Department : CS » Institute of Cell Biology NAS of Ukraine
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Institute of Cell Biology National Academy of Sciences of Ukraine

 

Department of Cell Signaling

 

Head of Department – Oleh STASYK, PhD, D.Sc., Senior Researcher.

 

Department of Cell Signaling (the name was approved by the Academic Council of the Institute of Biochemistry of the NAS of Ukraine on October 19th, 2000) is the successor of the Department of Biochemistry of Cell Differentiation, established in 1969 as part of the O.V. Palladin Institute of Biochemistry of the AS of Ukraine, since 1974 as a part of the Lviv Department of the O.V. Palladin Institute of Biochemistry of the AS of Ukraine, in 1992 renamed as the Department of Cell Regulatory Systems of the O.V. Palladin Institute of Biochemistry of the NAS of Ukraine. From the moment of its establishment until 1998, the department was headed by the Honored Worker of Science and Technology of Ukraine, Professor Stepan Kusen, and from 1999 to 2006, the head of the department (since 2000 as part of the newly established Institute of Cell Biology of the NAS of Ukraine) was Dr. Lyudmyla Drobot.

 

Department of Cell Signaling (DCS) employs: 1 leading researcher (0.5 part-time position), 3 junior researchers, 1 graduate student and 1 engineer. Since 2007 the employees have defended 5 PhD theses (Vynnytska-Myronovska B., Kurlishchuk Y., Pavlyk Y., Karatsai O., Chen O.) and 1 D.Sc. dissertation (Stasyk O.).

 

DCS conducts international-level research on the development of new approaches to metabolic therapy of malignant tumors based on amino acid starvation. A number of new combined approaches have been proposed, which should make the corresponding therapy more effective and selective. In particular, it was established for the first time in studies conducted during 2007-2025 on a wide range of cell models that:

  1. the level of endogenous enzymes of arginine amino acid biosynthesis in tumor cells of different types does not determine their sensitivity to arginine starvation in vitro in monolayer culture or 3D spheroid culture;
  2. the sensitivity of malignant cells to starvation for individual amino acids is significantly reduced in 3D cultures compared to 2D cultures;
  3. arginine deficiency selectively and significantly inhibits the motility, invasive and clonogenic potential of different types of tumors;
  4. inhibitors of autophagy, proteasomal degradation, inducers of oxidative stress, and inducers of endoplasmic reticulum stress enhance the effect of monotherapy based on arginine deficiency and radiosensitize a number of tumor types;
  5. the plant-derived arginine analogues, canavanine and indospicine, significantly and selectively enhance the proapoptotic potential of metabolic therapy based on arginine deprivation, causing acute endoplasmic reticulum stress and deregulation of a number of cell signaling mechanisms, in particular, the mTOR and MAPK pathways;
  6. indospicine, which accumulates in the biomass of the subtropical legume plant Indigofera spicata, is not subject to degradation by recombinant enzymes-hydrolases human arginase I and bacterial arginine deiminase, which are used in metabolic therapy in clinics.
Testing of combination therapy approaches developed on in vitro cultured cell models in laboratory mouse models with transplanted tumors is in progress.

 

Since 2021, the Department has been actively and successfully developing an applied studies on obtaining monoclonal antibodies to protein-antigens of biotechnological and medical importance using hybridoma technology, which resulted in the implementation of the antibodies obtained in the DCS as part of the rapid lateral flow tests of the company "ХEMA" for the diagnosis of coronavirus (2021) and tuberculosis (2024) pathogens by immunochromatographic analysis, as evidenced by the corresponding acts of implementation.

 

DCS has created a new model of neurodegenerative Parkinson's disease based on recombinant strains of the yeast Ogataea polymorpha, expressing the cytotoxic human alpha-synuclein protein, which is involved in the pathogenesis of this disease. Research has begun on studying the effects of autophagy modulation, exogenous polyamines, metal ions, oxidative stress and other factors on the cytotoxicity of the corresponding protein.

 

In recent years, the Department has initiated research aimed at identifying new informative markers related to the diagnosis, prognosis and monitoring of patients with traumatic brain injury (TBI). A bank of blood plasma samples from patients with TBI is being created. The aim of this work is to create prototypes of rapid tests for TBI that can be used in frontline regions with disrupted medical infrastructure, by military medics and in sports medicine.

