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Research

Prof Nikolai Zhelev

  • Role: Director Of CMCBR
  • Division: SSET - SIMBIOS
  • Department: School of Science Engineering & Tech.
  • Office location: Kydd Building, Simbios
  • Telephone number: +44 (0)1382 308536
  • Email: n.zhelev@abertay.ac.uk

Research

The research in my laboratory aims to understand the regulation of the signal transduction pathways related to tumorigenesis, through the development of methods that can provide quantitative information about the complex interactions of such pathways in real time in a single cell. We have developed the first live-cell biosensor for monitoring activity on cancer targets such as cyclin-dependent kinases in tumours. In addition, we are working with biopharmaceutical and biotech companies on the development of novel drugs against cancer and cardiac hypertrophy and novel nanobiotechnology tools to study molecular interactions.

We are collaborating and publishing joint papers with a number of research institutions including: Harvard Medical School, University of Edinburgh,  A* STAR Singapore, University of Namur, University of Liege, Medical University Sofia, Medical University Plovdiv, Technical University Varna, Sofia University,  Trakia University,  University of Dundee, The Roslin Institute and Royal School of Veterinary Sudies, St James’s University Hospital Leeds, Howard Hughes Medical Institute, Novartis Institutes for Biomedical Research and Dana-Farber Cancer Institute. We are also working with industrial partners namely:  Cyclacel Pharmaceuticals Inc., Scientific Technological Service (STS) Ltd. and  Norton Scientific Inc.

Teaching

Lectures:           

Module title: Industrial/Biomedical Biotechnology (BI1103) – for MSc

Module title: Industrial/Biomedical Biotechnology (BI1104) – for BSc

Module title: Professional Studies (BI0704A)

Module title: Adult Nursing (HE0808A)

Labs:

Module title: Techniques and Skills (BI0703A)

Tutorials:

Module title: Principles of biology (BI0701A)

Knowledge Exchange

Publications

Khalil HS, Tummala H, Chakarov S, Zhelev N. Lane DP. Targeting ATM pathway for therapeutic intervention in cancer. BioDiscovery. 2012 vol 1  3

Tummala H, Khalil HS, Mitev V, Zhelev N, A quantitative integrated systems biology approach for modeling cell cycle pathways in normal and tumor cells. Cancer Res. 2012 vol 72(8) p 4913

 Khalil, HS, Tummala H, Zhelev N. Differences in the DDR enzymes activation kinetics between normal and cancer cells could be utilized to achieve targeted cellular sensitivity towards genotoxic agents. Cancer Res. 2012 vol 72(8) p 3103

 Khalil, HS, Tummala H, Zhelev N. Phosphorylated ATM at S-1981 (pATM) undergoes COPI mediated Golgi export upon DNA damage. FEBS J 2012 vol 279(S1) p 146

 Tummala H, Khalil HS, DAscanio I, Wehner D, Lester DH, Babraj J, Zhelev N. Human 825C>T polymorphism in GNB3 gene promotes enhanced cell migration by inducing cytosolic calcium influx and hyper phosphorylation of ERK regulated mTOR pathway. FEBS J 2012 vol 279(S1) p 141

Khalil HS, Tummala H, Hupp TR, Zhelev N. Pharmacological inhibition of ATM by KU55933 stimulates ATM transcription  Exp. Biol. Med.2012 vol  237(6) p 622 

Mustaffa M, Zhelev N. You cannot always win: molecular bases of the resistance of picornavirusesto WIN compounds. Biotech & Biotech Eq. 2012 vol 26(2) p 2826

Khalil HS, Petkova R, Zhelev N. Differential genetic advantages in youth and in aging, or how to die healthy.  Biotech & Biotech Eq. 2012 vol 26(1) p 2703

Vlaykova T, Gulubova M, Yovchev Y, Dimov D, Vlaykova D, Chilingirov P, Zhelev N. Glutathione-S-transferases in development, progression and therapy of colorectal cancer 2011 In Colorectal Cancer / Book 1 Intech Open Access Publisher, Rijeka p 81

Petkova R, Tummala H, Zhelev N. Nothing in excess – lessons learned from the expression of high-mobility group proteins type A in non-cancer and cancer cells. Biotech & Biotech Eq. 2011  vol 25(4) p 2572

