Oleksandr Zholos




Oleksandr Zholos

POSITION
Acting Head of Department of Biophysics and Medical Informatics, Educational and Scientific Centre “Institute of Biology and Medicine”

WORK EXPERIENCE
1981-2005
Research Assistant, Junior Research Scientist, Senior Research Scientist, Principal Research Scientist, Head of Laboratory of Molecular Pharmacology of Cellular Receptors and Ion Channels
National Academy of Sciences of Ukraine, Kyiv (Ukraine)

1990-1991
Visiting Scholar
Department of Physiology, College of Medicine, The Ohio State University, Columbus, Ohio (USA)

1991-2004
Research Fellow, Senior Research Fellow, Academic Visitor
Department of Pharmacology & Clinical Pharmacology, St. George's Hospital Medical School, London University, London (United Kingdom)

2001-2005
Visiting Professor
Laboratory of Cellular Physiology, Lille University of Science and Technology, Villeneuve d’Ascq (France)

2005-2006
Professor
Taras Shevchenko National University of Kyiv, Kyiv (Ukraine)

2006-2008
Director of Research
Cardiovascular Biomedical Research Centre, School of Medicine and Dentistry, Queen's University Belfast, Belfast (United Kingdom)

2006-2013
Chair in Vascular Physiology/Vascular Biology
Centre for Vision & Vascular Science, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast (United Kingdom)

2011 – Present
Professor
Taras Shevchenko National University of Kyiv, Kyiv (Ukraine)

2015 - Present
Acting Head of Department of Biophysics and Medical Informatics
Taras Shevchenko National University of Kyiv, Kyiv (Ukraine)

EDUCATION AND TRAINING


1976–1981
BSc (Biophysics) with Honours
Taras Shevchenko National University of Kyiv, Kyiv (Ukraine)

1987
PhD
National Academy of Sciences of Ukraine, Kyiv (Ukraine)

2000
Doctor of Science (Biophysics)
National Academy of Sciences of Ukraine, Kyiv (Ukraine)

2004
Senior Research Scientist
Higher Attestation Commission, Kyiv (Ukraine)

2005
Professeur des universités (Physiologie)
Ministry of Education, Higher Education and Research, Paris (France)

2014
Professor in Biophysics
Ministry of Education and Science of Ukraine, Kyiv (Ukraine)

Biophysical properties and functional roles of receptors and ion channels

Research Fields:
Molecular Biology & Genetics
Pharmacology & Toxicology
Biotechnology

Previous and Current Research

Prof. Zholos has long-standing interests in ion channel research and over 30 years of hands-on and supervisory experience in this area. This research employs patch-clamp recording techniques in combination with Ca2+ imaging and molecular biology approaches. It includes investigation of single ion channel mechanisms and the roles of multiple ligands in the regulation of novel TRP channels, as well as voltage-gated and receptor-operated channels in excitable and non-excitable cells.

Recent research highlights include identification of:

  • receptor-operated TRPC4 channels as the main molecular component of the muscarinic cation current in small intestine, which underlines cholinergic-excitation-contraction coupling in the gut;
  • molecular mechanisms of TRPC4 regulation;
  • enhanced expression and function of the heat and capsaicin receptor TRPV1 in severe bronchial asthma;
  • single-channel mechanisms of the cold and menthol receptor TRPM8 gating, as well as TRPM8 function in the vasculature;
  • biophysical and pharmacological characterisation of volume-regulated anion channels as an alternative pathway for chloride secretion in cystic fibrosis respiratory epithelial cells.

This research was funded by The Wellcome Trust (UK), British Heart Foundation (UK), National Institutes of Health (USA), NI Chest Heart & Stroke (Northern Ireland), Biotechnology and Biological Sciences Research Council (UK), The Royal Society (UK), The Physiological Society (UK), Mext (Japan), DEL (UK).

