Pavel Belan

PROF PAVEL BELAN

PH.D., DR.SCI.

PROFESSOR OF BIOPHYSICS

• Phone/Fax:+380442562053

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

Current role is Head of Laboratory of Molecular Biophysics, Bogomoletz Institute of Physiology, Kiev, Ukraine.

Funded by STSU, SFFD, and NASU.

Department of General Physiology of the Central Nervous System

Laboratory of Molecular Biophysics

Current research interests

Signaling of neuronal Ca2+ sensor proteins. This project is carried out in collaboration with Prof.Robert D Burgoyne andDr. Lee Haynes (Neuronal Signalling group, Universityof Liverpool, UK), Prof. Alla Rynditc 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 using a new intact spinal cord preparation is a collaboration with Prof. Nana Voitenko (Laboratory 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 was started in the early 2000. After establishing my own research group, I have been engaged in a 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 pain. As a result of my collaboration established during accomplishment of the Wellcome Trust Collaborative Research Initiative Grant, 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 protein, hippocalcin, 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 possible for the first time accurate estimation of biophysical properties of synaptic receptor channels from macroscopic postsynaptic currents.

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

• 1994-96 - ISF Long-Term Research Grant (UBN200)
• 1995-96 – British Royal Society Joint Project Grant
• 1998-00 - Biotechnology Grant (Ukrainian Government)
• 1999-01- CRDF Cooperative Grants Program Award (UB2-2048 together with Prof. J.W. Putney)
• 2001 - IBRO Scholarship against Brain-Drain
• 2003 - IBRO Scholarship against Brain-Drain
• 2002-07 – The Wellcome Trust Collaborative Research Initiative Grant (069465/Z/02/Z, together with Prof. A. Tepikin)
• 2011-13 – Science & Technology Center of Ukraine (Project grant #5510)
• 2011-2013 - State Key Laboratory Grants (F46.2/001)
• 2006-2014 – Functional Genomics Grant (Ukrainian Government)

Ongoing Research Support

• 01/01/2013–12/31/2016-“Studies of genetically-determined molecular mechanisms of inter- and intracellular signaling in normal and pathological conditions”Grant NASU (# ІІ - 1- 12)

 

