Bogdan Amuzescu

Position

Associate Professor

Affiliation

Dept Biophysics&Physiology, Faculty of Biology,

University of Bucharest, Romania

Phone

+40 731 695 749

E-mail

bogdan@biologie.kappa.ro

Education

  • 1972-1976, Elementary school no. 80 in Bucharest

  • 1976-1980, Secondary school (gymnasium) no. 117 in Bucharest

  • 1980-1984, "Nicolae Balcescu" college in Bucharest (former and present St. Sava National College), mathematics physics class; Diploma

  • 1985-1991, Faculty of Medicine of the "Carol Davila" University of Medicine and Pharmacy in Bucharest; Diploma

  • 1999-2000, Master in neurobiology, University of Bucharest

  • 2000-2003, PhD, Faculty of Biology, University of Bucharest; thesis title: "Properties of ion channels in biomembranes" Supervisor: Prof. Maria-Luisa Flonta, Co-promotors: Prof. Willy van Driessche, Prof. Gordon Reid

  • 2000-2003, Research fellowship, Dept Mol. Cell Biol, Faculty of Medicine, KU Leuven (Prof. Willy van Driessche)

  • 2003-2004, Postdoctoral research fellowship, Cardiac Electrophysiology Group, Center for Experimental Surgery & Anaesthesiology, KU Leuven (Prof. K. Mubagwa)

Experience

  • 1991-1992, Stagiary physician in Constanta Departmental Hospital, Laboratory of Nuclear Medicine and Ist Medical Clinic

  • 1991-1992, Associated assistant in the Department of Biophysics, Biotechnology, Medical Informatics and Biostatistics, Faculty of Medicine, "Ovidius" University, Constanta

  • 1992-1994, Secondary physician (specialization in clinical hematology) in Fundeni Hospital, Clinic of Hematology

  • 1994-1995, Secondary physician (specialization in internal medicine) in Bucharest University Hospital, IInd Medical Clinic

  • 1995-2000, Specialist physician (internal medicine) in Bolintin Hospital

  • 2000-2002, Assistant Lecturer, Dept. Biophysics & Physiology, Univ. of Bucharest

  • 2002-2005, Lecturer, Dept. Biophysics & Physiology, Univ. of Bucharest

  • 2005-present, Associate Professor, Dept. Biophysics & Physiology, Univ. of Bucharest

  • 2014 -2015,Application Scientist, Cytocentrics Bioscience GmbH, Rostock, Germany

Specialities

  • Mathematical modeling & analysis of complex biological systems (heart, neuronal networks)

  • Membrane biophysics and transport phenomena in biomembranes

  • Thermodynamics of biological systems

  • Molecular electrophysiology & pharmacology - the patch-clamp technique

  • Thermotransduction, nociception and pain

  • Molecular pathophysiology and experimental models of various diseases: inflammatory and neuropathic pain, diabetic neuropathy, neuronal and myocardial ischemia, Alzheimer's disease

  • Cardiomyocyte electrophysiology, modeling and pharmacology; Cardiac safety pharmacology

Achievements

  • set up of a system for delivery of thermal stimuli to cells during patch-clamp recordings and/or ion imaging experiments, followed by a detailed study of the effects of cooling on capsaicin- or protonelicited TRPV1 currents in cultured dorsal root ganglia primary sensory neurons

  • description and analysis of a biphasic effect of Zn2+ on native and heterologously expressed epithelial Na+ channels (ENaC)

  • study of permeation, gating, and regulation properties of a nonselective cation current in ventricular myocytes inhibited by intracellular magnesium and blocked by extracellular divalent and trivalent cations (IMIC – magnesium-inhibited cation current) leading to its identification as TRPM7, and proof of its role in heavy metal ion transport, intracellular Mg2+ homeostasis, and activation by exogenous free oxygen radicals