Zhelev N. The “golden age” of biotechnology in Europe. Biotech & Biotech Eq. 2011  vol 25(4) p 2688

Tummala H; Fleming S; Hocking PM; Ali M; Inglehearn CF; Zhelev N; Lester DH. Mutant GNB3 gene mediates aberrant signalling events leading to renal and visual anomalies in rge chickens.  PLoS . 2011 vol 6 (8) p 21156

Tummala H, Khalil HS, Nikolova E, Mitev V, Zhelev N. Cell-based nanosensors for systems biology research and drug development. Curr Opin Biotech 2011 vol 22(1) p 25

Tummala H, Khalil HS, Zhelev N. Repair, abort, ignore? Strategies for dealing with UV damage. Biotech & Biotech Eq. 2011  vol 25(3) p 2443

Clyde RG, Tummala H, Khalil HS, Goszcz K, Lucka I, Tupone MG, Zwirek M, Cavicchi L, Vallatur J, Stoyanova V, Mitev V, Zhelev N (2011). A novel quantitative systems biology approach to cancer research and treatment. Curr Opin Biotech 2011 vol 22(1) p 58

Khalil HS, Tummala H, Omoboye AO, Zhelev N. Novel insights of ATM regulation and its potential as a target for therapeutic intervention in cancer  Curr Opin Biotech 2011 vol 22(1) p 115

Idowu MA,  Goltsov A, Khalil HS, Tummala H, Zhelev N, Bown J. Cancer research and personalized medicine: a new approach to modeling time-series data using analytical methods and Half systems. Curr Opin Biotech  2011 vol 22(1) p 59

White R, Zhelev N, Bradley D. Issues of Innovation, Design and Development in Relation to the Implementation of Light Scattering Instrumentation. 2011 In Mechatronics and manufacturing engineering (J.P. Davim ed.) Woodhead Publishing, Cambridge, p 1

Stoyanova V, Zhelev N, Ghenev E, Bosheva M.Assessment of left ventricular structure and function in rats subjected to pressure-overload hypertrophy in time. Kardiol Pol. 2009 ;vol 67(1) p 2 

Zhelev N. Thymidine kinase. (2008). Patent PCT publication, International Publication Number WO/2009/06325 

Stoyanova V, Zhelev N. Alterations in protein P53 expression during the development of pressure overload-induced left  ventricular hypertrophy in rats: .Biotechnol. & Biotechnol. Eq 2008 vol. 22 (4) p 977

Atanasova G, Isaeva A, Zhelev N, Poumay Y, V Mitev. Effect of the CDK-inhibitor CYC202 on p38MAPK, ERK ½ , c-Myc activities and proliferation of papillomavirus type 16 E6E7-transformed keratinocytes. Oncology Reports 2007 vol. 18, (4)  p 999

Nikolova E, Mitev V, Zhelev N, Deroanne CF, Poumay Y. The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc. Biochem Biophys Res Commun. 2007 vol 359: p 834

Neychev VK, Nikolova E, Zhelev N, Mitev VI. Saponins from Tribulus terrestris L are less toxic for normal human fibroblasts than for many cancer lines: influence on apoptosis and proliferation. Experimental Biology and Medicine .2007 vol  232 (1) p 126

Fischer P.M., Zhelev N., Shudong W. Transport Vectors Patent Number US 07173931,  2006

Miteva L, Zhelev N, Mitev V. Molecular targets for hyperproliferating skin diseases. Allergy Hypersensitivity Asthma  2006 vol 4 p  

Clyde R.G,, Bown J.L, Hupp T.R, Zhelev N, Crawford J.W. The role of modeling in identifying drug targets for diseases of the cell cycle. J. R. Soc. Interface 2006 vol. 3(10) p 617

Fischer P.M., Zhelev N. Transport Vectors Patent Number US 07101967  2006.

Stoyanova V, Dobreva B, Ghenev E, Zhelev N. In vivo assessment of left ventricular hypertrophy in rats: necropsy validation. Biotechnol. & Biotechnol. Eq 2006 vol. 20 (2) p 12 

Wang S, Zhelev N.Z, Duff S, Fischer P.M. Synthesis and biological activity of conjugates between paclitaxel and the cell delivery vector penetratin. Bioorg Med Chem Lett. 2006 vol. 16(10) p 2628

Fischer P.M., Wang S., Zhelev N. Carrier based drug delivery system. Patent Number US 06992169  2006.

