Pavel Belan

P.V. Belan

PROF PAVEL BELAN

PH.D., DR.SCI.

PROFESSOR OF BIOPHYSICS

• Phone/Fax: +38044 2562053
• Skype: pavelbelan
• e-mail: pasha@biph.kiev.ua

Biography

Personal Statement

Degrees:

• M.Sc. (Applied Physics), 1985, Moscow Physics and Technology Institute, Moscow, USSR;
• Ph.D. (Biophysics), 1991, Bogomoletz Institute of Physiology, Kiev, USSR;
• Dr.Sci. (Biophysics), 2005, Bogomoletz Institute of Physiology, Kiev, Ukraine

Positions:

• 1985-1992: Research Assistant, Department of General Physiology of the Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine
• 1992-1993: Postdoctoral Fellow, Roche Institute of Molecular Biology, Nutley, NJ, USA
• 1993-1999: Scientific Researcher, Department of General Physiology of the Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine
• 1994-1999: Visiting Scientist, the University of Liverpool (Liverpool, UK), Helsinki University and Institute of Biotechnology (Helsinki, Finland), NIEHS, National Institutes of Health (Research Triangle Park, NC, USA)
• 1999-2012: Senior and Leading Scientific Researcher, Head of the Research Group, Department of General Physiology of the Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine
• 2004-2006: Visiting Scientist, Department of Physiology, the University of Liverpool, Liverpool, UK
• 2012-2017: Head of Laboratory of Molecular Biophysics, Department of General Physiology of the Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine

• Funded by International Science Foundation, British Royal Society, CRDF, The Wellcome Trust, STCU, SFFR, and NASU.

Current role

• Head of Department of Molecular Biophysics, Bogomoletz Institute of Physiology, Kiev, Ukraine.
• Funded by Horizon 2020, NIH, and NASU.
• Department of Molecular Biophysics

Current research interests

Signaling of neuronal Ca2+ sensor proteins.

This project is carried out in collaboration with Prof. Robert D Burgoyne and Dr. Lee Haynes (Neuronal Signalling group, University of Liverpool, UK), Prof. Alla Rynditch with group members (Institute of Molecular Biology and Genetics, Kiev, Ukraine), Dr. Venkat Venkataraman with group members (Rowan University, Glassboro, NJ, USA).

Analysis of the mechanisms underlying GABAergic synaptic transmission.

This project is carried out by our laboratory members.

Peripheral and central mechanisms of neuropathic pain.

This project is carried out in collaboration with Prof. Nana Voitenko (Department of Sensory Signaling) with group members, Prof. Yuriy Usachev with group members(University of Iowa, IA, USA) and Prof. Boris Safronov (IMCB, Porto, Portugal).

Personal Distinctions

• Roche Institute of Molecular Biology Fellowship Award (RIMB 1992)
• State Prizes of Ukraine in Science and Technology (State Prize Committee 2013)

Research

Summary of my scientific career

Current Research

My independent scientific career has been started in the early 2000 by studies centred on better understanding of modulation of GABAergic synaptic transmission and mechanisms of neuronal Ca2+-dependent signalling. Later on I have begun to study biophysical and physiological mechanisms of NCS (Neuronal Ca2+ Sensor) protein signalling in hippocampal neurons. Decoding of complex spatio-temporal patterns of [Ca2+]i changes by a Ca2+ sensor proteins, hippocalcin and neurocalcin δ, and involvement of Ca2+-dependent hippocalcin translocations in neuronal signal transduction is in a centre of this research. Molecular mechanisms underlying long-term depression and Ca2+-dependent potassium conductance in hippocampal neurons are studied in my laboratory now using a wide spectrum of optical (including FRET, FRAP, PA), electrophysiological and genetic approaches. Studying mechanisms shaping patterns of short-term plasticity in GABAergic synaptic connections between hippocampal neurons my laboratory have recently introduced two new statistical approaches that make it possible for the first time to accurately estimate biophysical properties of synaptic receptor channels from recordings of macroscopic postsynaptic currents. I have been also engaged in collaborative projects devoted to studies of peripheral and central mechanisms of neuropathic pain. In these projects we have shown how AMPA receptor trafficking and T-type Ca2+ channel modulation during chronic inflammation and diabetic neuropathy main contribute to changes in pain sensation.

Area of expertise

Calcium signaling in neurons and acinar cells; inhibitory and excitatory synaptic transmission; statistical analysis of microscopic currents; peripheral and central mechanisms of neuropathic pain; neuronal Ca2+ sensor protein signaling.