  • study of the permeation and gating properties of ASIC1a, analysis of single-channel recordings and validation of an 8-state linear connectivity Markov model for gating, correlation analysis of adjacent events durations, demonstration of an effect of extracellular trypsin on Ca2+ permeability and on activation by amitriptyline and FMRF-amide; the activatory effect of low concentrations of amitriptyline (within the therapeutical range) on ASIC1a conductance and gating, evidenced in whole-cell and single-channel experiments, may contribute to the well-known but incompletely understood analgesic effect of tricyclic antidepressants

  • set up of detailed electrophysiology models for cardiomyocytes from different cardiac territories starting from a reduced compartmented model of guinea pig ventricular cardiomyocyte (Faber-Rudy 2007) comprising Markov models for the L-type Ca2+ channel and ryanodine receptor and Ca2+ dynamics between various intracellular compartments (network and junctional sarcoplasmic reticulum, bulk myoplasm, and the “subspace” between t tubules and junctional sarcoplasmic reticulum), to be further used for “in silico” models of human heart electrophysiology and pharmacology

  • mathematical study of an early ventricular cardiomyocyte model (Luo-Rudy I 1991) using the tools of dynamic systems analysis and bifurcation theory, for different values of model parameters, and finding configurations of parameters leading to sustained oscillations, important in defining arrhythmogenic mechanisms

  • automated patch-clamp recordings on hiPSC-cardiomyocytes, development of a patented complex in vitro pharmacology assay on hiPSC-CM integrating all the 3 stages of the CiPA paradigm, study of proarrhytmogenic risk predictors and arrhythmogenesis mechanisms for several drugs, including chloroquine and hydrohychloroquine, cenobamate

  • exploration of the cellular and molecular mechanisms of photobiomdulation with NIR laser and biophoton emmission

  • over 140 presentations at international and internal scientific meetings, over 21 presentations published in abstract in international ISI-quoted journals, over 39 published scientific articles, 6 books/book chapters, 4 patents, >365 citations, h-index 12 (WOS)/685 citations, h-index 15 (Google Academic)

Publications

  1. Reid G., Amuzescu B., Zech E., Flonta M.-L. (2001): A system for applying rapid warming or coolingstimuli to cells during patch clamp recording or ion imaging. J Neurosci Methods 111(1):1-8.

  2. Babes A., Amuzescu B., Krause U., Scholz A., Flonta M.-L., Reid G. (2002): Cooling inhibits capsaicininduced currents in cultured rat dorsal root ganglion neurones. Neurosci Lett. 317(3):131-134.

  3. Amuzescu B., Ion S., Popescu D., Movileanu L., Avram S., Macri B., Flonta M.-L. (2002): Thermallgroup motion creates stochastic pores in plane phosphatidylcholine bilayers. Romanian J Biophys. 12 (1-2): 37-52.

  4. Pena F., Neaga E., Amuzescu B., Nitu A., Flonta M-L (2002): Amitriptyline has a dual effect on theconductive properties of the epithelial Na channel. J Pharm Pharmacol. 54:1393-1398.

  5. Amuzescu B., Segal A., Flonta M-L., Simaels J., Van Driessche, W. (2003): Zinc is a voltagedependent blocker of native and heterologously expressed epithelial Na+ channels. Pflügers Arch. 446: 6977.

  6. Gwanyanya A., Amuzescu B., Zakharov S., Macianskiene R., Sipido K., Bolotina V., Vereecke J.,Mubagwa K. (2004): Magnesium-inhibited, TRPM6/7-like channels in cardiac myocytes: permeation of divalent cations and pH-mediated regulation. J Physiol. 559(3): 761-776.

  7. Neaga E., Amuzescu B., Dinu C., Macri B., Pena F., Flonta M.-L. (2005): Extracellular trypsin increasesASIC1a selectivity for monovalent versus divalent cations. J Neurosci Methods 144: 241-248.

  8. Pena F., Amuzescu B., Neaga E., Flonta M.-L. (2006): Thermodynamic properties of hyperpolarizationactivated current (Ih) in a subgroup of primary sensory neurons, Exp Brain Res., 173(2):282-290. [09] Marin A., Prica C., Amuzescu B., Neaga E., Flonta M.-L. (2008): ASIC1a activation by amitriptyline and FMRF-amide is removed by serine proteases, Channels (6):419-428.