Zhelev N., Barudov S. Laser light scattering applications in biotechnology. Biotechnol. & Biotechnol. Eq. 2005 vol. 19 (3) p 3

Stoyanova V.K, Zhelev N.Z., Yanev I.B, Ghenev E.D, Nachev C.K Time course and progression of pressure overload-induced cardiac hypertrophy in rats. Folia Med 2005 vol. 47(2) p 52

Atanasova G, Jans R, Zhelev N, Mitev V, Poumay Y. Effects of the cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) on the physiology of cultured human keratinocytes. Biochem Pharmacol. 2005 vol. 70(6) p 824

Zhelev N, Neichev V. The significance of the type quality and form of the carbohydrate intake for the optimum re-synthesis of the muscular glycogen during the first restoration phase.  Medicine and Sport  2005 vol. 2 p 32

Zhang GJ., Safran M, Wei W, Sorensen E, Lassota P, Zhelev N, Neuberg D.S, Shapiro G, Kaelin W.G Jr. Bioluminescent imaging of Cdk2 inhibition in vivo. Nature Medicine. 2004  vol. 10(6) p 643

Neichev V.K, Nikolova E.M, Zhelev N, Mitev V.I. Investigation of the influence of Tribulus terrestris extract on proliferation of normal human skin fibroblasts.  Oncologos 2004 vol. 1 p 89

Atanasova G, Jans R, Zhelev N, Mitev V, Poumay Y.G.. Cell cycle arrest by CDK inhibitor CYC202 (R-roscovitine) in normal human keratinocytes is followed by induction of p38 MAPK phosphorylation and subsequent involucrin expression. on the physiology of cultured human keratinocytes. Journal of Investigative Dermatology. 2004 vol. 122(3) p 95

Isaeva A.P. Petrov S, Zhelev N. Effect  of polyamines on the proliferation of normal and cancer cells. Isaeva A.P, Petrov S, Zhelev N. Effect of polyamines on proliferation of normal and tumour  cells Oncologos 2004 vol. 1 p 83

Sarek J, Klinot J, Dzubak P, Klinotova E, Noskova V, Krecek V, Korinkova G, Thomson J.O, Janostakova A, Wang S, Parsons S, Fischer P.M, Zhelev N.Z, Hajduch M. New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure-activity relationships J Med Chem. 2003 vol. 46(25) p 5402

Fischer P.M., Wang S., Zhelev N. Carrier based drug delivery system. Patent Number US 6472507  2002 

McClue S.J, Blake D, Clarke R, Cowan A, Cummings L, Fischer P.M, MacKenzie M, Melville J, Stewart K, Wang S, Zhelev N, Zheleva D, Lane DP. In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine). Int J Cancer. 2002 vol. 102(5) p 463

Zheleva D.I., McInnes C., Gavine A.L.., Zhelev N.Z., Fischer P.M., Lane D.P. Highly potent p21(WAF1)-derived peptide inhibitors of CDK-mediated pRb phosphorylation: delineation and structural insight into their interactions with cyclin A. J Pept Res. 2002 vol. 60(5) p 257

McClue S., Fischer P.M, Blake D, Clarke R, Duff S., Krauss E., Cummings L, Stewart K, Melville J, Wang S, Zhelev N, Zheleva D. Studies on the mechanism of action of CYC202 (R-roscovitine). Proc.  AACR. 2002 vol. 43 p 666

Wang S., Blake D., Clarke R., Duff S., McClue S., McInnes C., Melville J., Stewart K., Taylor P., Westwood R., Wood G., Wu S.., Zhelev N.Z.; Zheleva D. I.; Walkinshaw M., Lane D. P.; Fischer P. M. 4-Heteroaryl-2-phenylamino-pyrimidines, a new class of CDK2 inhibitors: Discovery, optimization, and antiproliferative activity in vitro and in vivo. Proc.  AACR. 2002 vol. 43 p 848

Fischer P.M., Zheleva D.I., McInnes C., Gavine A.L., Zhelev N.Z., Lane D.P. Peptide inhibitors of cyclin-dependent kinases derived from p21(WAF1): delineation and structural insight into their interactions with cyclin A. Clin. Cancer Res. 2001 vol 7 (11) p 3821

Whittaker, S., Walton, M., Kelland, L., Garrett, M., Zhelev, N. and  Workman, P. Rb Phorphorylation as a pharmacodynamic marker of Roscovitine (CYC202) activity in vitro and in vivo. Proc.  AACR  2001  vol 42, p 926.