 

The Department is equipped with boxes for working with microorganisms and human and animal in vitro cell cultures. DCS also has its own cryobank of pseudonormal and malignantly transformed human and animal cell lines and a collection of model strains of microorganisms (bacteria, yeasts). DCS has its own modernized animal facility, which houses C57Bl/6 and BALB/c mice, allowing studies of the toxicity of various compounds, the effectiveness of antitumor therapy in vivo, and the production of monoclonal antibodies in animals. In recent years, the Department has undergone a significant upgrade to its equipment. From several sources, in particular, due to the funding of the project No. 2023.04/0048 of the National Research Fund of Ukraine, biomedical boxes for sterile work, an automatic hematological analyzer, an inverted microscope, a microplate photometer, laboratory centrifuges, a PCR machine, etc., have been purchased and actively exploited.

Ukrainian | English

Institute of Cell Biology National Academy of Sciences of Ukraine

 

Department of Cell Signaling

 

The main scientific interests of the Department are:

 

  • Search for new approaches to metabolic anticancer therapy, in particular, based on artificial starvation for individual amino acids and combined approaches;

  • Research on natural analogues of amino acids as potential antitumor and antimicrobial agents;

  • Development of new model of Parkinson's disease based on methylotrophic yeasts;

  • Designing stable hybridoma clones and monoclonal antibodies against protein-antigens of biotechnological and medical importance to develop new diagnostic systems.
Ukrainian | English

Institute of Cell Biology National Academy of Sciences of Ukraine

 

Department of Cell Signaling

 

Publications

 

Year Published scientific articles Total impact factor  
All Including articles in the
international journals
2008 3   ___ View publications
2009 5   ___ View publications
2010 3   ___ View publications
2011 11   12.795 View publications
2012 5   13.262 View publications
2013 4   7.464 View publications
2014 5   6.876 View publications
2015 4   8.659 View publications
2016 8 3 12.300 View publications
2017 4 3 13.940 View publications
2018 5 5 17.590 View publications
2019 2 1 10.659 View publications
2020 6 5 22.000 View publications
2021 5 4 30.700 View publications
2022 1   ___ View publication
2023 ___   ___  
2024 4 1 4.500 View publication
2025 3 2 8.800 View publication

2008

 

  1. Stasyk O.G., Maidan M., Stasyk O.V., Van Dijck P., Thevelein J.M., Sibirny A.A. Identification of hexose transporter-like sensor HXS1 and functional hexose transporter HXT1 in the methylotrophic yeast Hansenula polymorpha // Eukaryotic Cell. -2008.- V.7, № 4. – P.735-746.
  2. Ishchuk O.P., Voronovsky A.Y., Stasyk O.V., Gayda G.Z., Gonchar M.V., Abbas C.A., Sibirny A.A. Improvement of xylose high-temperature fermentation in Hansenula polymorpha due to overexpression of the PDC1 gene coding for pyruvate decarboxylase // FEMS Yeast Research. – 2008. – V.8, № 7. – P.1164-1174.
  3. Sybirna N., Brodiak I., Ferents I., Barska M. The effect of L-arginine on the oxidative modification of plasma fibrinogen under experimental diabetes mellitus in rats // Annal. Univers. Mariae Curie-Sklodovska, sectio AA Biologia – 2008. – V. IX,– P. 115-118.

2009

 