  9. Popescu D., Popescu A.G., Amuzescu B. (2010): Pulsatory liposomes - a possible biotechnologicaldevice for controlled drug delivery. I. The liposome swelling. Rom J Biophys. 20(1):37-46.

  10. Popescu D., Popescu A.G., Amuzescu B., Maries E. (2010): Pulsatory liposomes - a possiblebiotechnological device for controlled drug delivery. II. The pore appearance, Rom J Biophys. 20(2):171181.

  11. Popescu A.G., Popescu D., Ion S., Amuzescu B. (2010): Pulsatory liposomes - a possiblebiotechnological device for controlled drug delivery. III. The liposome relaxation, Rom J Biophys. 20 20(3):223-234.

  12. Bichir C.L., Georgescu A., Amuzescu B., Nistor G., Popescu M., Flonta M.-L., Corlan A.D., Svab I.(2011): Limit cycles by FEM for a one-parameter dynamical system associated to the Luo-Rudy I model, ROMAI J. 6(2):27-39.

  13. Corlan A.D., Amuzescu B., Milicin I., Iordachescu V., Poenaru E., Corlan I., De Ambroggi L. (2011): Intercellular conductance variability influences early repolarization potentials in a myocardial tissue model with stochastic architecture, Advanced Topics in Electrical Engineering (IEEE Proceedings, ISSN 20687966):1-4. http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?arnumber=5952183

  14. Chioncel V., Paun D., Amuzescu B., Sinescu C. (2012): Evolution features of hypertensive patientswith primary aldosteronism - prospective study, J. Med. Life 5(3): 354-359.

  15. Kusko M., Craciunoiu F., Amuzescu B., Halitzchi F., Selescu T., Radoi A., Popescu M., Simion M.,Bragaru A., Ignat T. (2012): Design, fabrication and characterization of a low-impedance 3D electrode array system for neuro-electrophysiology, Sensors (Basel) 12(12):16571-16590.

  16. Amuzescu B., Georgescu A., Nistor G., Popescu M., Svab I., Flonta M.-L., Corlan A. (2012): Stabilityand sustained oscillations in a ventricular cardiomyocytes model, Interdisciplinary Sciences: Computational Life Sciences 4(1):1-18.

  17. Amuzescu B., Scheel O., Knott T. (2014): Novel automated patch-clamp assays on stem cell-derived cardiomyocytes: will they standardize in vitro pharmacology and arrhythmia research? J Phys Chem.

Biophys. 4(4):153 http://dx.doi.org/10.4172/2161-0398.1000153

  1. Chevalier M., Amuzescu B., Gawali V., Todt H., Knott T., Scheel O., Abriel H. (2014): Late cardiacsodium current can be assessed using automated patch-clamp, F1000Research http://f1000research.com/articles/3-245/v1

  2. Scheel O., Frech S., Amuzescu B., Eisfeld J., Lin K.-H., Knott T. (2014): Action potentiall characterization of human induced pluripotent stem cell-derived cardiomyocytes using automated patchclamp technology, Assay Drug Dev Technol. 12(8):457-69

  3. Halitzchi F., Jianu L., Amuzescu B. (2015): Electrophysiology and pharmacology study of a humanneuroblastoma cell line, Rom. Rep. Phys. 67(2):439-451

  4. Iordache F., Constantinescu A., Andrei E., Amuzescu B., Halitzchi F., Savu L., Maniu H. (2016): Electrophysiology, immunophenotype, and gene expression characterization of senescent and cryopreserved human amniotic fluid stem cells, J. Physiol. Sci. 66:463-47http://link.springer.com/article/10.1007/s12576-016-0441-8/fulltext.html

  5. Filippi A., Caruntu C., Gheorghe R.O., Deftu A., Amuzescu B., Ristoiu V. (2016): Catecholaminesreduce TRPV1 desensitization in cultured dorsal root ganglia neurons, J. Physiol. Pharmacol. 67(6):843850

