Laboratory of Epigenetics

At present, molecular basis of hereditary pathology is the most intensively studied problem in medical and molecular genetics.  Recent achievements in this field of science demonstrate that unraveling the nucleotide sequences is no more than one of the first steps towards understanding the natural laws of functioning of the genome as a whole. Studies of normal and abnormal structural and functional characteristics of chromosome regions, DNA modifications and functions of “gene concerts” become one of leading fields of research.  

Imprinting phenomenon, position effect and structural and functional chromatin organization within the specific chromosome region predetermine the patterns of gene expression. Changes in gene expression without structural alterations in its nucleotide sequence are classified as epigenetic ones.  Mechanisms of these disorders include abnormal methylation of promoter and regulatory regions of genes, dynamic (amplification of microsatellite repeats) and point mutations in the regulatory regions, transpositions of repetitive genomic elements.  The contribution of epigenetic regulation of gene activity based on the abnormal methylation of promoter CpG islands leading to their inactivation has been considered recently one of causes of a number of genetic diseases and cancer.

One of the main fields of research in the Laboratory includes studies of structural and functional organization of the chromosome regions whose alterations lead to syndromic forms of multiple congenital defects.  Special attention is paid to microdeletion syndromes and diseases associated with imprinting and dynamic mutations. Characterization of the range of molecular pathology and development of the diagnostic protocols is carried out in this field.

Another field of research is related to molecular mechanisms of carcinogenesis and, first of all, assessment of epigenetic mechanisms of gene expression regulation. Most attention is paid to the search for and characterization of molecular markers with potential diagnostic and prognostic relevance.  We consider several principal aspects: molecular diagnostics of hereditary forms of cancer, identification and characterization of poor prognostic markers, micrometastases diagnostics, search for and characterization of carcinogenesis markers detectable presymptomatically. Diagnostic protocols allowing improvements in diagnostic quality and treatment efficiency are the main results of this research. Studies of stromal-mesenchymal interactions, clonal origin of tumors and their relapses are carried out within this field of research.

The third field of the research is related to the analysis of polymorphic DNA variants that increase the risk of wide-spread diseases including cancers. Besides, studies of DNA polymorphisms that determine the effects of medications are also carried out.  Results of these studies may and can improve the quality of life and public health.

The search for genetic causes of male and female infertility, in particular, characterization of polymorphic DNA variants complicating pregnancy, characterization of nonrandom X chromosome inactivation, etc. os one more field of research. Studies of aneuploidies and epigenetic abnormalities are carried out at the early stages of development (pre-blastocyst) of embryos and in cases of early pregnancy losses.

