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Шкурников Максим Юрьевич

Факультет биологии и биотехнологии

Профиль на hse.ru ↗ тел.: + 7 (495) 772-95-90 | 15261
Публикаций
38
Языков
1
Наград
8
Конференций
0
Профиль Публикации (38) Курсы (4)

Профессиональные интересы

молекулярная биологиябиохимиябиоинформатика

Должности

  • Заведующий лабораторией — Факультет биологии и биотехнологии, Лаборатория исследований молекулярных механизмов долголетия
  • Ведущий научный сотрудник — Факультет биологии и биотехнологии, Лаборатория исследований молекулярных механизмов долголетия
  • Профессор — Факультет биологии и биотехнологии, Базовая кафедра Института биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН

Био

  • · Начал работать в НИУ ВШЭ в 2020 году.
  • · Научно-педагогический стаж: 5 лет.

Образование

  • 2024 · Доктор медицинских наук
  • 2009 · Кандидат медицинских наук
  • 2004 · Специалитет: Российский государственный медицинский университет Федерального агентства по здравоохранению и социальному развитию, специальность «Медицинская кибернетика», квалификация «Врач-кибернетик»

Опыт работы

  • · 2004: Август ‒ июнь
  • · 2006: : научный сотрудник, лаборатория ксенотрансплантации, Институт трансплантологии и искусственных органов
  • · 2006: Июль ‒ февраль
  • · 2011: : старший научный сотрудник, лаборатории молекулярной физиологии, Российский научно-исследовательский институт спорта и физического воспитания
  • · 2011: Февраль ‒ Январь
  • · 2014: : ведущий научный сотрудник, лаборатория молекулярной физиологии, Институт общей патологии и патофизиологии РАМН
  • · 2014: Февраль ‒ декабрь
  • · 2017: : старший научный сотрудник, отдел трансляционной онкологии, Московский научно-исследовательский онкологический институт имени П. А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России
  • · 2018: Январь ‒ ноябрь
  • · 2020: : начальник отдела трансляционной онкологии, Московский научно-исследовательский онкологический институт имени П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России
  • · 2020: Декабрь ‒ настоящее время: Факультет биологии и биотехнологии НИУ ВШЭ

Награды и поощрения

  • · Благодарность Министерства науки и высшего образования Российской Федерации (декабрь 2024)
  • · Благодарность проректора НИУ ВШЭ (ноябрь 2024)
  • · Благодарность Факультета биологии и биотехнологии НИУ ВШЭ (февраль 2023)
  • · Надбавка за публикации, вносящие особый вклад в международную научную репутацию НИУ ВШЭ (2022–2025)
  • · Надбавка за публикацию в международном рецензируемом научном издании (2021–2022)
  • · Надбавка за регулярные публикации в международных рецензируемых научных изданиях (2025–2030)
  • · Победитель Конкурса лучших русскоязычных научных и научно-популярных работ работников НИУ ВШЭ – 2024, 2022
  • · Лучший академический руководитель в номинации «Прием иностранных студентов» — 2024

Гранты и проекты

  • — · на соискание учёной степени кандидата наук

Идентификаторы исследователя

Публикации (38)

Differences in the Drosha and Dicer Cleavage Profiles in Colorectal Cancer and Normal Colon Tissue Samples

2020 · ARTICLE · en

Human colorectal adenocarcinoma cell line Caco-2 is often used as a model of healthy intestinal epithelium, in particular, in miRNA studies. The work of the enzymes Drosha and Dicer is an integral part of the process of miRNA formation. Inaccuracies in the work of these enzymes lead to a change in the nucleotide sequences of miRNAs with the formation of new isoforms, which, in turn, can change intracellular regulatory mechanisms. In the framework of this study, it was shown that the quantitative estimates of inaccuracies in Drosha and Dicer activity significantly differ between the specimens of normal colon tissue and malignant colorectal tumors.