  6. Amuzescu B., Cocina G., S. Florica (2016): Miniature electrode array and system for experimentalsurface EEG recordings, Rom. J. Biophys. 26(2):69-82 http://www.rjb.ro/articles/445/RJB2-2016_a1.pdf

  7. Amuzescu B., Airini R., Ghica L., Epureanu F.B., Deftu A.F., Cucu D.M., Ristoiu V.P., Mihailescu D.F., Radu B.M. (2017): Novel approaches to proarrhythmogenic risk testing using automated patch-clamp platforms, Rom. J. Biophys. 27(1):13-22 http://www.rjb.ro/articles/449/Amuzescu-2_SH.pdf

  8. Mann S.A., Heide J., Knott T., Airini R., Epureanu F.B., Deftu A.-F., Deftu A.-T., Radu B.M., Amuzescu B. (2019): Recording of multiple ion current components and action potentials in human induced pluripotent stem cell-derived cardiomyocytes via automated patch-clamp, J. Pharmacol. Toxicol. Meth. 100:106599

  9. Airini R., Iordache F., Alexandru D., Savu L., Epureanu F.B., Mihailescu D., Amuzescu B., Maniu, H. (2019): Senescence-induced immunophenotype, gene expression and electrophysiology changes in human amniocytes, J. Cell. Mol. Med. 23(11):7233-7245

  10. Iacobas S., Amuzescu B., Iacobas D.A. (2021): Transcriptomic uniqueness and commonality of the ion channels and transporters in the four heart chambers, Sci. Rep. 11(1):2743

  11. Amuzescu B., Airini R., Epureanu F.B., Mann S.A., Knott T., Radu B.M. (2021): Evolution of mathematical models of cardiomyocyte electrophysiology, Math. Biosci. 334:108567

  12. Deftu A.T., Amuzescu B. (2022) Protective Effects of Nanosof® Suspension on Cultured Cells Exposed to H2O2, Biointerface Research in Applied Chemistry 12(2):2548-2559 https://biointerfaceresearch.com/?page_id=8308, https://doi.org/10.33263/BRIAC122.25482559

  13. Thomet U., Amuzescu B., Knott T., Mann S.A., Mubagwa K., Radu B.M. (2021): Assessment of proarrhythmogenic risk for chloroquine and hydroxychloroquine using the CiPA concept, Eur. J. Pharmacol. 913:174632

  14. Coman A., Amuzescu B., Nistor G. (2023): Theoretical Assumptions in Conductivity and Dielectric Properties Assessment of Biological Tissues - Errors and Resulting Consequences, IEEEXplore® 2023 13th International Symposium on Advanced Topics in Electrical Engineering (ATEE) (https://ieeexplore.ieee.org/document/10108270)( https://doi.org/10.1109/ATEE58038.2023.10108270)

  15. Shaher S.A.A., Galateanu B., Hudita A., Maitham A., Mihailescu D.F., Amuzescu B. (2023): An in vitro model of aspartame cytotoxicity via heterologous expression of NMDA receptors, Farmacia 71(3):581-590 https://doi.org/10.31925/farmacia.2023.3.17

  16. Shaher S.A.A., Mihailescu D.F., Amuzescu B. (2023): Aspartame safety as a food sweetener and related health hazards, Nutrients 15:3627 (28 p.)

  17. Iordache F., Petcu (Ionescu) A., Pisoschi A.M., Stanca L., Geicu O.I., Bilteanu L., Curutiu C., Amuzescu B., Serban A.I. (2024): PCR array profiling of miRNA expression involved in the differentiation of amniotic fluid stem cells toward endothelial and smooth muscle progenitor cells, Int. J. Mol. Sci. 25(1):302 (14 p.) https://doi.org/10.3390/ijms25010302

  18. Amuzescu B., Corlan A.D., Radu B. (2023): Inhibitory effects of cenobamate on multiple human cardiac ion channels and possible arrhythmogenic consequences, (in preparation for resubmission, preprint available at https://www.researchsquare.com/article/rs-3735338/v1)


