Oleksandr Zholos




Oleksandr Zholos

POSITION
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

Department of Nerve-Muscle Physiology, A.A. Bogomoletz Institute of Physiology, 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

Department of Biophysics, Faculty of Biology, 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 – 2017

Professor, from 2015 Acting Head

Department of Biophysics and Medical Informatics, Educational and Scientific Centre “Institute of Biology”, Taras Shevchenko National University of Kyiv, Kyiv (Ukraine)

2017 – Present

Head of Department of Biophysics and Medical Informatics, Educational and Scientific Centre “Institute of Biology and Medicine”, 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 (Biophysics), A.A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv (Ukraine)

2000

Doctor of Science (Biophysics), A.A. Bogomoletz Institute of Physiology, 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.
  • nanostructured materials (e.g. C60 fullerenes) as novel modulators of BKCa and TRPC4 channels activity;
  • inhibitory action of inhalation anaesthetic isoflurane on the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions.

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), Department of Targeted Education of Taras Shevchenko National University of Kyiv at the National Academy of Sciences of Ukraine, and Ministry of Education and Science of Ukraine. 

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)

Feng J., Yang P., Mack M.R., Dryn D., Luo J., Gong X., Liu S., Oetjen L.K., Zholos A.V., Mei Z., Yin S., Kim B.S., Hu H. (2017).

Sensory TRP channels contribute differentially to skin inflammation and persistent itch.

Nature Communications, 2017, 8 (1), 980 (1-12) (IF= 11.878)

Dryn D., Luo J., Melnyk M., Zholos A., Hu H.

Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions.

European Journal of Pharmacology, 2018, 820, 39-44 (IF=3.170)

Dryn D.O., Melnyk M.I., Al Kury L.T., Prylutskyy Yu.I., Ritter U., Zholos A.V. (2018).

C60 fullerenes disrupt cellular signalling leading to TRPC4 and TRPC6 channels opening by the activation of muscarinic receptors and G-proteins in small intestinal smooth muscles.

Cellular Signalling, 2018, 43, 40-46 (IF=3.937)

Luo J., Qian A., Oetjen L.K., Yu W., Yang P., Feng J., Xie Z., Liu S., Yin S., Dryn D., Cheng J., Riehl T.E., Zholos A.V., Stenson W.F., Kim B.S., Hu H. (2018).

TRPV4 channel signaling in macrophages promotes gastrointestinal motility via direct effects on smooth muscle cells.

Immunity, 2018, 49(1), 107-119.e4 (IF= 19.734)

Melnyk M.I., Ivanova I.V., Dryn D.O., Prylutskyy Y.I., Hurmach V.V., Platonov M., Al Kury L.T., Ritter U., Soloviev A.I., Zholos A.V.

C60 fullerenes selectively inhibit BKCa but not KV channels in pulmonary artery smooth muscle cells.

Nanomedicine: Nanotechnology, Biology and Medicine, 2019, 19, 1-11 (IF=5.57)

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)

Storozhuk M.V., Zholos A.V.

TRP channels as novel targets for endogenous ligands: focus on endocannabinoids and nociceptive signalling.

Current Neuropharmacology, 2018, 16 (2), 137-150 (IF=4.568)

Moroz O., Zholos A.

Uterine myocytes: development, structure and function.

In: “Advances in Medicine and Biology”, Editor L.V. Berhardt, Nova Science Publishers, Inc., 2019, vol. 148, Chapter 2, 27-96.

Scopus                      ResearchGate                     ORCID                 Publons

Contacts

Homepage: Zholos


a.zholos@univ.net.ua

Phone: +38 (044) 522 08 27

International phone: 0038 (044) 522 08 27