Kovarova H., Hajduch M., Korinkova G., Halada P., Krupickova S., Gouldsworthy A. Zhelev N.Z and Strnad M. Proteomics approach in classifying the biochemical basis of the anti-cancer activity of a new olomoucine-derived synthetic cyclin dependent kinase inhibitor, bohemine.  Electrophoresis 2000  vol. 21, p 3757.

Zheleva D. I., Zhelev N. Z., Fischer P. M., Duff S.V.,  Warbrick E,  Blake D. G., and Lane, D. P A quantitative study of the in vitro binding of the C-terminal domain of p21 to PCNA - affinity, stoichiometry, and thermodynamics. Biochemistry  2000 vol.39(25), p 7388.

Zheleva D. I., Fischer P.M., Zhelev N. Z., Melville J. E., Gavine A-L., and Lane D. P. Design of cell-permeable peptides inhibitors of cyclin D1/ CDK4 complex. M. Nature Biotech.. Sh.R. 2000   vol. 11, p 25

Zhelev N. Z., Zheleva D. I., Fischer P.M., Duff S.V., and Lane D. P. Growth inhibitory effect of peptides derived from the C-terminal domain of P21waf is mediated by cyclin D1/CDK4 inhibition: PCNA binding is not essential. M. Nature Biotech. Sh.R. 2000)  vol. 11, p 22

Zheleva D. I., Zhelev N. Z., Fischer P.M., Duff S.V., Chan W., Gouldsworthy A. M., and Lane D. P. Affinity capture method for identification of peptide inhibitors of cyclin dependent kinases. M. Nature Biotech.. Sh.R. 2000  vol. 11, p 83

Fischer P. M., Zhelev N. Z., Wang S., Melville, J. E., Fåhraeus R., and Lane, D. P. Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector Penetratin. J. Peptide Res. 2000  vol. 55 (2), p 163 .

Fischer P. M., Zhelev N. Z., Fåhraeus R., Ball K. L., Warbrick E., and Lane, D. P.  Intracellular delivery of cell-cycle inhibitor peptides by Penetratin, a 16-residue peptide from the Antennapedia homeoprotein. In Peptides 1998, (Bajusz S., and Hudecz F., Eds.), p 700.

Zhelev N. Zh., Barratt M. J. and Mahadevan L. C. Use of reversed-phase high-performance liquid chromatography on polystyrene-divinylbenzene columns for the rapid separation and purification of acid-soluble nuclear proteins. J. Chromatogr. 1997. vol. 763, p 65 

Zhelev N.Zh., Buckle R., Snyder D. and Marsh P. Studying of protein-DNA binding by dynamic light scattering.. Cell Mol. Biol. L. 1996 vol. 1(2), p 199.

Zatsepina O. V., Zhelev N. Zh. and Jordan E. G. Immunolocalization of nucleolar protein B23 in mitotic centrosomes. Mol. Biol. 1995  vol. 29(6), p1359

Barratt M. J., Hazzalin C. A., Zhelev N. Zh. and Mahadevan L. C.  A mitogen- and anisomycin- stimulated kinase phosphorylates HMG14 in its basic amino-terminal domain in vivo and on isolated mononucleosomes. EMBO J. 1994 vol. 13(19), p 4524.

Kardalinou E., Zhelev N. Zh., Hazzalin C. A. and Mahadevan L. C. Anisomycin and rapamycin define an area upstream of p70/85 S6K containing a bifurcation to histone H3-HMG-like protein phosphorylation and c-fos, c-jun induction. Mol. Cell. Biol. 1994 vol. 14(2), p 1066 

Zhelev N. Zh., Kardalinou, E., Hazzalin C. A., Cano E., Barratt M. J. and Mahadevan L.C. Signalling to chromatin and the superinduction of proto-oncogenes. Biochem. Soc. Trans. 1993   vol. 21, p 907.