Patents

Iacobas A.D., Amuzescu B., Ciontu Cristina: Manufacturing procedure for micropipettes for single-channell recordings in biomembranes - Patent RO-102203/06.10.1988

Iacobas A.D., Amuzescu B.: Procedure and device for cleaning patch-clamp micropipettes - Patent RO-

108844/04.11.1991

Amuzescu B., Radu B.M., Mihailescu D.F., Mann S.: Method for in vitro detection of the proarrhythmogenic risk of a drug candidate on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) - EPO patent application EP18465611/24.10.2018

Amuzescu B., Radu B.M., Mihailescu D.F., Mann S.: Method for in vitro detection of the proarrhythmogenic risk of a drug candidate on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) - USPTO patent application US2020/01326601/ filed 10.10.2019, published 30.04.2020

Books

Amuzescu B, Avram S, Macri B: Lucrari practice de biofizica, Editura Universitatii din Bucuresti, 2005, ISBN 973575980-2

Amuzescu B, Mubagwa K: Cardiac Ion Channels and Transporters, in From Vascular Cell Biology to

Cardiovascular Medicine, A. Georgescu, F. Antohe (eds.), Research Signpost, Kerala, 2011, ISBN 978-817895-503-2

Amuzescu B, Istrate B, Musat S: Channelopathies and Heart Disease, in Cardiac Arrhythmias: from Basic

Mechanisms to State-of-the-art Management, A.S. Kibos et al. (eds.), Springer, 2014, ISBN 978-1-44715315-3

Amuzescu B, Corlan D, Nistor G: Modelarea matematica a electrofiziologiei cardiace, Editura Universitatii din Bucuresti, 2012, ISBN 978-606-16-0145-5

Amuzescu B: Modelarea matematica a sistemelor biologice complexe, in Problema minte-creier in neurostiinta cognitiei, G. Vacariu, G. Stefanov (eds.), Editura Universitatii din Bucuresti, 2013, ISBN 978606-16-0224-7

Amuzescu B., Istrate B., Mubagwa K: Impact of Cellular Mechanisms of Ischemia on CABG Failure, in Coronary Graft Failure: State-of-the-Art, Ion C. Tintoiu, Malcolm John Underwood, Stephane Pierre Cook,

Hironori Kitabata, Aamer Abbas (eds.), Springer, New York, 2016, ISBN 978-3-319-26515-5

Invited lectures/chairmanship

Effects of different transitional elements (groupVIIIb-IIb) and of certain lanthanides on the apical Na+ channels of A6 cells. BIL 96 symposium, KU Leuven, 2000.

Extracellular trypsin improves Na+ selectivity of ASIC1a, presentation at Sensing Physiology : a

Symposium on Biosensors and Cell Physiology, Limburgs Universitair Centrum, Diepenbeek, December 5, 2003.

Magnesium-inhibited, TRPM6/M7 like channels in cardiomyocytes: divalent cation permeation and pHmediated regulation. Neuroscience 2005 International Symposium Timisoara-München, Timisoara, 14-15 October, 2005.

Magnesium-inhibited TRPM6/M7 like channels in cardiomyocytes. 2nd International Conference of the Romanian Neuroscience Society, Bucharest, 1-3 September, 2006.

Co-chair (with Dr. Thomas Dierk, Heidelberg Univ.), Platform session BC: Cardiac electrophysiology, 53rd Biophysical Society Annual Meeting, Boston, March 4, 2009.

Myocardial TRPM7 channels: biophysical properties and involvement in cardiac diseases. 3rd International Conference on Clinical & Experimental Cardiology, Chicago, April 15-17, 2013

Diaryldiamidines Interaction with ASIC1a as a Basis for Novel Pharmacological Targets in Neuronal Ischemia, Drug Discovery for Ion Channels XIV - Satellite Meeting to 58th Biophysical Society Meeting, San Francisco, CA, 14 Feb 2014

A New CiPA-compliant Cardiac Safety Pharmacology Automated Patch-Clamp Assay, Ncardia Applications Workshop 2018, Cologne, November 7-9 2018, abstract p. 13

