Personal profile

Biography

Tim Hales graduated with a BSc (Hons) in Physiology from King’s College London in 1986 and a PhD from the University of Dundee in 1990. He completed postdoctoral training in the Department of Anesthesiology, University of California in Los Angeles and in 1997 was appointed Assistant Professor at the George Washington University in Washington DC where he gained tenure in 2002.  He became Professor in the Departments of Pharmacology and Anesthesiology & Critical Care Medicine and Director of Research in Anesthesiology at GWU in 2006.

 

Tim returned to Dundee in 2009 as Professor of Anaesthesia and non-clinical head of the Division of Neuroscience.  He was elected Fellow of the Royal College of Anaesthetists in 2011 and was appointed Associate Dean for Research-Led Teaching in the School of Medicine in 2017. His research group studies the mechanisms of action of anaesthetics and opioid analgesics, drugs that modulate neuronal communication through ion channel modulation. The group’s work on metastatic colon cancer cells identified voltage-activated Na+ channels as potential targets for anticancer medications. Inhibition of these channels by local anaesthetics inhibits cell invasion.

 

Tim’s goal is to improve anaesthesia and analgesia by 1) educating future researchers and anaesthetists and 2) by identifying molecular targets responsible for the desirable and detrimental effects of anaesthetics and analgesics. His research has received support by grants from Tenovus Scotland, the National Science Foundation and the National Institutes of Health, USA and the National Institute of Academic Anaesthesia, UK.

Research interests

Pain was an unavoidable consequence of injury, disease and infection before the advent of clinical anaesthesia. Now, thanks to skilled anaesthetists, pain-ameliorating analgesics and general anaesthetics (GAs), millions of people undergo surgery every year and most recover with relatively minor discomfort. While only a small minority of patients experience major negative consequences all anaesthetics have side effects. Most cause respiratory depression and some may cause neurodegeneration, a particular concern in the elderly. Analgesic agents also have severe side effects. Opioids such as morphine and fentanyl are commonly used to treat both perioperative and chronic pain; however their prolonged use leads to physical dependence and a loss of potency due to tolerance. Morphine can also cause hyperalgesia, a paradoxical increase in pain. There is a pressing need to develop better GAs and analgesics.

We are studying the mechanisms of action of opioids and GAs, drugs that influence neuronal excitability by binding to membrane proteins and thereby directly or indirectly regulating the activity of ion channels. By identifying the proteins responsible for their therapeutic and detrimental effects we hope to offer a strategy for improved safety and efficacy.

Opioid receptors (mu, delta and kappa) couple through G proteins to effectors, including K+ and Ca2+ channels. Morphine activates mu receptors thereby inhibiting Ca2+ channels, reducing excitatory transmission within the pain pathway. Prolonged morphine exposure leads to analgesic tolerance. Tolerance is attenuated in mice that lack beta-arrestin2, a protein that interacts with the mu receptor affecting its internalization and coupling it to signalling proteins including the tyrosine kinase, c-Src. We are testing the hypothesis that tolerance requires c-Src activity using electrophysiological recording and measurements of analgesia in mice.

Morphine induced hyperalgesia occurs in opioid receptor knock-out mice and is therefore independent of opioid receptor activation. We are using electrophysiological recording and behavioural assays to test the hypothesis that opioids directly modulate the activity of ion channels (e.g. the 5-HT3 receptor) and that these “off-target” actions contribute to their side effect profiles.

Research that began in the 1980’s in Dundee revealed that GAs, such as the induction agent propofol, enhance neuronal inhibition by the neurotransmitter gamma-aminobutyric acid (GABA) through a direct interaction with the GABAA receptor. GABA activates the GABAA receptor opening the integral Cl- channel and this activity is enhanced by GAs. The GABAA receptor is the primary target for induction agents. Since the 1980’s genes that encode 19 different GABAA receptor subunits have been cloned revealing considerable receptor heterogeneity. We identified the GABAA receptor epsilon subunit which reduces the enhancement of GABAA receptor function by GAs. The epsilon subunit may protect specific brain regions from inhibition by GAs. We are exploring the subtype specificity of GAs. Using chimeric constructs of the epsilon subunit and mutagenesis we are characterizing the nature of the GA interaction with the GABAA receptor.

Mutations in GABAA genes can profoundly affect the GA sensitivity of GABAA receptors. The artificial introduction of mutant receptors that are resistant to GA modulation makes mice resistant to immobilization by propofol validating GABAA receptors as the primary target of induction. We use homology modelling, mutagenesis and electrophysiological techniques to examine the relationship between structure and function of GABAA receptors and other related Cys-loop receptors. We recently demonstrated that mutations in individuals with epilepsy, which reduce GABA efficacy, enhance potentiation by propofol.

Teaching

2009-present    Level 3 and 4 Pharmacology and Neuroscience BSc and BMSc lectures in anaesthesia, anti-epileptics, drug dependence and opioids, University of Dundee

2009-present    Supervision of BSc (Hons) and BMSc research projects.

2006-2009       Neurobiology 212: Lecturer - Introduction to neurobiology: freshman medical students. The George Washington University (GWU)

2005-2009       Pharmacology 170: Lecturer - Introduction to Pharmacology & Toxicology for undergraduate pharmacogenomics students. GWU

2004-2009       Pharmacology 202: Lecturer - Antiepileptic drugs: sophomore medical students. GWU

2000-2009       Pharmacology 502: Lecturer - Clinical use of drugs for 4th year medical students. GWU

2000-2009       Pharmacology 207: Lecturer - Pharmacology for GWU Physician Assistant students.

2006-2009       Mol. Medicine 280: Advanced neuropharmacology/neurophysiology for graduate students.

2005-2009       Biomed Sci 214: Lecturer - Cell Biology: receptors and ion channels. Graduate students.

