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Никулин Сергей Вячеславович

Аспирантская школа по биологии

Профиль на hse.ru ↗ тел.: 15093
Публикаций
37
Языков
1
Наград
6
Конференций
2
Профиль Публикации (37) Курсы (9)

Профессиональные интересы

модель кишечника человека in vitroонкологияперсонифицированная медицинабиоинформатикамолекулярная биологиябиология ракаклеточная биология3-х мерные клеточные моделибиохимия

Должности

  • Академический директор — Аспирантская школа по биологии
  • Доцент — Факультет биологии и биотехнологии, Базовая кафедра Института биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН
  • Старший научный сотрудник — Факультет биологии и биотехнологии, Лаборатория исследований молекулярных механизмов долголетия
  • Ведущий научный сотрудник — Факультет биологии и биотехнологии, Международная лаборатория микрофизиологических систем

Био

  • · Начал работать в НИУ ВШЭ в 2020 году.

Образование

  • 2020 · Кандидат биологических наук: Московский физико-технический институт (национальный исследовательский университет)
  • 2019 · Аспирантура: Московский физико-математический институт (государственный университет), специальность «Биологические науки», квалификация «Исследователь. Преподаватель-исследователь»
  • 2015 · Магистратура: Московский физико-технический институт (национальный исследовательский университет), специальность «Прикладная математика и физика», квалификация «Магистр прикладной математики и информатики»
  • 2013 · Бакалавриат: Московский физико-технический институт (национальный исследовательский университет), специальность «Прикладная математика и физика», квалификация «Бакалавр»

Опыт работы

  • · 2020: НИУ ВШЭ с года

Награды и поощрения

  • · Благодарность Министерства науки и высшего образования Российской Федерации (декабрь 2024)
  • · Надбавка за публикации, вносящие особый вклад в международную научную репутацию НИУ ВШЭ (2024–2027)
  • · Надбавка за публикацию в журнале из Списка А (и приравненном к нему научном издании) (2023–2024)
  • · Надбавка за публикацию в международном рецензируемом научном издании (2022–2023, 2021–2022, 2020–2021)
  • · Лучший преподаватель — 2023–2025
  • · Победитель Конкурса лучших русскоязычных научных и научно-популярных работ работников НИУ ВШЭ – 2023

Гранты и проекты

  • — · на соискание учёной степени кандидата наук

Конференции (2)

Показать все
  • · 2019: International Federation of Placenta Associations 2019 (IFPA2019); 8th Latin American Symposium on Maternal-Fetal Interaction and Placenta (VIII SLIMP), Buenos Aires, Argentina (Buenos Aires). Доклад: Application of impedance spectroscopy for analysis of BeWo clone b30 human choriocarcinoma cell line
  • · 2019: 22st European Congress on Alternatives to Animal Testing, 19th Annual Congress of EUSAAT, Linz, Austria (Linz). Доклад: Placenta-on-a-chip model for assessing the transport and toxicity of xenobiotics in vitro

Идентификаторы исследователя

Публикации (37)

Changes in the Metastatic Properties of MDA-MB-231 Cells after IGFBP6 Gene Knockdown Is Associated with Increased Expression of miRNA Genes Controlling INSR, IGF1R, and CCND1 Genes

2019 · ARTICLE · en

Metastatic cascade is associated with the process of epithelial-mesenchymal transition accompanied by changes in cell proliferation, migration, adhesion, and invasiveness mediated by the insulin-like growth factor (IGF) signal pathway. IGFBP6 protein binds IGF and prevents its interaction with receptors. IGFBP6 gene knockdown through RNA-interference inhibits cell migration and increased the rate of proliferation of breast cancer MDA-MB-231 cells. IGFBP6 knockdown cells are characterized by increased expression of MIR100 and MIRLET7A2 genes encoding hsa-miR-100-3p, hsa-miR-100-5p, hsa-let-7a-5p, and hsa-let-7a-2-3p miRNA. The target genes of these microRNAs are IGF2, IGF1R, INSR, and CCND1 associated with IGF signaling pathway and proliferative and migratory activity during the metastatic cascade. A significant decrease in the expression of INSR and CCND1 genes was demonstrated by PCR and microarray analysis.