Research History

My scientific research began in the area of neuroscience during my studies toward M.Sc. and Ph.D. degrees at Moscow Institute of Physics and Technology (Moscow, USSR) and Bogomoletz Institute of Physiology (Kiev, USSR) in 1983-90. I used fluorescent microscopy and electrophysiological equipment with the goal to better understand mechanisms regulating intracellular cytoplasmic Ca2+ concentration changes in different types of excitable isolated cells. At the time, studies of these mechanisms in single neurons using fluorescent dyes were just started and were of great interest. No commercial equipment was available for this research and my colleague and I devised our own inverted microscopes and upgraded them with necessary light recording equipment based on low noise photomultipliers that we managed to obtain from a military plant. Utilizing this equipment resulted in publication of 13 papers during accomplishment of my Ph.D work, in which either my colleague or I were the first authors. Basically Ca2+ imaging studies were initiated in the USSR in these works under gentle and efficient supervision of our mentor, Prof. Platon Kostyuk. During my postdoc days I worked in the Department of Physiology (University of Liverpool) and this work resulted in developing several new techniques for an active clamp of Ca2+ concentration in neurons and measurement of Ca2+extrusion from single isolated cells. The latter of the methods was designed for direct visualization of Ca2+ extrusion sites from single cells. To detect Ca2+ extruded from the stimulated cells as well as to slow down diffusion of Ca2+ in the external milieu, we use confocal microscopy and a Ca2+ sensitive fluorescent probe linked to heavy dextran in the extracellular solution. We directly demonstrated that the secretory pole is the major Ca2+ extrusion site in pancreatic acinar cells following agonist stimulation and a substantial part of this efflux is due to calcium released from the secretory vesicles. Using modification of this approach applied to single secretory vesicles we show that second messengers cause rapid Ca2+ release from them, explaining the agonist-evoked cytosolic Ca2+ rise in the secretory pole. These methodologically advanced studies were possible due to complicated equipment that was on site owing to the Wellcome Trust equipment grant.

Research Grants

• 1994-1996 – ISF Long-Term Research Grant
• 1995-1996 – British Royal Society Joint Project Grant
• 1998-2000 – Ukrainian Biotechnology Grant
• 1999-2001 – CRDF Cooperative Grants Program Award
• 2002-2007 – The Wellcome Trust Collaborative Research Initiative Grant
• 2011-2013 – Science & Technology Center of Ukraine Project Grant
• 2011-2013 – State Key Laboratory Grants
• 2006-2014 – Functional Genomics Grant
• 2013–2016 – Grant NASU

Ongoing Research Support

• 2015–2019 – “New nanomaterials and nanotechnologies”, the National Academy of Sciences of Ukraine (NASU)
• 2017–2021 – “Cellular signaling systems in norm and pathology”, the National Academy of Sciences of Ukraine (NASU); together with other Heads of Departments
• 2019-2022 – "Pan-European twinning to re-establish world-level Neuroscience Centre in Kiev", Horizon 2020 - European Commission; together with Profs. G. Bakalkin, A. Konnerth, D. Rusakov, B. Safronov, N. Voitenko and G. Weiss
• 2019-2024 - "The Role of the Complement System in Spinal Mechanisms of Chronic Pain", National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA; together with Profs. Yu. Usachev and N. Voitenko