1998-2009       Pharmacology 201: Lecturer - Pharmacology for sophomore medical students. Lectures on drugs of abuse, alcohol, general anesthetics, local anesthetics, anxiolytics and anticonvulsants. GWU

1998-2009       Pharmacology 201: Instructor - Autonomic pharmacology labs. GWU

1998-2006       Neuroscience 285: Course Director and lecturer - Neurophysiology for graduate students

1997- 2009      Pharmacology 205: Lecturer - Pharmacology lectures to graduate students. GWUMC.

1997-2009       Pharmacology 280: Lecturer - Pharmacology lectures to graduate students. GWUMC.

1997-2009       Biochemistry 280: Lecturer - Neurochemistry lectures to graduate students. GWUMC.

1997                HC66: Substance Abuse & the Brain. Lecturer - Honors Collegium. UCLA undergraduates.

1997                Neurobiology 101: Lecturer - Introduction to Molecular Neurobiology. UCLA undergraduates.

1995-1997       Cell & Tissue Neurobiology 209B: Lecturer - Neuronal electrophysiology. UCLA Access Graduate Students.

1994-1995       Neuroscience M202: Lecturer/Instructor - Receptors of Inhibitory Amino Acids. Lectures to 1st year UCLA IDP Neuroscience Graduate students.

1994                Neuroscience M211A . Lecturer – Neurodegeneration. UCLA Neuroscience Graduate Students.

1993-1996       Neuroscience 275A: Lecturer - Advanced Techniques in Neurobiology to 2nd year UCLA IDP Neuroscience Graduate students.

1992                Pharmacology 237A: Lecturer - Electrophysiology Lectures, 2nd year UCLA Pharmacology Graduate Dept. Pharmacology, UCLA.

1990-1992       Neuropharmacology Lecturer to Anesthesiology Residents. Dept. Anesthesiology, UCLA.

1986-1989       Instructor for the 2nd, 3rd and 4th year Neuropharmacology classes. Dept. Pharmacology, DundeeUniversity.

 

Fingerprint Fingerprint is based on mining the text of the person's scientific documents to create an index of weighted terms, which defines the key subjects of each individual researcher.

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Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Research Output 2005 2018

  • 28 Article
  • 3 Editorial
  • 2 Book/Film/Article review
  • 1 Review article
1 Citations

Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription: a primary care data linkage study

Torrance, N., Mansoor, R., Wang, H., Gilbert, S., Macfarlane, G. J., Serpell, M., Baldacchino, A., Hales, T. G., Donnan, P., Wyper, G., Smith, B. H. & Colvin, L. Jun 2018 In : British Journal of Anaesthesia. 120, 6, p. 1345-1355 11 p.

Research output: Contribution to journalArticle

Information Storage and Retrieval
Benzodiazepines
Chronic Pain
Opioid Analgesics
Prescriptions

Menthol reduces phototoxicity pain in a mouse model of photodynamic therapy

Wright, L., Baptista-Hon, D., Bull, F., Dalgaty, F., Gallacher, M., Woods, J. A., Ibbotson, S. H. & Hales, T. G. 1 Feb 2018 In : PAIN. 159, 2, p. 284-297 13 p.

Research output: Contribution to journalArticle

Menthol
Phototoxic Dermatitis
Photochemotherapy
Action Potentials
Pain

Loop G in the GABAA receptor α1 subunit influences gating efficacy

Baptista-Hon, D. T., Gulbinaite, S. & Hales, T. G. 1 Mar 2017 In : Journal of Physiology. 595, 5, p. 1725-1741 16 p.

Research output: Contribution to journalArticle

Open Access
File
Propofol
gamma-Aminobutyric Acid
GABA Receptors
Bicuculline
GABA-A Receptors
Open Access
File
Ventral Tegmental Area
mu Opioid Receptor
Morphine
Inhibitory Postsynaptic Potentials
Neurons
1 Citations

Src Kinase Inhibition Attenuates Morphine Tolerance without Affecting Reinforcement or Psychomotor Stimulation

Bull, F. A., Baptista-Hon, D. T., Sneddon, C., Wright, L., Walwyn, W. & Hales, T. G. Nov 2017 In : Anesthesiology. 127, 5, p. 878-889 12 p.

Research output: Contribution to journalArticle

src-Family Kinases
Morphine
Pleasure
Opioid Analgesics
Analgesics

Prizes

Fellow of the Royal College of Anaesthetists

Timothy Hales (Recipient), 2012

Prize: Election to learned society

Activities 2015 2015

  • 1 Types of Public engagement and outreach - Schools engagement

Neurobiology and Communication Advanced Higher Lecture

Hales, T. (Presenter)
4 Mar 2015

Activity: Types of Public engagement and outreach - Schools engagement

Press / Media

Opinion on the use of cognitive enhancing drugs

Timothy Hales

3/09/17

1 item of media coverage

Press/Media: Other

Thesis

Development of a high throughput ligand screening method and structural studies of pentameric ligand gated ion channels.

Author: Trumper, P., 2014

Supervisor: B. (Supervisor) & Hales, T. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File

Neurosteroids: endogenous analgesics?

Author: Humble, S. R., 2013

Supervisor: Lambert, J. (Supervisor), Hales, T. (Supervisor) & Belelli, D. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Science

File

Targeting Opioid Receptor Signal Transduction to Produce Sustained Analgesia

Author: Bull, F. A., 2015

Supervisor: Hales, T. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File

The Mechanism of Action of Lidocaine and Levobupivacaine on Human Cardiac Voltage-gated Na+ Channels NaV1.5

Author: Elajnef, T. R., 2016

Supervisor: Hales, T. (Supervisor)

Student thesis: Master's ThesisMaster of Science

File