In vitro and in silico cardiac safety drug testing: advancing the CiPA paradigm, invited lecture within the CIVIS Summer School “Drug Design and Discovery”, Dept. Pharmacy, School of Health Science, National and Kapodistrian University of Athens, July 4-8, 2022

Academic activities

Coordination/Technical program committee

Coordinator of the Group of Mathematical Modeling of Complex Biological Systems, part of the Research

Center in Neurobiology, Department of Biophysics&Physiology, Faculty of Biology, University of Bucharest (http://neurobiologie.ro/en/Research-Themes-Electrophysiology-and-Mathematical-Modeling-of-ExcitableSystems/)

2001-present: Teaching staff & co-organizer of the Master in Neurobiology Programme, Department of Biophysics & Physiology, Faculty of Biology, University of Bucharest (http://www.bio.unibuc.ro)

2006-2008: Coordinator of Grant CNCSIS A 1030/2006 - "Modulation of ENaC/Deg ion channels by intracellular divalent cations and their roles in neuronal ischemia-putative pharmacological targets in stroke therapy"

2004-2012: Advisory board, Romanian Society of Neuroscience, Bucharest, Romania

2015-: advisory board, Romanian Society aginst Epilepsy

Professional membership: Biophysical Society, American Association for the Advancement of Science, Federation of American Societies for Experimental Biology, Federation of European Neuroscience Societies,

Romanian Society of Pure and Applied Biophysics, Romanian Society for Physiology, Romanian Society for Neuroscience, Romanian Society against Epilepsy (Romanian chapter of ILAE)

Reviewer/EB member

European Journal of Pharmacology, European Journal of Biophysics, Journal of Neuroscience Methods,

Central European Journal of Biology, American Journal of Modern Physics, Natural Products Chemistry &

Research

Courses

  • neurobiophysics

  • anatomy&physiology

  • data processing

  • clinical diagnosis & therapy

Projects

2001-2004, Volkswagen Foundation research grant: "Generation of spontaneous activity in damaged nerve: novel experimental approaches" (135000 EUR)

2000-2002, NATO grant CLG976246 "Mechanisms of diabetic neuropathic pain in the primary sensory neurone" (20000 USD)

2003-2004, Postdoctoral research grant - Dept. Exp. Surgery&Anaesthesiology, KULeuven, Belgium (15000 EUR)

2002-2003, CERES 1/3/2002 "In vitro study of changes within the intracellular signaling network during energy deprivation stress" (10000 EUR)

2003-2005, VIASAN 199/2003 "Modulation mechanisms of ion channels activated by tissue acidosis in peripheral nerve fibers and blood vessels" (50000 EUR)

2005-2008, CEEX 67/2005 "Health protection by development of new complex instruments (laboratory-ona-chip)" (28570 EUR)

2006-2007, CNCSIS 1030/2006 "Modulation of ENaC/Deg ion channels by intracellular divalent cations and their roles in neuronal ischemia-putative pharmacological targets in stroke therapy" (22857 EUR) (grant coordinator)

2005-2010, CEEX 3191/2005 "Molecular, cellular, and integrated pain mechanisms-medical applications" (100000 EUR)

2007-2010, PNCDI2 Cooperation Grant 61-010/2007 "Mathematical modeling of the electrical activity of neurons and cardiomyocytes - isolated and in tissue - applied to prediction of arrhythmia and response to antiarrhythmics" (500000 EUR)

2012-2016, PNCDI2 Cooperation Grant 80/2012 "Cellular Therapeutic Approaches for Regenerative Stroke Therapy" (465000 EUR) (partner coordinator)

2016-2019, POC EU-funded structural grant P_37_675 “Development of automated patch-clamp technologies for pro-arrhythmogenic risk testing of drug candidates” (~1000000 EUR)

2022-2024, PCE grant 39/2022: PN-III-P4-PCE-2021-1422 “Drug safety profiles of two newly-aproved antiepileptics by in vitro screening for pro-arrhythmogenic risk and BBB drug transport” (250000 EUR)