1. Dantsev IS, Ivkin EV, Tryakin AA, Godlevski DN, Latyshev OY, Rudenko VV, Mikhaylenko DS, Chernykh VB, Volodko EA, Okulov AB, Loran OB, Nemtsova MV. Genes associated with testicular germ cell tumors and testicular dysgenesis in patients with testicular microlithiasis // Asian Journal of Andrology. - 2018. [Epub ahead of print] doi: 10.4103/aja.aja_54_18.
2. D.S. Mikhaylenko, B.Y. Alekseev, D.V. Zaletaev, R.I. Goncharova, M.V. Nemtsova. Structural Alterations in Human Fibroblast Growth Factor Receptors in Carcinogenesis // Biochemistry (Moscow). – 2018. - Vol. 83. - No. 8. - pp. 930-943.
3. Tanas A.S., Borisova M.E., Kuznetsova E.B., Rudenko V.V., Karandasheva K.O., Nemtsova M.V., Izhevskaya V.L., Simonova O.A., Larin S.S., Zaletaev D.V., Strelnikov V.V. Rapid and affordable genome-wide bisulfite DNA sequencing by XmaI-reduced representation bisulfite sequencing //Epigenomics. – 2017. - Vol. 9, No. 6, P. 833-847.
4. Dmitry S. Mikhaylenko, Gennady D. Efremov, Vladimir V. Strelnikov, Dmitry V. Zaletaev, Boris Y. Alekseev. Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer // Current Genomics. – 2017. –№ 18. – P. 236-243.
5. Marina V. Nemtsova, Vladimir V. Strelnikov, Alexander S. Tanas, Igor I. Bykov, Dmitry V. Zaletaev, Viktoria V. Rudenko, Alexander I. Glukhov, Tatiana V. Kchorobrich, Yi Li, George E. Barreto, Gjumrakch Aliev. Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice //Current Genomics. – 2017. №18. –P. 408-415.
6. Alekseeva, E. A., Kuznetsova, E. B., Tanas, A. S., Prozorenko, E. V., Zaytsev, A. M., Kurzhupov, M. I., Kirsanova, O. N., Rudenko, V.V., Strelnikov, V.V., Zaletaev, D. V. Loss of Heterozygosity and Uniparental Disomy of Chromosome Region 10q23. 3–26.3 in Glioblastoma //Genes, Chromosomes and Cancer. – 2017. – V. 57. - № 1. P. 42-47.
7. Inna V. Zolnikova, Vladimir V. Strelnikov, Natalia A. Skvortsova, Alexander S. Tanas, Debmalya Barh, Elena V. Rogatina, Irina V. Egorova, Darja V. Levina, Olga N. Demenkova, Egor G. Prikaziuk, Marianna E. Ivanova. Stargardt disease-associated mutation spectrum of a Russian Federation cohort //European Journal of Medical Genetics. – 2017. – V. 60. – P. 140-147.
8. Mikhailenko, D. S., Efremov, G. D., Safronova, N. Y., Strelnikov, V. V., Alekseev, B. Y. Detection of Rare Mutations by Routine Analysis of KRAS, NRAS, and BRAF Oncogenes //Bulletin of experimental biology and medicine. – 2017. – Т. 162. – №. 3. – P. 375-378.
9. Kekeeva T. Tanas, A., Kanygina, A., Alexeev, D., Shikeeva, A., Zavalishina, L., Andreeva, Y., Frank, G., Zaletaev, D. Novel fusion transcripts in bladder cancer identified by RNA-seq //Cancer letters. – 2016. – V. 374. – №. 2. – P. 224-228.
10. Golovastova M. O., Tsoy, L. V., Bocharnikova, A. V., Korolev, D. O., Gancharova, O. S., Alekseeva, E. A., Kuznetsova E.B., Savvateeva L.V., Skorikova E.E., Strelnikov V.V., Varshavsky, V. A., Vinarov A.Z., Nikolenko V.N., Glybochko P.V., Zernii E.Yu., Zamyatnin Jr. A.A., Bazhin A.V., Philippov P.P. The cancer-retina antigen recoverin as a potential biomarker for renal tumors //Tumor Biology. – 2016. – V. 37. - № 7. – P. 9899-9907.
11. Imyanitov E.N., Demidova I.A., Gordiev M.G., Filipenko M.L., Kekeyeva T.V., Moliaka Y.K., Gervas P.A., Kozhemyako V.B., Vodolazhskiy D.I., Sergeyeva L.A., Fattakhova D., Iyevleva A.G., Mitiushkina N.V., Kuligina E.Sh., Barinov A.A., Mommaeva M.S., Aleksakhina S.N., Tsimafeyeu I.V., Tjulandin S.A. Distribution of EGFR Mutations in 10,607 Russian Patients with Lung Cancer // Molecular diagnosis & therapy. – 2016. –Vol. 20. - № 4, P. 401-406.
12. Frank, G. A., Aleksakhina, S. N., Zavalishina, L. E., Kekeyeva, T. V., Venina, A. R., Ivantsov, A. O., ... Imyanitov, E. N. (2016). BRAF and NRAS mutations in Russian melanoma patients: results of a nationwide study //Melanoma Research. – 2016. – V. 26. – №. 5. – P. 442-447.
13. Simonova, O. A., Kuznetsova, E. B., Poddubskaya, E. V., Kekeeva, T. V., Kerimov, R. A., Trotsenko, I. D., Tanas, A. S., Rudenko V. V., Alekseeva, E. A., Zaletaev, D.V, Strelnikov, V. V. DNA methylation in the promoter regions of the laminin family genes in normal and breast carcinoma tissues //Molecular Biology. – 2015. – V. 49. – №. 4. – P. 598-607.
14. Tanas, A. S., Kuznetsova, E. B., Borisova, M. E., Rudenko, V. V., Zaletayev, D. V., & Strelnikov, V. V. Reduced representation bisulfite sequencing design for assessing the methylation of human CpG islands in large samples //Molecular Biology. – 2015. – V. 49. – №. 4. – P. 618-626.
15. Alexander S Tanas, Viktoria V Shkarupo, Ekaterina B Kuznetsova, Dmitry V Zaletayev, Vladimir V Strelnikov. Novel tools for unbiased DNA differential methylation screening //Epigenomics, 2010, Vol. 2, No. 2, Pages 325-333
16. EB Kuznetsova, TV Kekeeva, SS Larin, VV Zemlyakova, AV Khomyakova, OV Babenko, MV Nemtsova, DV Zaletayev, VV Strelnikov. Methylation of the BIN1 gene promoter CpG island associated with breast and prostate cancer // J Carcinog. – Jan 2007. – №6. – P.9.
17. Klinkov A.A., Strelnikov V.V., Babenko O.V., Zemlyakova V.V., Zaletayev D.V., Ivanov M.A., Kuznetsova E.B., Nikitin E.A., Maiorova O.V. TNR/11q#1 Trinucleotide (GCC)n Repeat Alleles and Predisposition to Acute and Chronic Leukemia // Annals of Human Genetics, 2004. V. 68. № 4. P. 362-366.
18. Strelnikov V.V., Nemtsova M.V., Chesnokova G.G., Kuleshov N.P., Zaletayev D.V. A simple multiplex FRAXA, FRAXE and FRAXF PCR assay convenient for wide screening programs // Human Mutation. – 1999. – № 2. – P.166–169.