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Factors Involved in miRNA Processing Change Its Expression Level during Imitation of Hypoxia in BeWo b30 Cells

2020 · ARTICLE · en

One of the main complications of pregnancy and causes of maternal and perinatal mortality is preeclampsia. The pathophysiology of preeclampsia is associated with the development of placenta and fetal hypoxia and secretion of a number of effective molecules. The human choriocarcinoma cell line BeWo b30 is often used as a model of the placental barrier. It was shown that oxyquinoline derivatives can mimic hypoxia by suppressing HIF-prolyl hydroxylases and the accumulation of HIF-1α. This effect also leads to a change in the expression of microRNAs and their target genes. However, with hypoxia in cells, not only the level of individual miRNAs but also the ratio of miRNA isoforms (isomiRs) can change, presumably due to inaccuracies in the work of the Drosha and Dicer enzymes. In this work, we showed a change in the expression of the factors involved in the maturation of miRNAs when simulating hypoxia in BeWo b30 cells with an oxyquinoline derivative, which may be one of the causes for the change in the ratio of miRNA isoforms.

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Detection of Low-Abundant MicroRNAs with Hybridization Microchips

2019 · ARTICLE · en

The effect of low concentrations of miRNA on the ability of GeneChip miRNA 4.0 hybridization chips to evaluate their representation in the sample was studied. It is shown that the evaluation of the expression of 61 miRNAs is statistically significantly associated with the multiplicity of plasma dilution. Only 12 miRNAs showed very high Pearson correlation coefficient (>0.95) and they all decreased in response to dilution. High abundance of has-miR-4532 miRNA in plasma was demonstrated. This miRNA was never detected during sequencing of similar samples. It was concluded that in case of miRNA expression

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Human Platelet Lysate Sustains the Osteogenic/Adipogenic Differentiation Potential of Adipose-Derived Mesenchymal Stromal Cells and Maintains Their DNA Integrity in vitro

2019 · ARTICLE · en

Human platelet lysate (HPL) is a promising alternative to fetal calf serum (FCS) for the expansion of adipose tissue mesenchymal stromal cells (AT-MSCs) for translational medicine applications. However, some biological effects of HPL are still to be elucidated. We aimed to compare complex characteristics, such as cell morphology, proliferative activity, differentiation potential, and especially monolayer recovery, DNA integrity, and the gene expression pattern, between AT-MSCs cultured with HPL or FCS. Primary AT-MSC cultures were expanded in medium containing FCS or pooled HPL. Cell growth and proliferation were estimated by cell doubling time and the monolayer formation rate, while migration was assessed by wound-healing assay. The capacity for adipogenic and osteogenic differentiation was evaluated by alkaline phosphatase and Oil Red O staining. DNA integrity was evaluated by comet assay, and analysis of gene expression by real-Time PCR. Media supplemented with HPL or FCS provided a similar surface immunophenotype, cell morphology (except some cell dimensions and a bigger colony size in HPL), DNA integrity, and rate of wound healing. Meanwhile, AT-MSC proliferated more intensively in HPL-supplemented media (especially at 5% HPL) and had a reduced doubling population time. AT-MSC in HPL had increased adipogenic potential and similar osteogenic potential in comparison with FCS. Our results indicate the feasibility and evident prospects for the use of pooled HPL as an alternative to FCS and safe non-xenogenic growth supplement for ex vivo expansion of clinical-grade AT-MSCs for regenerative medicine purposes.

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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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Comprehensive network of miRNA-induced intergenic interactions and a biological role of its core in cancer

2018 · ARTICLE · en

MicroRNAs (miRNAs) are a family of short noncoding RNAs that posttranscriptionally regulate gene expression and play an important role in multiple cellular processes. A significant percentage of miRNAs are intragenic, which is often functionally related to their host genes playing either antagonistic or synergistic roles. In this study, we constructed and analyzed the entire network of intergenic interactions induced by intragenic miRNAs. We further focused on the core of this network, which was defined as a union of nontrivial strongly connected components, i.e., sets of nodes (genes) mutually connected via directed paths. Both the entire network and its core possessed statistically significant non-random properties. Specifically, genes forming the core had high expression levels and low expression variance. Furthermore, the network core did not split into separate components corresponding to individual signalling or metabolic pathways, but integrated genes involved in key cellular processes, including DNA replication, transcription, protein homeostasis and cell metabolism. We suggest that the network core, consisting of genes mutually regulated by their intragenic miRNAs, could coordinate adjacent pathways or homeostatic control circuits, serving as a horizontal inter-circuit link. Notably, expression patterns of these genes had an efficient prognostic potential for breast and colorectal cancer patients.

