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.