Theses:

1. Alekseeva Ekaterina Aleksandrovna, 2015: “Structural and epigenetic disorders of the human genome with glioblastoma”, Candidate of biological sci., 03.02.07 - genetics
2. Shikeeva Amulang Alekseevna, 2014: “Molecular genetic changes in non-small cell lung cancer”, Candidate of medical sci. 03.02.07 - genetics, January 14, 2012 - oncology
3. Babayan Anna Yuryevna, 2013: “Analysis of molecular genetic disorders in the bladder cancer genesis”, Candidate of biol. sci. 03.02.07 - genetics
4. Strelnikov Vladimir Viktorovich, 2012: "A comprehensive study of the methylotypes of malignant neoplasms: fundamental and applied aspects", Doctor of Biological Science, 03.02.07 - Genetics
5. Rudenko Victoria Vladimirovna, 2012: “New markers of abnormal DNA methylation in breast cancer, identified by unbiased screening of differential genome methylation”, Candidate of biol. sci., 03.02.07 - genetics
6. Tanas Alexander Sergeevich, 2012: “Analysis of differential methylation of genomes by unbiased screening methods”, Candidate of biol. sci., 03.02.07 - genetics, 03.01.09 - mathematical biology, bioinformatics
7. Manokhina Irina Konstantinovna, 2009: “Characterization of molecular pathology in uveal melanomas”, Candidate of medical science, 03.02.07 - genetics
8. Kuznetsova Ekaterina Borisovna, 2006: “Identification and characterization of new markers of the genes methylation and expression involved in carcinogenesis in breast cancer”, Candidate of biol. sci., 03.00.15 - genetics
9. Zemlyakova Valeria Vladimirovna, 2003: “Research on methylation of a number of genes involved in carcinogenesis in various types of tumors”, Candidate of biol. sci., 03.00.15 - genetics
10. Nemtsova Marina Vyacheslavovna, 2002: "Disorders in the epigenetic regulation of gene expression as a new class of molecular pathology", Doctor of Biological Sciences, 03.00.15 - Genetics
11. Babenko Olga Vladimirovna, 2001: “Characterization of the molecular pathology spectrum in retinoblastoma and development of a DNA diagnostic protocol”, Candidate of biol. sci., 03.00.15 - genetics
12. Strelnikov Vladimir Viktorovich, 2000: "Study of structural and functional disorders of the X chromosome, leading to various forms of X-linked mental retardation", Candidate of biol. sci., 03.00.15 - genetics

