Department of Functional Genomics

Scientific research is conducted in the areas:

Regulation of functional diversity of adaptor/scaffold proteins

Identification and analysis of tumor suppressor genes implicated in the development of major epithelial cancers

Regulation of gene expression at the level of alternative splicing (under normal and pathological conditions)

Molecular retrovirology

Recent achievements:

• The role of alternative splicing in the modulating of functions of Down syndrome related adaptor protein Intersectin 1 (ITSN1) implicated in endocytosis, apoptosis, mitogenic signaling pathways and cytoskeleton rearrangements is studied. Fifteen novel splicing events affecting ITSN1 transcripts were identified. It was shown how alternative splicing affecting the SH3A domain regulates the binding properties of ITSN1 and creates two pools of ITSN1 isoforms with different properties in neurons.
• Our studies are focused on identification of novel ITSN interacting partners and their functional significance, as well as determination of functional differences between paralogous genes of ITSN family.
• We study the methylation status, genetic changes and expression of potential cancer-causing genes from human chromosome 3 in major epithelial tumors identified by NotI-microarrays. The possible application of these genes as parts of multiple genetic markers tools for clinically useful predictions is under analysis.
• Identification, localization and expression of endogenous retroviruses in a host genome are elucidated in view of their potential role in neoplasm formation.

Selected publications:

1. Tsyba, L., Gryaznova, T., Dergai, O., Dergai, M., Skrypkina, I., Kropyvko, S., Boldyryev, O., Nikolaienko, O., Novokhatska, O. and Rynditch, A. (2008) Alternative splicing affecting the SH3A domain controls the binding properties of intersectin 1 in neurons. Biochem Biophys Res Commun, 372, 929-934.
2. Borisenko, L., Stepanets, V. and Rynditch, A.V. (2008) Molecular characterization of full-length MLV-related endogenous retrovirus ChiRV1 from the chicken, Gallus gallus. Virology, 376, 199-204.
3. Kvasha, S., Gordiyuk, V., Kondratov, A., Ugryn, D., Zgonnyk, Y.M., Rynditch, A.V. and Vozianov, A.F. (2008) Hypermethylation of the 5'CpG island of the FHIT gene in clear cell renal carcinomas. Cancer Lett., 265, 250- 257.
4. Kashuba, V.I, Skripkina, I.Ia, Saraev, D.V, Gordiiuk, V.V, Vinnitskaia, A.B, Tsyba, L.A, Pogrebnoi, P.V, Blinov, V.M, Zabarovskii, E.R, Rynditch, AV. (2006) Identification of changes in gene loci potentially associated with cervical cancer using NotI microarrays. Ukr Biokhim Zh., 78, 113-120.
5. Razin, S., Rynditch, A., Borunova, V., Ioudinkova, E., Smalko, V. and Scherrer, K. (2004) The 33 kb transcript of the Chicken ?-globin gene domain is part of the nuclear matrix. J. of Cell. Biochemistry, 92, 445-457.
6. Tsyba, L.O., Skrypkina, I.Ya., Rynditch, A.V., Nikolaienko, O., Ferenez, G., Fortna, A. and Gardiner K. (2004) Alternative splicing of mammalian Intersectin 1: domain associations and tissue specificities. Genomics, 84, 106-113.
7. Tsyba, L., Rynditch, A., Boeri, E., Jabbari, K. and Bernardi, G. (2004) Distribution of HIV-1 in the genomes of AIDS patients. Cell. Mol. Life Sci., 61, 721-726.