profile image for Dr Vadim Sumbayev

Dr Vadim Sumbayev

Senior Lecturer in Biochemistry and Interim Director of Research & Innovation

Medway School of Pharmacy

 

I obtained my PhD degree in Biochemistry in 1999 in Palladin Institute of Biochemistry NAS of UKraine. Then worked as assistant/associate professor at the Department of Biochemistry, Mechnikoff Odessa National University. In 2001 I obtained a highly competitive Humboldt Research Fellowship and moved to Germany (University of Kaiserslautern). Upon completion of my fellowship I spent three years in Aarhus (Denmark) working as assistant professor at the Interdisciplinary Nanoscience Centre, University of Aarhus. In December 2006 I joined Medway School of Pharmacy as a lecturer in Biochemistry.

Member of the NANOVAC consortium

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Current work of my research group is focused on the mechanisms of adaptation of human hematopoietic cells of myeloid lineage to different types of stress associated with low oxygen availability. This includes Toll-like receptor dependent inflammatory reactions, pro-allergic responses and progression of acute myeloid leukaemia. We investigate the role of hypoxia-inducible factor 1 transcription complex (HIF-1) and associated pathways in adaptation of human myeloid hematopoietc cells to stress taking place during the processes mentioned above. This includes studies of differential biochemical mechanisms of activation and functional role of HIF-1 in innate immune responses (Figure 1) and pathophysiological reactions of myeloid hematopoietic cells (Figure 2).

research fig 1

Figure 1. Biochemical mechanisms of HIF-1 activation during TLR signaling. Mechanisms leading to the accumulation and activation of HIF-1a protein during ligand-induced TLR7/8-mediated inflammatory process are presented (Nicholas, S. A. and Sumbayev, V. V. (2009) Cell Res. 19: 973-983; Sumbayev, V. V., Nicholas, S.A. (2010) Arch Immunol Ther Exp. 58:287-94 - Invited review).

research fig 2

Figure 2. Possible mechanisms of stem cell factor (SCF)-dependent HIF-1a accumulation in human myeloid leukaemia cells (Gibbs, B. F., Yasinska, I. M., Oniku, A. E. andSumbayev, V. V. (2011) PLoS One. 6: e 0022502.

Based on our understanding of these mechanisms and recent advances in Nanotechnology we are trying to apply gold nanoparticle-based Synthetic Biology approaches to specifically target HIF-1 transcription complex and associated pathways in human myeloid hematopoietic cells. This could allow pharmacological correction of pathophysiological reactions of these cells in cases of autoimmune disorders, allergic reactions and leukaemia progression.