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LAMA4-Regulating miR-4274 and Its Host Gene SORCS2 Play a Role in IGFBP6-Dependent Effects on Phenotype of Basal-Like Breast Cancer

2019 · ARTICLE · en

Specificity of RNAi to selected target is challenged by off-target effects, both canonical and non-canonical. Notably, more than half of all human microRNAs are co-expressed with hosting them proteincoding genes. Here we dissect regulatory subnetwork centered on IGFBP6 gene, which is associated with low proliferative state and high migratory activity of basal-like breast cancer. We inhibited expression of IGFBP6 gene in a model cell line for basal-like breast carcinoma MDA-MB-231, then traced secondary and tertiary effects of this knockdown to LAMA4, a laminin encoding gene that contributes to the phenotype of triple-negative breast cancer. LAMA4-regulating miRNA miR-4274 and its host gene SORCS2 were highlighted as intermediate regulators of the expression levels of LAMA4, which correlated in a basal-like breast carcinoma sample subset of TCGA to the levels of SORCS2 negatively. Overall, our study points that the secondary and tertiary layers of regulatory interactions are certainly underappreciated. As these types of molecular event may significantly contribute to the formation of the cell phenotypes after RNA interference based knockdowns, further studies of multilayered molecular networks affected by RNAi are warranted.

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Transport and toxicity of 5-fluorouracil, doxorubicin, and cyclophosphamide in in vitro placental barrier model based on BeWo b30 cells

2019 · ARTICLE · en

An in vitro placental barrier model based on human choriocarcinoma BeWo b30 cell line was considered as a method of preclinical study of the transport and toxicity of antitumor agents and other organic compounds. Low permeabilities were found for 5-fluorouracil as an example of hydrophilic compound and for doxorubicin as an example of a lipophilic compound with a high degree of binding to proteins and DNA and a high permeability was found for cyclophosphamide as an example of lipophilic compound with a low degree of binding to proteins. Using impedance spectrometry and cell viability assessment via reduction of resazurin to resorufin, a pronounced cytotoxic effect of doxorubicin and good tolerance of 5-fluorouracil and cyclophosphamide by the cells were shown for drug concentrations equal to the maximum concentrations in the patients’ blood during the treatment of breast cancer.

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Application of impedance spectroscopy for analysis of BeWo clone b30 human choriocarcinoma cell line

2019 · ARTICLE · en

Objectives: BeWo cells are used for the construction of in vitro models of placental barrier. Only the early placenta possesses multiple trophoblast layers whereas third-trimester placenta consists of a single trophoblast layer. BeWo cells do not undergo contact growth inhibition and form multilayer structures. It is important to control the cell state for transport experiments. Impedance spectroscopy was applied for electrical characteristic studying during BeWo cell growth and in response to HIF-1 activator. Methods: 30,000 cells per insert were seeded into a 96-well Transwell plate (1 μm pore size). After 48 h a potent HIF-1 activator D014-0021 was added at 10 μM concentration. Impedance spectra were acquired with impedance spectroscopy system (Bioclinicum, Russia). For the extraction of electrical parameters, the equivalent electrical circuits were used. Student's t-test was used to calculate the statistical significance. Results: It was predicted from the mathematical model that medium resistance (Rmed) and the radius of the impedance hodograph (and hence TEER) will rise linearly with the number of layers. In the case of one layer, the radius can rise due to the formation of tight junctions but the Rmed should remain stable, but the data shows increasing TEER and Rmed. There is a statistically significant difference in Rmed between 48 and 96 h. It can be concluded that after 48 h the BeWo cells form multilayer structures. The addition of D014-0021 leads to a slight increase in TEER after 6 h and a significant decrease in TEER and capacitance after 27 h. Conclusion: It was shown that formation of multilayer structures can be readily detected with impedance spectroscopy and hence it can be used for quality control of the in vitro placental models. It is possible to use impedance spectroscopy for detection of additional parameter changes such as electrical capacitance. This work is supported by the Russian Science Foundation (project No. 16-19-10597).

