., Dyachuk V., Bock C., Farlik M., Piacentino M. L., Boismoreau F., Hilscher M. M., Yokota C., Qian X., Nilsson M., Bronner M. E., Croci L., Hsiao W. Y., Guertin D. A., Brunet J. F., Consalez G. G., Ernfors P., Fried K., Kharchenko P. V., Adameyko I. Science. 2019. DOI: 10.1126/science.aas9536.
Schwann cell precursors contribute to skeletal formation during embryonic development in mice and zebrafish. Xie M., Kamenev D., Kaucka M., Kastriti M. E., Zhou B., Artemov A. V., Storer M., Fried K., Adameyko I., Dyachuk V., Chagin A.S.. Proceedings of the National Academy of Sciences, 2019. DOI: 10.1073/pnas.1900038116
Newton P. T., Li L., Zhou B., Schweingruber C., Hovorakova M., Xie M., Sun X., Sandhow L., Artemov A. V., Ivashkin E., Suter S., Dyachuk V., El Shahawy M., Gritli-Linde A., Bouderlique T., Petersen J., Mollbrink A., Lundeberg J., Enikolopov G., Qian H., Fried K., Kasper M., Hedlund E., Adameyko I., Sävendahl L., Chagin A.S. A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate. Nature. 2019. DOI: 10.1038/s41586-019-0989-6
Soldatov R., Kaucka M., Kastriti M. E., Petersen J., Chontorotzea T., Englmaier L., Akkuratova N., Yang Y., Häring M., Dyachuk V., Bock C., Farlik M., Piacentino M. L., Boismoreau F., Hilscher M. M., Yokota C., Qian X., Nilsson M., Bronner M. E., Croci L., Hsiao W. Y., Guertin D. A., Brunet J. F., Consalez G. G., Ernfors P., Fried K., Kharchenko P. V., Adameyko I. Spatiotemporal structure of cell fate decisions in murine neural crest. Science. 2019. DOI: 10.1126/science.aas9536.
Smolina N., Khudiakov A., Knyazeva A., Zlotina A., Sukhareva K., Kondratov K., Gogvadze V., Zhivotovsky B., Sejersen T., Kostareva A. Desmin mutations result in mitochondrial dysfunction regardless of their aggregation properties. Biochim Biophys Acta Mol Basis Dis. 2020; 24:165745. doi: 10.1016/j.bbadis.2020.165745. IF 4.352
Perepelina K., Klauzen P., Khudiakov A., Zlotina A., Fomicheva Y., Rudenko D., Gordeev M., Sergushichev A., Malashicheva A., Kostareva A. Generation of two iPSC lines (FAMRCi006-A and FAMRCi006-B) from patient with dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy associated with genetic variant LMNAp.Arg527Pro. Stem Cell Res. 2020; 43:101714. doi: 10.1016/j.scr.2020.101714. IF 4.489
Khudiakov A., Perepelina K., Klauzen P., Zlotina A., Gusev K., Kaznacheyeva E., Malashicheva A., Kostareva A. Generation of two iPSC lines (FAMRCi004-A and FAMRCi004-B) from patient with familial progressive cardiac conduction disorder carrying genetic variant DSP p.His1684Arg. Stem Cell Res. 2020; 43:101720. doi: 10.1016/j.scr.2020.101720. IF 4.489
A. Malashicheva, A. Kostina, A. Kostareva, O. Irtyuga, M. Gordeev and V. Uspensky (2020). “Notch signaling in the pathogenesis of thoracic aortic aneurysms: A bridge between embryonic and adult states.” Biochim Biophys Acta Mol Basis Dis 1866(3): 165631. https://doi.org/10.1016/j.bbadis.2019.165631 IF 4,3 Q1
Aquila G., Kostina A., Vieceli Dalla Sega F., Shlyakhto E., Kostareva A., Marracino L., Ferrari R., Rizzo P., Malaschicheva A 2019 The Notch pathway: a novel therapeutic target for cardiovascular diseases? Expert Opin Ther Targets 23:695–710. https://doi.org/10.1080/14728222.2019.1641198 IF 4,6, Q1
Klauzen P., Perepelina K., Khudiakov A., Zlotina A., Fomicheva Y., Pervunina T., Vershinina T., Kostareva A., Malashicheva A. Generation of two induced pluripotent stem cell lines (FAMRCi005-A and FAMRCi005-B) from patient carrying genetic variant LMNA p.Asp357Val. Stem Cell Res. 2020; 43:101719. doi: 10.1016/j.scr.2020.101719. IF 4.489
Olmastroni E., Tragni E., Casula M., Shlyakhto E. V., Konradi A. O., Rotar O. P., Alieva A. S., Boyarinova M. A., Baragetti A., Catapano A. L., Grigore L., Pellegatta F. Epidemiology Of Cardiovascular Risk Factors In Two Population-based Studies // Atherosclerosis, Supplements. 2018. Т. 35. С. e14-e20.

Patents and inventions

Contacts

Elena Vasichkina, Head of the Department
tel.: +7 (921) 935-18-90
e-mail: Vasichkina_ES@almazovcentre.ru