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Knockdown of L1CAM significantly reduces metastasis in a xenograft model of human melanoma: L1CAM is a potential target for anti-melanoma therapy

2018 · ARTICLE · en

Finding additional functional targets for combination therapy could improve the outcome for melanoma patients. In a spontaneous metastasis xenograft model of human melanoma a shRNA mediated knockdown of L1CAM more than sevenfold reduced the number of lung metastases after the induction of subcutaneous tumors for two human melanoma cell lines (MeWo, MV3). Whole genome expression arrays of the initially L1CAM high MeWo subcutaneous tumors revealed unchanged or downregulated genes involved in epithelial to mesenchymal transition (EMT) except an upregulation of Jagged 1, indicating a compensatory change in Notch signaling especially as Jagged 1 expression showed an increase in MeWo L1CAM metastases and Jagged 1 was expressed in metastases of the initially L1CAM low MV3 cells as well. Expression of 17 genes showed concordant regulation for L1CAM knockdown tumors of both cell lines. The changes in gene expression indicated changes in the EMT network of the melanoma cells and an increase in p53/p21 and p38 activity contributing to the reduced metastatic potential of the L1CAM knockdowns. Taken together, these data make L1CAM a highly interesting therapeutic target to prevent further metastatic spread in melanoma patients.

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Panel of 6 microRNAs for minimally invasive diagnosis of prostate cancer

2017 · ARTICLE · en

INTRODUCTION AND OBJECTIVES: Routine screening of prostate cancer (PC) based on serum prostate-specific antigen detection and digital rectal examination has modest positive and negative predictive value. The aim of represented study was to identify a panel of plasma microRNAs (miRNAs) for minimally invasive diagnosis of PC. METHODS: During 2014-2015, 245 patients participated in the cross-sectional study. The Group 1 consisted of 188 patients with histologically confirmed PC. The Group 2 consisted of 57 patients including healthy individuals and patients with benign prostatic hyperplasia, urinary system diseases or anomalies, bladder or renal cancer. Plasma miRNAs profiles was studied with aid of GeneChip’ miRNA 4.0 Arrays (Affymetrix, USA) comprising probe set for 2,578 human mature miRNAs. All miRNAs with the 3rd quartile of Bi-weight Average Signal (log2) less than 1,49 were excluded from the analysis just as miRNAs with signal correlating with hemoglobin level as hemolysis sign (p-value RESULTS: Diagnostic significance was demonstrated even for pairs of miRNAs. In particular best pair consisting of hsa-miR155-5p and hsa-miR-619-5p allowed achieving 80.7% sensitivity at 69.2% specificity (AUC 0.817). Triplets of miRNAs showed better accuracy, e.g. for triplet hsa-miR-155-5p, hsa-miR-619-5p, and hsamiR-6777-5p sensitivity was 78.9% while specificity was 80.8% (AUC 0.850). The best triplet hsa-miR-6085, hsa-miR-6511b-5p, and hsa-miR-6886-5p allowed achieving 81.3% sensitivity at 80.8% specificity (AUC 0.860). For diagnostic panel consisting of all 6 miRNAs sensitivity reached 83.7% at specificity 84.6% (AUC 0.913). CONCLUSIONS: These results show high diagnostic potential of the panel of 6 circulating miRNAs (hsa-miR-155-5p, hsa-miR-619-5p, hsa-miR-6777-5p, hsa-miR-6085, hsa-miR-6511b-5p, and hsa-miR6886-5p) for minimally invasive diagnosis of prostate cancer which may improve the diagnostic accuracy of modern PC screening.

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Курсы (4)