Publications

• 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. R., Belan, P. V & Kononenko, N. I. A model for the fast synchronous oscillations of firing rate in rat suprachiasmatic nucleus neurons cultured in a multielectrode array dish. PLoS One 9, e106152 (2014). PMID:25192180
• 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
• Borisyuk, A., Stepanyuk, A. & Belan, P. Activity-Dependent Potentiation of an Asynchronous Component of GABA-ergic Synaptic Currents in Cultured Hippocampal Neurons. Neurophysiology 46, 10–15 (2014).
• Kopach, O., Viatchenko-Karpinski, V., Atianjoh, F. E., Belan, P., Tao, Y. X. & Voitenko, N. PKCα is required for inflammation-induced trafficking of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons during the maintenance of persistent inflammatory pain. J. Pain 14, 182–192 (2013). PMID:23374940
• 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
• Morderer, D., Nikolaienko, O., Skrypkina, I., Cherkas, V., Tsyba, L., Belan, P. & Rynditch, A. Endocytic adaptor protein intersectin 1 forms a complex with microtubule stabilizer STOP in neurons. Gene 505, 360–4 (2012). PMID:22750298
• Kopach, O., Viatchenko-Karpinski, V., Belan, P. & Voitenko, N. Development of inflammation-induced hyperalgesia and allodynia is associated with the upregulation of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons. Frontiers in Physiology 3, (2012). PMID:23060815
• 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
• Stepanyuk, A. R., Borisyuk, A. L. & Belan, P. V. Efficient maximum likelihood estimation of kinetic rate constants from macroscopic currents. PLoS One 6, e29731 (2011). PMID:22242142
• 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
• Markova, O., Fitzgerald, D., Stepanyuk, A., Dovgan, A., Cherkas, V., Tepikin, A., Burgoyne, R. D. & Belan, P. Hippocalcin signaling via site-specific translocation in hippocampal neurons. Neurosci. Lett. 442, 152–7 (2008). PMID:18634855
• Shutov, L., Kruglikov, I., Gryshchenko, O., Khomula, E., Viatchenko-Karpinski, V., Belan, P. & Voitenko, N. The effect of nimodipine on calcium homeostasis and pain sensitivity in diabetic rats. Cell. Mol. Neurobiol. 26, 1541–57 (2006). PMID:16838100
• Markova, O., Stepanyuk, a., Tsugorka, T., Drebot, Y., Cherkas, V. & Belan, P. Applicability of Peak-Scaled Nonstationary Fluctuation Analysis to the Study of Inhibitory Synaptic Transmission in Hippocampal Cultures. Neurophysiology 37, 333–343 (2005).
• Stepanyuk, A. R., Boychuk, Y. A., Tsugorka, T. N., Drebot, Y. I., Lushnikova, I. V, Pivneva, T. A. & Belan, P. V. Estimating transmitter release rates and quantal amplitudes in central synapses from postsynaptic current fluctuations. Fiziol. Zh. 50, 22–32 (2004). PMID:15460024
• Ivanova, S. Y., Lushnikova, I. V, Pivneva, T. A., Belan, P. V, Storozhuk, M. V & Kostyuk, P. G. Differential properties of GABAergic synaptic connections in rat hippocampal cell cultures. Synapse 53, 122–30 (2004). PMID:15170824
• 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
• Storozhuk, M. V, Ivanova, S. Y., Pivneva, T. a, Melnick, I. V, Skibo, G. G., Belan, P. V & Kostyuk, P. G. Post-tetanic depression of GABAergic synaptic transmission in rat hippocampal cell cultures. Neurosci. Lett. 323, 5–8 (2002). PMID:11911977
• Stepanyuk, A., Chvanov, M. & Ivanov, A. Prolonged decay of evoked inhibitory postsynaptic currents in hippocampal neurons is not shaped by asynchronous release. Neurophysiology 34, 239–242 (2002).
• Storozhuk, M. V, Melnick, I. V, Kostyuk, P. G. & Belan, P. V. Postsynaptic mechanism may contribute to inhibitory acetylcholine effect on GABAergic synaptic transmission in hippocampal cell cultures. Synapse 41, 65–70 (2001). PMID:11354015
• in Measuring Calcium and Calmodulin Inside and Outside Cells (ed. Petersen, O. H.) 251–266 (Springer Berlin Heidelberg, 2001).
• Chvanov, M., Boychuk, Y. & Melnick, I. Distributions of interevent intervals for miniature inhibitory and excitatory postsynaptic currents in cultured hippocampal neurons. Neurophysiology 32, 90–92 (2000).
• Melnick, I. V, Chvanov, M. a & Belan, P. V. Rat hippocampal neurons maintain their own GABAergic synaptic transmission in culture. Neurosci. Lett. 262, 151–4 (1999). PMID:10218878
• 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
• Chvanov, M., Belan, P., Teslenko, V. & Mel’nik, I. Glutamate-induced suppression of inhibitory synaptic transmission in cultivated hippocampal neurons. Neurophysiology 30, 279–284 (1998).