  1. Havrylov S., Rzhepetskyy Yu., Malinowska A., Drobot L., Rendowicz M.J. Proteins recruited by SH3 domains of Ruk/CIN85 adaptor identified by LC-MS/MS // Proteome Science.-2009.-Vol. 7, N21.-P. 1-19.
  2. O.I. Basaraba, M.L. Barska, Ya.P. Bobak, H.Yu. Shuvayeva, S.M. Marchenko, V. R. Savran, N.A. Volodko, V.L. Buchman, L.B. Drobot. Expression of (RUK/CIN85)/(CD2AP/CMS) family adapter proteins in human breast adenocarcinoma // Clin. and Experim. Potol.-2009- V. 9, № 4. – P. 125-130.
  3. Rzhepetskyy Y.А., Svinchuk V.V., Buchman V.L.,Drobot L.B. Comparative analysis of Ruk/CIN85 phosphorylation in rat pheochromocytome cell line PC12 under growth factors stimulation// Clinical and eksperimental pathology. 2009.- V. VIII, №2.- p. 64-67.
  4. Brodyak I.V., Zdioruk N.І., Barska M.L., Vovk O.І., Sybirna N.O. Lectincytochemical analysis of mononuclear leukocyte plasmatic membrane sialocontaining glycoprotein of peripheral blood under type 1 diabetes mellitus // Med.Chim. – 2009. – № 4. – P. 76–79 (Ukrainian).
  5. Zdioruk M.I., Barska M.L., Brodyak I.V., Vovk O.I. Urbanovych A.M., Sybirna N.O. Influence of wortmannin on aggregation ability of neutrophylic granulocytes under type 1 diabetes mellitus / Studia Biologica.– 2009. –V.3, №2. – P. 133–140 (Ukrainian).

2010

 

  1. Bobak Y.P., Vynnytska B.O., Kurlishchuk Y.V., Sibirny A.A., Stasyk O.V. Cancer cell sensitivity to arginine deprivation in vitro is not determined by endogenous levels of arginine metabolic enzymes // Cell Biol Int.-2010.-V.34 (11).-P.1085–1089.
  2. Stadnyk V.V., Izyumovaa L.A., Rzhepetskiy Y.A., Mayor C.Y., Vlizlo V.V. The Antisense Oligonucleotides Decrease Expression of the Cellular Prion // Letters in Drug Design & Discovery.- 2010,-V.7.- P.23-26.
  3. Jóźwiak J., Rzhepetskiy Y., Sobczak M., Kocik E., Skórzewski R., Kłopocka W., Rędowicz M.J. Amebin a novel Amoeba Proteus actin-bundling protein inhibits actomyosin ATPase activity and is essential for Amoeba migration // Archives of Biochemistry and Biophysics.- 2010, (published ahead of print).

 

Tutorials and methodical editions:

  1. Chemistry of the Protein: texbook: [for university students] / [ N.О. Sybyrna, М.V. Gonchar, І.V. Brodyak, О.G. Stasyk, М.L. Barska] edited by Prof. N.О. Sybyrna. - Lviv: Ivan Franko Lviv national University. 2010 - pp.393 . Labeled by MES of Ukraine.

2011

 