Selected Publications

• Osypenko, D. S. et al. Perturbed Ca2+-dependent signaling of DYT2 hippocalcin mutant as mechanism of autosomal recessive dystonia. Neurobiol. Dis. 104529 (2019). doi:10.1016/j.nbd.2019.104529
• Krotov, V., Tokhtamysh, A., Safronov, B. V., Belan, P. & Voitenko, N. High-threshold primary afferent supply of spinal lamina X neurons. Pain 1 (2019). doi:10.1097/j.pain.0000000000001586
• Cherkas, V. et al. Measurement of intracellular concentration of fluorescently-labeled targets in living cells. PLoS One 13, e0194031 (2018)
• Krotov, V. et al. Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation. Front. Cell. Neurosci. 11, 1–12 (2017)
• Shevchuk, D. P., Agashkov, K. S., Bilan, P. V & Voitenko, N. V. Spontaneous Synaptic Activity in Projection Neurons of Lamina I of the Isolated Rat Lumbar Spinal Cord : Effect of Peripheral Inflammation. Neurophysiology 49, 301–304 (2017)
• Kopach, O. et al. HIF-1α-mediated upregulation of SERCA2b: The endogenous mechanism for alleviating the ischemia-induced intracellular Ca(2+) store dysfunction in CA1 and CA3 hippocampal neurons. Cell Calcium 59, 251–61 (2016)
• Kopach, O., Krotov, V., Belan, P. & Voitenko, N. Inflammatory-induced changes in synaptic drive and postsynaptic AMPARs in lamina II dorsal horn neurons are cell-type specific. Pain 156, 428–38 (2015). PMID:25599231
• Duzhyy, D. E., Viatchenko-Karpinski, V. Y., Khomula, E. V, Voitenko, N. V & Belan, P. V. Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons. Mol. Pain 11, 29 (2015). PMID:25986602
• Khomula, E. V, Borisyuk, A. L., Viatchenko-Karpinski, V. Y., Briede, A., Belan, P. V & Voitenko, N. V. Nociceptive neurons differentially express fast and slow T-type ca(2+) currents in different types of diabetic neuropathy. Neural Plast. 2014, 938235 (2014). PMID:24693454
• Stepanyuk, A. R., Borisyuk, A. L., Tsugorka, T. M. & Belan, P. V. Different pools of postsynaptic GABAA receptors mediate inhibition evoked by low- and high-frequency presynaptic stimulation at hippocampal synapses. Synapse 68, 344–54 (2014). PMID:24677449
• Stepanyuk, A., Borisyuk, A. & Belan, P. Maximum likelihood estimation of biophysical parameters of synaptic receptors from macroscopic currents. Front. Cell. Neurosci. 8, 303 (2014). PMID:25324721
• Khomula, E. V, Viatchenko-Karpinski, V. Y., Borisyuk, A. L., Duzhyy, D. E., Belan, P. V & Voitenko, N. V. Specific functioning of Cav3.2 T-type calcium and TRPV1 channels under different types of STZ-diabetic neuropathy. Biochim. Biophys. Acta 1832, 636–49 (2013). PMID:23376589
• Kopach, O., Kao, S.-C. C., Petralia, R. S., Belan, P., Tao, Y.-X. X. & Voitenko, N. Inflammation alters trafficking of extrasynaptic AMPA receptors in tonically firing lamina II neurons of the rat spinal dorsal horn. Pain 152, 912–23 (2011). PMID:21282008
• Dovgan, a V, Cherkas, V. P., Stepanyuk, a R., Fitzgerald, D. J., Haynes, L. P., Tepikin, a V, Burgoyne, R. D. & Belan, P. V. Decoding glutamate receptor activation by the Ca2+ sensor protein hippocalcin in rat hippocampal neurons. Eur. J. Neurosci. 32, 347–58 (2010). PMID:20704590
• Belan, P. V & Kostyuk, P. G. Glutamate-receptor-induced modulation of GABAergic synaptic transmission in the hippocampus. Pflugers Arch. 444, 26–37 (2002). PMID:11976913
• Belan, P., Gardner, J., Gerasimenko, O., Gerasimenko, J., Mills, C. L., Petersen, O. H. & Tepikin, A. V. Isoproterenol evokes extracellular Ca2+ spikes due to secretory events in salivary gland cells. J. Biol. Chem. 273, 4106–4111 (1998). PMID:9606103
• Gerasimenko, O. V., Gerasimenko, J. V., Belan, P. V. & Petersen, O. H. Inositol trisphosphate and cyclic ADP-ribose-mediated release of Ca2+ from single isolated pancreatic zymogen granules. Cell 84, 473–480 (1996). PMID:8608601
• Belan, P. V, Gerasimenko, O. V, Tepikin, a V & Petersen, O. H. Localization of Ca2+ extrusion sites in pancreatic acinar cells. J. Biol. Chem. 271, 7615–9 (1996). PMID:8631796
• Belan, P., Kostyuk, P., Snitsarev, V. & Tepikin, A. Calcium clamp in isolated neurones of the snail Helix pomatia. J. Physiol. 462, 47–58 (1993). PMID:8392572
• Tepikin, A. V, Kostyuk, P. G., Snitsarev, V. A. & Belan, P. V. Extrusion of calcium from a single isolated neuron of the snail Helix pomatia. J. Membr. Biol. 123, 43–7 (1991). PMID:1774773

The rest of the publications can be found using PubMed search

Teaching

Supervision of PhD students

Current students:

• Mr. Eugen Sheremet
• Mr. Andrey Dromaretskiy

Recent PhD students:

• Dr. Volodymyr Krotov (2018)
• Dr. Alexandr Dovgan (2015)
• Dr. Anna Borisyuk (2014)
• Dr. Volodymyr Cherkas (2014)

Graduate and Undergraduate Courses

Current courses:

• Physiology of Complex Systems, Kiev PhTC of Moscow Institute of Physics and Technology (2015/2016)
• Biophysics of Complex Systems, National Technical University of Ukraine "Kyiv Polytechnic Institute” (2015/2016)
• Biophysics of Complex Systems, Taras Shevchenko National University of Kyiv (2015/2016)

External Engagement

Professional Membership

• Ukrainian Society for Neuroscience (Council member 2010 – up to date)
• P.G. Kostyuk Ukrainian Physiological Society (Member 2010 – up to date)
• Ukrainian Biophysical Society (Member 2014 – up to date)
• US Society for Neuroscience (Member 2001 – up to date)
• US Biophysical Society (Member 2003 – 2004)
• The Physiological Society, UK (Member 2009 – 2010)

Academic Roles Editorial Roles

• Ukrainian Physiological Journal, Fiziologichnyj Zhurnal (Editorial Board Member 2015 - )
• Neurophysiology (Kiev) (Reviewer 2003 - )
• PLOSone (Reviewer 2010 - )
• Synapse (Reviewer 2010 -)

External Examinations

• Institut de Neurobiologie de la Méditerranée, Marseille France (PhD 2010)
• Scientific Research Council for Defending of PhD Theses at Bogomoletz Institute of Physiology (Council member 2012 – up to date)
• Scientific Research Council for Defending of PhD Theses at Taras Shevchenko National University of Kyiv (Council member 2013 – up to date)