Ongoing research aims to develop novel activators of large-conductance Ca2+-activated potassium channels (maxi-K channels), which can be useful for the treatment of many disease states associated with hyperactivity of smooth muscles (e.g. hypertension, bronchial asthma, IBS). In particular, we have recently identified plasmonic gold nanocrystals (AuNCs) of ~5 nm core size having plasmon resonance of 532 nm as one class of potent maxi-K activators.


Figure 1. A schematic of study illustrating patch-clamp recording of Maxi-K channel activation by green laser-induced plasmon resonance (A) in an isolated arterial smooth muscle myocyte (B). In the cell-attached configuration, laser-illuminated AuNCs activate single Maxi-K channels in rat pulmonary artery myocytes in a remote manner (C).

Methodological and Technical Expertise

  • all variants of patch-clamp techniques (whole-cell and single channel recordings);
  • “sharp” microelectrode techniques;
  • calcium imaging using CCD camera and confocal microscopy;
  • flash photolysis of “caged” compounds;
  • ion channel expression and recording using two-microelectrode voltage clamp (Xenopus oocytes) and patch-clamp techniques (HEK-293 cells);
  • immunocyto/histochemistry, PCR and qRT-PCR;
  • data analysis using pClamp and MicroCal Origin software, custom programming:

Selected Publications

Research papers:

Kizub I.V., Pavlova O.O., Johnson C.D., Soloviev A.I., Zholos A.V.
Rho kinase and protein kinase C involvement in vascular smooth muscle myofilament calcium sensitization in arteries from diabetic rats.
British Journal of Pharmacology, 2010, 159, 1724-1731 (IF=5.259)

Fernández J.A., Skryma R., Bidaux G., Magleby K.L., Scholfield C.N., McGeown J.G., Prevarskaya N., Zholos A.V.
Voltage- and cold-dependent gating of single TRPM8 ion channels.
The Journal of General Physiology, 2011, 137, 173-195 (IF=4.511)

Miller M., Shi J., Zhu Y., Kustov M., Tian J.B., Stevens A., Wu M., Xu J., Long S., Yang P., Zholos A.V., Salovich J.M., Weaver C.D., Hopkins C.R., Lindsley C.W., McManus O., Li M., Zhu M.X.
Identification of ML204, a novel potent antagonist that selectively modulates native TRPC4/C5 ion channels.
Journal of Biological Chemistry, 2011, 286, 33436-33446 (IF=4.258)

Bidaux G., Beck B., Zholos A., Gordienko D., Lemonnier L., Flourakis M., Roudbaraki M., Borowiec A.-S., Fernández J., Delcourt P., Lepage G., Shuba Ya., Skryma R., Prevarskaya N.
Regulation of activity of Transient Receptor Potential melastatin 8 (TRPM8) channel by its short isoforms.
Journal of Biological Chemistry, 2012, 287, 2948-2962 (IF=4.258)

Fernández J.A., Skryma R., Bidaux G., Magleby K.L., Scholfield C.N., McGeown J.G., Prevarskaya N., Zholos A.V.
Short isoforms of the cold receptor TRPM8 inhibit channel gating by mimicking heat action rather than chemical inhibitors.
Journal of Biological Chemistry, 2012, 287, 2963-2970 (IF=4.258)

de Courcey F., Zholos A.V., Atherton-Watson H., Williams M.T., Canning P., Danahay H.L., Elborn J.S., Ennis M.
Development of primary human nasal epithelial cell cultures for the study of cystic fibrosis pathophysiology.
American Journal of Physiology – Cell Physiology, 2012, 303, C1173-1179 (IF=3.395)

McGarvey L.P., Butler C.A., Stokesberry S., Polley L., McQuaid S., Abdullah H., Ashraf S., McGahon M.K., Curtis T.M., Arron J., Choy D., Warke T.J., Bradding P., Ennis M., Zholos A., Costello R., Heaney L.G.
Increased expression of bronchial epithelial transient receptor 1 potential vanilloid 1 channels in severe asthma.
Journal of Allergy and Clinical Immunology, 2014, 133, 704-712 (IF=12.485)