  1. Vynnytska B.O., Mayevska O.M., Kurlishchuk Y.V., Bobak Y.P., Stasyk O.V. Canavanine augments proapoptotic effects of arginine deprivation in cultured human cancer cells // Anticancer Drugs. – 2011. – V.22 (2). – P. 148 – 157. (IF=2.407) (Scopus)
  2. Jozwiak J, Rzhepetskyy Y, Sobczak M, Kocik E, Skorzewski R, Klopocka W, Redowicz MJ. C-terminal fragment of amebin promotes actin filament bundling, inhibits acto-myosin ATPase activity and is essential for amoeba migration // Arch. Biochem. Biophys. – 2011. – V. 506(1). – P. 99-108. (IF=2.935) (Scopus)
  3. Nazarko V.Y., Nazarko T.Y., Farre J.C., Stasyk O.V., Warnecke D., Ulaszewski S., Cregg J.M., Sibirny A.A., Subramani S. Atg35, a micropexophagy-specific protein that regulates micropexophagic apparatus formation in Pichia pastoris // Autophagy. – 2011. – V. 7(4). – P. 375-385. (IF=7.453) (Scopus)
  4. Sybirna N., Brodyak I., Zdioruk M., Barska M. Sialic acid-containing glycoproteins are the marker molecules that determine the leukocyte functional state under diabetes mellitus // Sepsis. 2011. – V. 4(1) – P. 47-55. (Google Scholar)
  5. Стасюк Н.Є., Карпʼяк В.В., Гайда Г.З., Гайда А.В., Стасик О.В., Гончар М.В. Синтез афінних сорбентів для виділення рекомбінантної аргінази і людини із генетично модифікованих дріжджів Нansenula polymorpha //Праці НТШ, Хем. Біохем. – 2011. – Т. 28. – С.139-149. (Google Scholar)
  6. O.I. Chen, L.S. Lyniv, N.I. Igumentseva, M.L. Barska, N.O. Effect of nitric oxide donor on viability of human leukemic cells upon arginine deprivation // Studia Biologica. – 2011. – V. 5, N 2. – P. 17–28. (Google Scholar)
  7. Сибірна Н.О., Здіорук М.І., Бродяк І.В., Барська М.Л., Вовк О.І. Активація фосфатидилінозитол-3′-кіназного шляху лектиніндукованим сигналом через сіаловмісні глікопротеїни мембран лейкоцитів при цукровому діабеті 1-го типу // Укр. біохім. Журнал. – 2011. – Т. 83. - № 5. – С. 22-31. (Google Scholar)
  8. Vovk O.I., Rzhepetskyy Y.A., Pereverzeva H.G., Stasyk O.V. Expression of recombinant human argininosuccinate synthetase in Escherichia coli // Біологічні Студії / Studia Biologica. – 2011. – Том 5. - №3 - С. 19–28. (Google Scholar)
  9. Стасюк Н., Гайда Г., Гайда А., Стасик О., Карпʼяк В., Гончар М. Синтез афінних сорбентів для очищення аргінази І людини із рекомбінантних дріжджів Нansenula polymorpha // Праці НТШ, Хем. Біохем. – 2011. – Т.28. – С.139-149. (Google Scholar)
  10. Стасик О. Г., Стасик О. В. Селективна деградація пероксисом у дріжджів Hansenula polymorpha потребує стеролглюкозилтрансферазу Atg26 // Біологічні студії. – 2011. – Т.5, №2. – С. 93-104. (Google Scholar)
  11. Ю.В. Курліщук, Б.О. Винницька-Мироновська, Я.П. Бобак, О.В. Стасик (2011) Вплив метаболітів аргініну на життєздатність людських пухлинних клітин за умов дефіциту цієї амінокислоти in vitro. Біологічні студії. – 2011. - Т.5, №2. - С. 5-16. (Google Scholar)

2012

 

  1. Vynnytska-Myronovska B., Bobak Y., Garbe Y., Dittfeld C., Stasyk O., Kunz-Schughart L.A. Single amino acid arginine starvation efficiently sensitizes cancer cells to canavanine treatment and irradiation // Int. J. Cancer. – 2012. – V. 130, № 9. – P. 2164 – 2175 (IF=6.198). (Scopus)
  2. Zakalskiy AE, Zakalska OM, Rzhepetskyy YA, Potocka N, Stasyk OV, Horak D, Gonchar MV. Overexpression of (His)(6)-tagged human arginase I in Saccharomyces cerevisiae and enzyme purification using metal affinity chromatography // Protein Expr Purif. -2012.- 81(1). –P. 63-68. (IF=1.429) (Scopus)
  3. Samoylenko A., Vynnytska-Myronovska B., Byts N., Kozlova N., Basaraba O., Pasichnyk H., Palyvoda K., Bobak Ya., Barska M., Mayevska O., Rzhepetskyy Y., Shuvayeva H., Lyzogubov V., Usenko V., Savran V., Volodko N., Buchman V.L., Kietzmann T., Drobot L. Increased levels of the HER1 adaptor protein Rukl/CIN85 contribute to breast cancer malignancy // Carcinogenesis. - 2012.- Vol. 33, №10.-P. 1976-1984 (IF=5.635) (Scopus)
  4. Сибірна Н.О., Бродяк І.В., Барська М.Л., Вовк О.І. Участь ензиму фосфатидилінозитол-3ʼ-кінази у процесах сприйняття і передачі сигналів через галактозилумісні глікопротеїнові рецептори сегментоядерних лейкоцитів при цукровому діабеті 1 типу // Фізіологічний журнал. – 2012. - T. 58, №6. - С. 9-22. (Google Scholar)
  5. O. Chen, M. Barska, N. Sybirna, O. Stasyk. Development and evaluation of HPLC method for arginine assay in biological samples // Вісник Львівського університету. Серія біологічна. – 2012. – Том 60. –С. 73–82. (Google Scholar)