Kicheva, M. I.; Zhelev, N. Zh.; Popova, L. P. Effect of water stress on protein synthesis in two wheat cultivars differing in drought tolerance. C. R. Acad. Sci. Bulg. 1993 vol. 46(3), p 95.

Miteva T. S., Zhelev N. Zh. and Popova L. P. Effect of salinity on the synthesis of ribulose-1,5,-bisphosphate carboxylase/oxygenase in barley leaves. J Plant Physiol. 1992 vol. 140(1), p 46.

Zhelev N. Zh., Bachvarova N. N. and Chelibonova-Lorer H. O-Glycosylation of total cellular proteins during the cell cycle. C. R. Acad. Sci. Bulg. 1992 vol. 45(1), p 73.

Todorov, I.T., Zhelev, N.Zh., Philipova, R.N. and Hadjiolov, A.A. (1990). Synthesis and phosphorylation of the 125 kDa nuclear matrix protein mitotin during the cell cycle. In Nuclear structure and function (I.B.Zbarsky and J.R.Harris, eds), Plenum London, p 323.

Zhelev, N.Zh., Todorov, I.T. Philipova, R.N., and Hadjiolov, A.A. Phosphorylation-related accumulation of the 125K nuclear matrix protein mitotin in human mitotic cells. J. Cell Sci. 1990 vol. 95, p 59 

Pironcheva, G.L., Semionov, E.P., and Zhelev, N.Zh. Heat shock reaction in cells. Adv. Molec. Biol. 1989 vol. 8, p 73.

Zhelev, N.Zh., Philipova, R.N., Todorov, I.T. and Hadjiolov, A.A. Differential stability of the 125 kDa nuclear matrix protein mitotin in the cell cycle. C. R. Acad. Sci. Bulg. 1989  vol. 42(11), p 103.

Pironcheva, G., Zhelev, N.Zh., and Russev, G. Isolation of U5 snRNP particles. Cytobios 1988 vol. 56, p39.

Todorov, I.T., Philipova, R.N., Zhelev, N.Zh. and Hadjiolov, A.A. Changes in a nuclear matrix antigen during the cell cycle: interphase and mitotic cells. Biol. Cell 1988 vol. 62, p 105.

Philipova, R. N., Zhelev, N. Zh., Todorov, I. T. and Hadjiolov, A. A.      Monoclonal antibody against a nuclear matrix antigen in proliferating cell. Biol. Cell 1987 vol.60, p 1.

Todorov, I. T., Philipova, R. N., Zhelev, N. Zh. and Hadjiolov, A. A.      Monoclonal antibody to a nuclear antigen of human B-lymphoblastoid cells. Cell Biol. Int. Rep. 1987 vol.11(3), p 181

 

Funding

My group has received research funding from the Scottish Enterprise, Royal Society of Edinburgh, Socrates Erasmus, Carnegie Trust, the UK Government and Northwood Trust.

Outreach

Esteem

Honours

Fellow of the Institute of Biology (UK)

Full Member of the Bulgarian National Academy of Medicine

Doctor Honoris Causa (Medical University Plovdiv)

Professional Activities

2012 - present   Managing Editor, BioDiscovery

2011 - present   Visiting Professor, Fujian University of Traditional Chinese Medicine

2005 - present   Editor, Medicine and Sport

2005 - present   Editorial Board, Biotechnology and Biotechnological Equipment

2004 - present   Editor, Zone4science

2003 - present   Visiting Professor, Fujian Medical University

2003 - 2005       Honorary Professor, Xiamen Medical University

2003 - present   Honorary Professor, Technical University of Varna

2002 - 2004       Visiting Professor, Wuhan Institute of Botany, Chinese Academy of Sciences

2002 - present   Editor, Technology in Cancer Research and Treatment

1992 - present   Journal Referee for: Cytobios, Adv. Molec. Biol, J. Cell Sci, Cell Biol. Int. Rep, Biol. Cell, C. R. Acad. Sci. Bulg, Oncologos, Medicine and Sport,  Biotechnol. & Biotechnol. Eq, Zone4science, Technology in Cancer Research and Treatment

Others

 2003 – 2012      Honorary Consul General for Bulgaria in Scotland

2007 - present   Chair, Slavic and Eastern European Institute, Scotland


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