Stott J.B., deCourcey F., Ennis M., Zholos A.V.
Functional and pharmacological characterization of volume-regulated anion channels in human normal and cystic fibrosis bronchial and nasal epithelial cells.
European Journal of Pharmacology, 2014, 740, 183-191 (IF=2.73)

Soloviev A., Zholos A., Ivanova I., Novokhatska T., Tishkin S., Raevska A., Stroyuk A, Yefanov V.
Plasmonic gold nanoparticles possess the ability to open potassium channels in rat thoracic aorta smooth muscles in a remote control manner.
Vascular Pharmacology, 2015, 72, 190-196 (IF=2.500)

Bidaux G., Sgobba M., Lemonnier L., Borowiec A.S., Noyer L., Jovonovic S., Zholos A.V., Haider S.
Functional and modelling studies of the transmembrane region of the TRPM8 channel.
Biophysical Journal, 2015, 109 (9), 1840-1851 (IF=3.632)

McGahon M.K., Fernández J.A., Dash D.P., McKee J., Simpson D.A., Zholos A.V., McGeown J.G., Curtis T.M.
TRPV2 channels contribute to stretch-activated cation currents and myogenic constriction in retinal arterioles.
Investigative Ophthalmology & Visual Science, 2016, 57 (13), 5637-5647 (IF=3.427)

Melanaphy D., Johnson C.D., Kustov M.V., Watson C.A., Borysova L., Burdyga T.V., Zholos A.V.
Ion channel mechanisms of rat tail artery contraction-relaxation by menthol involving, respectively, TRPM8 activation and L-type Ca2+ channel inhibition.
American Journal of Physiology – Heart & Circulatory Physiology, 2016, 311 (6), H1416-H1430 (IF=3.324)

Invited reviews and book chapters:

Zholos A.V.
Pharmacology of transient receptor potential melastatin (TRPM) channels in the vasculature.
British Journal of Pharmacology, 2010, 159, 1559-1571 (IF=5.259)

Zholos A., Johnson C., Burdyga T., Melanaphy D.
TRPM channels in the vasculature.
Advances in Experimental Medicine and Biology 704, 707-729 (IF=1.953)

Zholos A.
Studying endogenous TRP channels in visceral and vascular smooth muscles.
In “TRP channels”, Methods in Signal Transduction Series. Ed. M.X. Zhu, Boca Raton (FL): CRC Press, Taylor & Francis Group, 2011, 499 p., Chapter 9, 195-218.

Zholos A.V., Curtis T.M.
TRP channels in vascular disorders.
Current Topics in Medicinal Chemistry, 2013, 13, 295-309 (IF=3.402)

Zholos A.V.
TRPC5.
In “Mammalian Transient Receptor Potential (TRP) Cation Channels”, Handbook of Experimental Pharmacology, Eds. B. Nilius V. Flockerzi, Springer-Verlag Berlin Heidelberg, 2014, 222, 129-156.

Zholos A.V., McGarvey L., Ennis M.
TRPs in respiratory disorders: opportunities beyond TRPA1.
In: “TRP Channels as Therapeutic Targets: From Basic Science to Clinical Use”. Editor A. Szallasi. Elsevier, Academic Press, 2015, 536 pp., Chapter 26, 483-500.

Zholos A.V.
TRP channels in respiratory pathophysiology: the role of oxidative, chemical irritant and temperature stimuli.
Current Neuropharmacology 2015, 13 (2), 279-291 (IF=3.753)

Scopus                   ResearchGate                    ORCID

Contacts

Homepage: http://biology.univ.kiev.ua/ua/kafedra-biofiziki-vikladachi/656-zholos-oleksandr-viktorovich.html


a.zholos@univ.net.ua