• Belan, P., Gerasimenko, O., Petersen, O. H. & Tepikin, a V. Distribution of Ca2+ extrusion sites on the mouse pancreatic acinar cell surface. Cell Calcium 22, 5–10 (1997). PMID:9232347
• Belan, P. V., Saftenku, E. É., Gerasimenko, O. V., Pogorelaya, N. C., Chvanov, M. a. & Teslenko, V. I. Nonuniformity of calcium efflux from pancreatic acinar cells and its analysis by mathematical model of calcium diffusion and buffering in extracellular solution. Neurophysiology 29, 40–44 (1997).
• 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. V, Gerasimenko, O. V, Berry, D., Saftenku, E., Petersen, O. H. & Tepikin, A. V. A new technique for assessing the microscopic distribution of cellular calcium exit sites. Pflugers Arch. 433, 200–8 (1996). PMID:9019724
• Belan, P. & Saftenku, E. Mathemathical model of Ca2+ diffusion and buffering in extracellular solution after Ca2+ extrusion from a spherical cell. Neurophysiology 28, 187–192 (1996).
• Belan, P. V, Kiss, T., Snitsarev, V., Storozhuk, M. V & Osipenko, O. N. The effect of acetylcholine and serotonin on calcium transients and calcium currents in identified Helix pomatia L. neurons. Cell. Signal. 6, 551–9 (1994). PMID:7818991
• Belan, P. V, Kostyuk, P. G., Snitsarev, V. A. & Tepikin, A. V. Calcium clamp in single nerve cells. Cell Calcium 14, 419–25 (1993). PMID:8395337
• 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
• Diatlov, V. A., Belan, P. V, Bakaĭ, E. A., Makovetskiĭ, V. P. & Makovetskaia, V. V. [Tocopherol modulation of acetylcholine-induced current in mollusk neurons]. Neir̆ofiziologiia = Neurophysiol. 23, 628–31 (1991). PMID:1664914
• Györi, J., Kiss, T., Shcherbatko, A. D., Belan, P. V, Tepikin, A. V, Osipenko, O. N. & Salánki, J. Effect of Ag+ on membrane permeability of perfused Helix pomatia neurons. J. Physiol. 442, 1–13 (1991). PMID:1665853
• 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
• Belan, P. V & Osipenko, O. Blocking effect of La3+ ions on transmembrane ionic current evoked by intracellular cyclic AMP injection in identified Helix pomatia neurons. Neurosci. Lett. 124, 137–9 (1991). PMID:1649979
• Kostyuk, P. G., Belan, P. V & Tepikin, A. V. Free calcium transients and oscillations in nerve cells. Exp. brain Res. 83, 459–64 (1991). PMID:1708727
• Belan, P. V, Osipenko, O. N. & Tepikin, A. V. Inositol-1,4,5-trisphosphate and non-hydrolysable GTP analogue induced calcium release from intracellular stores of the Helix pomatia neurons. Comp. Biochem. Physiol. C. 96, 45–7 (1990). PMID:1980882
• Belan, P. V, Verkhratskiĭ, A. N., Pronchuk, N. F. & Tepikin, A. V. [Use of a microfluorometric method for measuring free calcium in the cytoplasm of isolated cultured rat cardiomyocytes]. Fiziol. Zh. 35, 39–45 (1989). PMID:2612622
• Belan, P. V, Osipenko, O. N. & Tepikin, A. V. [Calcium release from the intracellular stores of the soma of the mollusk neuron under the action of inositol triphosphate and its nonhydrolyzable analog GTP]. Neir̆ofiziologiia = Neurophysiol. 21, 707–10 (1989). PMID:2601771
• Belan, P., Mironov, S., Osipenko, O. & Tepikin, A. Changes produced in intracellular calcium concentration and transmembrane currents by iontophoretic injection of cAMP in Helix pomatia neurons. Neurophysiology 21, 291–296 (1989).
• Belan, P. V, Dolgaia, E. V, Mironov, S. L. & Tepikin, A. V. [Relation between the surface potential of mouse neuroblastoma clone C1300 cells and the phase of the cell cycle]. Neir̆ofiziologiia = Neurophysiol. 19, 130–3 (1987). PMID:3033525
• Kostyuk, P., Tepikin, A., Belan, P. & Mironov, S. MECHANISMS OF CYTOPLASMIC CA-2+ CHANGES IN SNAIL NEURONS MEDIATED BY INTRACELLULAR CA-2+ STORES. Biol. Membr. 4, 932–36 (1987).

Teaching

Supervision of PhD students

Current students:

• Mr. Eugen Sheremet
• Mr. Andrey Dromaretskiy
• Mr. Maxim Matveenko
• Mr. Volodymyr Krotov

Recent PhDstudents:

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

Graduate and Undergraduate Courses

Current courses:

• Biophysics 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 BiophysicalSociety(Member 2014 – up to date)
• US Society for Neuroscience (Member 2001 – up to date)
• USBiophysical Society (Member 2003 – 2004)
• The Physiological Society, UK (Member 2009 – 2010)

Academic Roles Editorial Roles

• Ukrainian Physiological Journal, Fiziologichnyj Zhurnal (Editorial Board Member 2015 - )
• PLOSone (Reviewer2010 - )
• Synapse (Reviewer2010 -)

External Examinations

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