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In vitro and in silico liver models: Current trends, challenges and opportunities

2018 · ARTICLE · en

Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using "liver on a chip" devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. Impediments to the development of "liver on a chip" technology include the problems with standardization of cells, limitations imposed by culturing and the necessity to develop more complicated fluidic contours. Fortunately, recent breakthroughs in the development of cell-based reporters, including ones with fluorescent label, permits monitoring of the behavior of the cells embed into the "liver on a chip" devices. Finally, a set of computational approaches has been developed to model both particular toxic response and the homeostasis of human liver as a whole; these approaches pave a way to enhance the in silico stage of assessment for a potential toxicity.

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Which cytochrome P450 metabolizes phenazepam? Step by step in silico, in vitro, and in vivo studies

2018 · ARTICLE · en

Phenazepam (bromdihydrochlorphenylbenzodiazepine) is the original Russian benzodiazepine tranquilizer belonging to 1,4-benzodiazepines. There is still limited knowledge about phenazepam's metabolic liver pathways and other pharmacokinetic features. To determine phenazepam's metabolic pathways, the study was divided into three stages: In silico modeling, in vitro experiment (cell culture study), and in vivo confirmation. In silico modeling was performed on the specialized software PASS and GUSAR to evaluate phenazepam molecule affinity to different cytochromes. The in vitro study was performed using a hepatocytes' cell culture, cultivated in a microbioreactor to produce cytochrome P450 isoenzymes. The culture medium contained specific cytochrome P450 isoforms inhibitors and substrates (for CYP2C9, CYP3A4, CYP2C19, and CYP2B6) to determine the cytochrome that was responsible for phenazepam's metabolism. We also measured CYP3A activity using the 6-betahydroxycortisol/cortisol ratio in patients. According to in silico and in vitro analysis results, the most probable metabolizer of phenazepam is CYP3A4. By the in vivo study results, CYP3A activity decreased sufficiently (from 3.8 [95% CI: 2.94-4.65] to 2.79 [95% CI: 2.02-3.55], p=0.017) between the start and finish of treatment in patients who were prescribed just phenazepam. Experimental in silico and in vivo studies confirmed that the original Russian benzodiazepine phenazepam was the substrate of CYP3A4 isoenzyme.

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Activation of Nrf2 and Hypoxic Adaptive Response Contribute to Neuroprotection Elicited by Phenylhydroxamic Acid Selective HDAC6 Inhibitors

2018 · ARTICLE · en

Activation of HIF-1α and Nrf2 is a primary component of cellular response to oxidative stress, and activation of HIF-1α and Nrf2 provides neuroprotection in models of neurodegenerative disorders, including ischemic stroke, Alzheimer's and Parkinson's diseases. Screening a library of CNS-targeted drugs using novel reporters for HIF-1α and Nrf2 elevation in neuronal cells revealed histone deacetylase (HDAC) inhibitors as potential activators of these pathways. We report the identification of phenylhydroxamates as single agents exhibiting tripartite inhibition of HDAC6, inhibition of HIF-1 prolyl hydroxylase (PHD), and activation of Nrf2. Two superior tripartite agents, ING-6 and ING-66, showed neuroprotection against various cellular insults, associated with stabilization of both Nrf2 and HIF-1, and expression of their respective target genes in vitro and in vivo. Discovery of the innate ability of phenylhydroxamate HDAC inhibitors to activate Nrf2 and HIF provides a novel route to multifunctional neuroprotective agents and cautions against HDAC6 selective inhibitors as chemical probes of specific HDAC isoform function.

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Курсы (9)