Department of Molecular Oncogenetics

The Department was established on the basis of the Department of Biochemical Genetics (Prof. A. P. Solomko).

Head

Volodymyr I. Kashuba

Professor, Dr. Sci. (Mol. Biol.)
Phone: (380-44) 526-07-09;
Fax: (380-44) 526-07-59;
E-mail: v.i.kashuba@imbg.org.ua

Education and Degrees:

19771983 Graduate Student, Faculty of Chemistry, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine, M.Sc. (biochemistry)

1991 Ph.D. (molecular biology)

2009 Dr.Sci. (molecular biology)

Professional Employment:

19831989 Engineer, Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics (IMBG), NASU, Kyiv, Ukraine

19891991 Junior Research Scientist, IMBG NASU, Kyiv, Ukraine

19912009 Research Scientist, IMBG NASU, Kyiv, Ukraine

20092011 Senior Research Scientist, IMBG NASU, Kyiv, Ukraine

since 2011 Head of the Department of Molecular Oncogenetics, IMBG NASU, Kyiv, Ukraine

Membership:

since 1995 Member of European Association for Cancer Research (EACR)

since 2010 Member of Ukrainian Society of Geneticists and Breeders

Research Area:

Identification of genetic and epigenetic changes in malignant epithelial tumors

urrent Research Activities and Recent Achievements:

Identification of molecular-genetic markers for early detection and prognosis of epithelial tumors.

We analyze different types of epithelial tumors (breast, kidney, cervical, colon, ovarian and lung) with Not-I microarray technology. We have found loc/genes with changes in high percents of samples. Further cluster analysis permits to select genes candidates for discrimination different cancer stages. Not-I microarray technology allows the development of marker panels for the detection of differences between types of cancer and discrimination of stages, for early detection, presence or absence of metastases and the tumor aggressiveness.

On the basis of the case study the panel of 19 markers was created for detection of lung carcinoma, differentiation between adenocarcinoma and squamous lung carcinoma with or without methastases. For ovary carcinoma the panels of 11 markers were created for early detection, discrimination of benign tumors and cancer, and discrimination of I + II stages and III + IV stages. We considered a new approach to search for epithelial cancer epigenetic markers. The results are perspective for use in practical medicine.

Fig. 1. Hybridization pattern of DNA from NSCLC samples (SCC and ADC) on NotI-microarrays. Horizontally 40 NSCLC samples. Vertically 44 NotI sites arranged by methylation/deletion frequency (from 58 % to 15 %).
The baculovirus expression system for obtaining recombinant proteins.

We investigate the potential of the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) as a safe alternative vehicle in different strategies of cancer therapy. On mouse models we examine baculoviruses ability for targeting cancer cells or transducing hypothetical vector cells that in turn target tumors. For this we assessed the efficiency of different constructed recombinant baculovirus vectors (with the GFP reporter gene and a number of therapeutic cytokine genes under the control of strong mammalian promoters) in transduction of different mouse normal and tumor cell lines. It was shown that coculture of melanoma cells with fetal fibroblasts, transduced with the recombinant baculovirus vector expressing mouse therapeutic β-interferon, leads to inhibition of malignant cell growth (Fig.2) and coinjection of melanoma cells and transduced fibroblasts causes tumor growth inhibition and increase in life-span of experimental animal.

Fig. 2. The growth inhibition of tumor mouse melanoma cells (MM4) during coinjection with murine fetal fibroblasts (C57Fb), transduced with the recombinant baculovirus vector expressing mouse β-interferon (Ifnβ).

We also use baculovirus expression system for production and study of a number of protein tumor-suppressors.

National Grants:

Projects of National Academy of Sciences of Ukraine:

  • 20102014 N 22/12 Project: Functional bionanomaterials for medical diagnostics of oncological diseases (scientific supervisor Kashuba V. .)
  • 20102014 N 41/12 Project: Identification of moleculargenetic markers for diagnostics of the epithelial malignant tumors (scientific supervisor KashubaV. .)
  • 20102014 N 33/12 Project: Recombinant baculovirus vectors efficacy research and construction for gene and vaccine therapy (scientific supervisor Strokovskaya L. I.)

Projects of State Fund for Fundamental Researches:

  • 20112012 N F/40 Project: Molecular mechanisms of D-glucorunil C5-epimerase inactivation in cancerogenesis (scientific supervisor Kashuba V. .)
  • 2006 N 18/012 Project: Identification and characterization of genes, which are specific for renal and ovarian cancer (scientific supervisor Kashuba V. .)

Projects of State Agency on Science, Innovations and Informatization of Ukraine:

  • 2012 N SP/487 Project: Creation and introduction to exploitation of the laboratory module for a microarrays design and application (scientific supervisor Kashuba V. .)

International Grants:

  • 20042006 NTAS (The International Association for the Promotion of Co-operation with Scientists from the New Independent States of the Former Soviet Union) N 03-51- 4983 Project: Not I microarrays for identification of new cancer-causing genes

Collaboration:

with Ukrainian organizations:

  • R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU (Kyiv)
  • V. E. Lashkaryov Institute of Semiconductor Physics, NASU (Kyiv)

Selected publications:

  1. A. Suhovskih, V. Kashuba, G. Klein, E. Grigorieva. Prostate cancer cells specifically reorganize epithelial cells- fibroblast communication through proteoglycan and junction pathways. Cell Adhesion & Migration. 2016:1-15.
  2. I.M. Kikhno, V.E. Makarenko, V.I. Kashuba. Functional complementation of conserved non protein-coding element ( CNE) originated from Malacosoma neustria nucleopolyhedrovirus. Biopolymers and Cell. 2016, 32(3):131-139.
  3. L.G. Buchynska, N.P. Iurchenko, N.P. Verko, K.A. Nekrasov, V.I. Kashuba. FOXP3 gene promoter methylation in endometrial cancer cells. Experimental Oncology. 2015, 37(4):246-249.
  4. L.G. Buchynska, O. V. Brieieva, K.A. Nekrasov, S.V. Nespryadko. The Study of Mismatch Repair in Endometrial Cancer Patients with A Family History of Cancer. Experimental Oncology. 2015, 37(4):272-276.
  5. Rudenko E, Lapska Y, Gerashchenko G, Stakhovsky E, Vikarchuk M, Kashuba V. Heterozygous deletions are main cause of expression alterations of PPM1M and PRICLE2 genes in human clear cell renal cell carcinomas. Biopolymers and Cell. 2015;31(1):29-33.
  6. Rudenko E, Kondratov O, Gerashchenko G... Kashuba V. Aberrant expression of selenium-containing glutathione peroxidases in clear cell renal cell carcinomas. Exp Oncol. 2015;37(2):105-110.
  7. Loginov V, Dmitriev A, Senchenko V... Kashuba V. Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers. PLoS One. 2015;10(5):1-21.
  8. Alexeyenko A, Alkasalias T, Pavlova T...Kashuba V, at all. Confrontation of fibroblasts with cancer cells in vitro: gene network analysis of transcriptome changes and differential capacity to inhibit tumor growth. J Exp Clin Cancer Res. 2015;34(1).62:2-17.
  9. Lykhova A, Kudryavets Y, Strokovska L...at all. Supression of proliferation, tumorigenicity and metastasis of lung cancer cells after their transduction by interferon-beta gene in baculovirus vector. Cytokine. 2015;71:318-326.
  10. Rosenberg E, Prudnikova T, Zabarovsky E., et al. D-glucuronyl C5-epimerase cell type specifically affects angiogenesis pathway in different prostate cancer cells. Tumor Biology. 2014; 35(4):3237-3245.
  11. Kondratov AG, Nekrasov KA, Lototska LV, et al. Comparative analysis of epigenetic markers in plasma and tissue of patients with colorectal cancer. Biopolymers and Cell. 2014;30(1):129-134.
  12. Dmitriev A, Rudenko E, Kudryavtseva A, et al. Epigenetic Alterations of Chromosome 3 Revealed by NotI-Microarrays in Clear Cell Renal Cell Carcinoma. BioMed Research International Volume 2014 (2014), Article ID 735292, 9 pages. http://dx.doi.org/10.1155/2014/735292
  13. Kikhno I. Identification of Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis. PLOS ONE. 2014;9(4):1-15.
  14. Rosenberg E, Prudnikova T, Gerashchenko A, et al. Search for genes potential markers of aggressiveness and metastasis for human prostate cancer. Biopolymers and Cell. 2013;29(6):499-505.
  15. Gordiyuk V. V., Kondratov A. G., Gerashchenko G. V., Kashuba V. I. Novel epigenetic markers of early epithelial tumor growth and prognosis Biopolym. Cell. 2013; 29(3):215-220 doi:10.7124/bc.00081B
  16. Rudenko EE, Gerashchenko GV, Lapska YY, et al. Genetic and epigenetic changes of GPX1and GPX3 in human clear- cell renal carcinoma. Biopolym. Cell. 2013; 29(5):395401 doi:10.7124/bc.00082F
  17. Law EW, Cheung AK, Kashuba VI, et al. Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma. Oncogene. 2012; 31(6): 72838 doi:10.1038/onc.2011.272
  18. Kashuba V, Dmitriev AA, Krasnov GS, et al. NotI Microarrays: Novel Epigenetic Markers for Early Detection and Prognosis of High Grade Serous Ovarian Cancer. Int J Mol Sci. 2012; 13(10): 1335277 doi:10.3390/ijms131013352
  19. Kondratov AG, Kvasha SM, Stoliar LA, et al. Alterations of the WNT7A gene in clear cell renal cell carcinomas. PLoS One. 2012; 7(10):e47012 doi:10.1371/journal.pone.0047012
  20. Kondratov AG, Stoliar LA, Kvasha SM, et al. Methylation pattern of the putative tumor-suppressor gene LRRC3B promoter in clear cell renal cell carcinomas. Mol Med Report. 2012;5(2):50912 doi:10.3892/mmr.2011.681
  21. Haraldson K, Kashuba VI, Dmitriev AA, et al. LRRC3B gene is frequently epigenetically inactivated in several epithelial malignancies and inhibits cell growth and replication. Biochimie. 2012; 94(5):11517 doi:10.1016/j.biochi.2012.01.019
  22. Prudnikova TY, Mostovich LA, Kashuba VI, Ernberg I, Zabarovsky ER, Grigorieva EV. miRNA-218 contributes to the regulation of D-glucuronyl C5-epimerase expression in normal and tumor breast tissues. Epigenetics. 2012; 7(10):110914 doi:10.4161/epi.22103
  23. Dmitriev AA, Kashuba VI, Haraldson K, et al. Genetic and epigenetic analysis of non-small cell lung cancer with NotImicroarrays. Epigenetics. 2012; 7(5):50213 doi:10.4161/epi.19801
  24. Solomko AP, Zaharuk OA, Chaschina LI, Strokovskaya LI. Baculovirus vectors in experimental gene- and vaccine therapy. Biopolym. Cell. 2011; 27(3):16780 doi:10.7124/bc.0000B7
  25. Kashuba VI, Li J, Wang F, Senchenko VN, et al. RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies. Proc Natl Acad Sci USA. 2004; 101(14):490611 doi:10.1073/pnas.0401238101