2013

 

  1. Krasovska O.S., Stasyk O.V., Sibirny A.A. Stable overproducer of hepatitis B surface antigen in the methylotrophic yeast Hansenula polymorpha due to multiple integration of heterologous auxotrophic selective markers and defect in peroxisome biogenesis // Appl. Microbiol. Biotechnol. – 2013. – Vol. 97, No. 23. – P. 9969-9979 (ІF=3.811) (Scopus)
  2. Vynnytska-Myronovska B., Kurlishchuk Y., Bobak Y., Dittfeld C., Kunz-Schughart L.A., Stasyk O. Three–dimensional environment renders cancer cells profoundly less susceptible to a single amino acid starvation // Amino Acids. – 2013. – V. 45, № 5. – P. 1221-1230 (IF=3.653) (Scopus)
  3. Chen O., Kavalets B., Barska M., Lyniv L., Vovk O., Sybirna N. Stasyk O. Effect of combinational arginase and canavanine treatment on normal human peripheral blood lymphocytes in vitro // Curr. Issues Pharm. Med. Sci. – 2013 - Vol. 26, No. 4, Pages 385–389. (Scopus)
  4. Sybirna N.O., Brodyak I.V., Barska M.L., Vovk O.I. Participation of Phosphatidylinositol-3ʼ-kinase in Perception and Signal Transduction through Galactosyl-Containing Glycoprotein Receptors of Segmented Leukocytes under Type 1 Diabetes Mellitus // International Journal of Physiology and Pathophysiology. – 2013– V.4, №3. – P. 213-230. (IF=0.150) (Google Scholar)

2014

 

  1. Petryk N., Zhou Y.F., Sybirna K., Mucchielli M.H., Guiard B., Bao W.G., Stasyk O.V., Stasyk O.G., Krasovska O.S., Budin K., Reymond N., Imbeaud S., Coudouel S., Delacroix H., Sibirny A., Bolotin-Fukuhara M. Functional study of the Hap4-like genes suggests that the key regulators of carbon metabolism HAP4 and oxidative stress response YAP1 in yeast diverged from a common ancestor. PLoS One. 2014 Dec 5;9(12):e112263. doi: 10.1371/journal.pone.0112263. eCollection 2014. (IF=3.234) (Scopus)
  2. Shuvayeva Galyna, Bobak Yaroslav, Igumentseva Natalia, Titone Rossella, Morani Federica, Stasyk Oleh, Isidoro Ciro. Single Amino Acid Arginine Deprivation Triggers Prosurvival Autophagic Response in Ovarian Carcinoma SKOV3 // BioMed Research International. Volume 2014 , Article ID 505041, 10 pages, (IF=1.579) (Scopus)
  3. Mathias Stiller, Martyna Molak, Stefan Prost, Gernot Rabeder, Gennady Baryshnikov, Wilfried Rosendahl, Susanne Münzel, Hervé Bocherens, Aurora Grandal-dʼAnglade, Brigitte Hilpert, Mietje Germonpré, Oleh Stasyk, Ron Pinhasi, Andrea Tintori, Nadin Rohland, Elmira Mohandesan, Simon Y.W. Ho, Michael Hofreiter, Michael Knapp Mitochondrial DNA diversity and evolution of the Pleistocene cave bear complex // Quaternary International. – 2014. – 339–340:224-231 (IF=2.062) (Scopus)
  4. Vynnytska-Myronovska B.O., Bobak Y.P., Pasichnyk G.V., Igumentseva N.I., Samoylenko A.A., Drobot L.B.. Multiple molecular forms of adaptor protein Ruk/CIN85 specifically associate with different subcellular compartments in human breast adenocarcinoma MCF-7 cells. Ukr Biochem J. 2014 Sep-Oct;86(5):102-10. (Google Scholar)
  5. Denega I.O., Klymyshyn N.I., Sybirna N.O., Stasyk О.V., Stasyk О.G.. Modeling of molecular processes underlying Parkinsonʼs disease in cells of methylotrophic yeast Hansenula polymorpha // Біологічні студії/Studia Biologica. – 2014. – Т. 8, № 12. – C. 5–16. (Google Scholar)

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