1. Алексеева Екатерина Александровна, 2015 г.: «Структурные и эпигенетические нарушения генома человека при глиобластоме», к.б.н., 03.02.07 – генетика
2. Шикеева Амуланг Алексеевна, 2014 г.: «Молекулярно-генетические изменения при немелкоклеточном раке легкого», к.м.н., 03.02.07 – генетика, 14.01.12 – онкология
3. Бабаян Анна Юрьевна, 2013 г.: «Анализ молекулярно-генетических нарушений в генезе рака мочевого пузыря», к.б.н., 03.02.07 – генетика
4. Стрельников Владимир Викторович, 2012 г.: «Комплексное исследование метилотипов злокачественных новообразований: фундаментальные и прикладные аспекты», д.б.н., 03.02.07 – генетика
5. Руденко Виктория Владимировна, 2012 г.: «Новые маркеры аномального метилирования ДНК при раке молочной железы, идентифицированные непредвзятым скринингом дифференциального метилирования геномов», к.б.н., 03.02.07 – генетика
6. Танас Александр Сергеевич, 2012 г.: «Анализ дифференциального метилирования геномов методами непредвзятого скрининга», к.б.н., 03.02.07 – генетика, 03.01.09 – математическая биология, биоинформатика
7. Манохина Ирина Константиновна, 2009 г.: «Характеристика молекулярной патологии в увеальных меланомах», к.м.н., 03.02.07 – генетика
8. Кузнецова Екатерина Борисовна, 2006 г.: «Идентификация и характеристика новых маркеров метилирования и экспрессии генов, вовлеченных в канцерогенез, при раке молочной железы», к.б.н., 03.00.15 – генетика
9. Землякова Валерия Владимировна, 2003 г.: «Исследование метилирования ряда генов, вовлеченных в канцерогенез, в различных типах опухолей», к.б.н., 03.00.15 - генетика
10. Немцова Марина Вячеславовна, 2002 г.: «Нарушения эпигенетической регуляции экспрессии генов как новый класс молекулярной патологии», д.б.н., 03.00.15 - генетика
11. Бабенко Ольга Владимировна, 2001 г.: «Характеристика спектра молекулярной патологии при ретинобластоме и разработка ДНК-диагностического протокола», к.б.н., 03.00.15 - генетика
12. Стрельников Владимир Викторович, 2000 г.: «Изучение структурных и функциональных нарушений Х-хромосомы, приводящих к различным формам Х-сцепленной умственной отсталости», к.б.н., 03.00.15 - генетика

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3. МИА - Медицинское информационное агентство. 15.01.2019 г. Генетика на страже здоровья россиян.
4. Московский комсомолец. 22.01.2019.  Московские врачи научились предсказывать эффективность химиотерапии при раке молочной железы.
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7. ТАСС наука. 27.06. 2020 г. Ученые выяснили, как предсказать итоги предоперационной химиотерапии рака груди.
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11. Пресс-центр МГНЦ. 28.10.2020 г. Владимир Стрельников принял участие в Лекториуме РНФ в рамках всероссийского фестиваля NAUKA 0+.
12. Лекторий фестиваля Наука 0+. 10.10.2021 г. Эпигенетический портрет раковой опухоли: как ученые изучают рак и какие инструменты они дают врачам для победы над болезнью.