Current Projects

  • The role of hypoxia-inducible factor 1 and its downstream signalling in biological responses of myeloid hematopoietic cells.
  • Applications of gold nanoparticle based Synthetic Biology for specific targeting of human myeloid cells.
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  • Yasinska IM, Gibbs BF, Lall GS, and Sumbayev VV. The HIF-1 transcription complex is essential for translational control of myeloid hematopoietic cell function by maintaining mTOR phosphorylation. (2014) Cell Mol. Life Sci., 71, 699-710.
  • Sumbayev VV, Yasinska IM, Garcia CP, Gilliland D, Lall GS, Gibbs B. F, Bonsall DR, Varani L, Rossi F, and Calzolai L. Gold Nanoparticles Downregulate Interleukin-1β-Induced Pro-Inflammatory Responses. (2013) Small, 9, 472-477.
  • Gibbs BF, Yasinska IM, Calzolai L, Gilliland D, and Sumbayev VV. Highly Specific Targeting of Human Leukocytes Using Gold Nanoparticle-Based Biologically Active Conjugates.  (2014) J. Biomed. Nanotechnol., 10, 1259-1266.
  • Gibbs BF, Yasinska IM, Pchejetski D, Wyszynski RW, and Sumbayev VV. Differential control of hypoxia-inducible factor 1 activity during pro-inflammatory reactions of human hematopoietic cells of myeloid lineage. (2012) Int. J. Biochem. Cell Biol.  44, 1739-1749
  • Sumbayev, V. V., Yasinska, I. M., Oniku, A. E., Streatfield, C. L., Gibbs, B. F. Involvement of Hypoxia-Inducible Factor-1 in the Inflammatory Responses of Human LAD2 Mast Cells and Basophils. (2012) PLoS One. 7(3): e34259.
  • Gibbs, B. F., Yasinska, I. M., Oniku, A. E., and Sumbayev, V. V. Effects of Stem Cell Factor on Hypoxia-Inducible Factor 1 alpha Accumulation in Human Acute Myeloid Leukaemia and LAD2 Mast Cells. (2011) PLoS One.6 (7) e 0022502.
  • Nicholas, S. A., Coughlan, K., Yasinska, I., Lall, G., Gibbs, B. F., Calzolai, L. andSumbayev, V. V. Dysfunctional mitochondria contain endogenous high-affinity human Toll-like receptor 4 (TLR4) ligands and induce TLR4-mediated inflammatory reactions. (2011) Int. J. Biochem. Cell Biol. 43, 674-681.
  • Nicholas, S. A., Bubnov, V. V., Yasinska, I. M. and Sumbayev, V. V. Involvement of xanthine oxidase and hypoxia-inducible factor 1 in Toll-like receptor 7/8-mediated activation of caspase 1 and interleukin-1beta. (2011) Cell Mol. Life Sci. 68, 151-158.
  • Pchejetski, D. Nunes, J., Coughlan, K., Lall, H., Pitson, S. M., Waxman, J. andSumbayev, V. V. The involvement of sphingosine kinase 1 in LPS-induced Toll-like receptor 4-mediated accumulation of HIF-1alpha protein, activation of ASK1 and production of the pro-inflammatory cytokine IL-6. (2010) Immunol. Cell. Biol. 89, 268-274.
  • Nicholas, S. A., Oniku, A., and Sumbayev, V. V. Myeloid cell death associated with Toll-like receptor 7/8-mediated inflammatory response. Implication of ASK1, HIF-1alpha, IL-1beta and TNF-alpha. (2010) Mol. Immunol. 48, 240-247.
  • Sumbayev, V. V., Nicholas, S. A. Hypoxia-inducible factor 1 as one of the “signalling drivers” of the Toll-like receptor-dependent and allergic inflammation. (2010) Arch. Immunol. Ther. Exp. - Invited review 58, 287-294.
  • Nicholas, S. A and Sumbayev, V. V. The role of redox-dependent mechanisms in the down-regulation of ligand-induced Toll-like receptor 7, 8 and 4-mediated HIF-1alpha prolyl hydroxylation. (2010) Immunol. Cell. Biol. 88, 180-186.
  • Sumbayev, V. V., Nicholas, S. A., Streatfield, C. L., Gibbs, B. F. Involvement of Hypoxia-Inducible Factor-1 in IgE-Mediated Primary Human Basophil Responses. (2009) Eur. J. Immunol. 39, 3511-3519.
  • Nicholas, S. A and Sumbayev, V. V. The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response. (2009) Cell. Res. 19, 973-983.
  • Lall H., Coughlan, K. and Sumbayev V. V. HIF-1alpha protein is an essential factor for protection of myeloid cells against LPS-induced depletion of ATP and apoptosis that supports Toll-like receptor 4-mediated production of IL-6. (2008) Mol. Immunol. 45, 3045-9.
  • Sumbayev V. V. LPS-induced Toll-like receptor 4 signalling triggers cross-talk of apoptosis signal-regulating kinase 1 (ASK1) and HIF-1alpha protein. (2008) FEBS Lett. 582, 319-326.
  • Sumbayev, V. V. Jensen, J. K., Hansen, J. A., Andreasen, P. A. Novel modes of oestrogen receptor agonism and antagonism by hydroxylated and chlorinated biphenyls, revealed by conformation-specific peptide recognition patterns. (2008) Mol. Cell. Endocrinol. 287, 30-39.
  • Sumbayev V. V. PI3 kinase and direct S-nitrosation are involved in down-regulation of apoptosis signal-regulating kinase 1 during LPS-induced Toll-like receptor 4 signalling. (2008) Immunol. Lett. 115, 126-130.
  • Sumbayev, V. V., Yasinska, I. M. Protein S-nitrosation in signal transduction. Assays for specific qualitative and quantitative analysis. Invited contribution (2008) Meth. Enzymol. 440, 209-219.
  • Hansen, J. A., Sumbayev, V. V., Gothelf, K. V. (2007) An electrochemical sensor based on the human estrogen receptor ligand binding domain. (2007) NANO Lett. 7, 2831-2834.
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Last Updated 20/11/2018