Area of Study / Keywords

Pharmacology Enzymology Enzyme inhibitors Pharmacokinetics Pharmacology education

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About

B.Sc. (Hons) in Pharmacology, Department of Pharmacology, University of Dundee, Scotland (1989)

M.Phil. in Pharmacology, Department of Pharmacology, University of Cambridge (Queens' College), England (1990)

Ph.D. in Pharmacology, Department of Pharmacology, University of Cambridge (Queens' College), England (1993)

Neurodiverse Scottish pharmacologist, enzymologist. Settler on Treaty 6 territory. Advocate for collegial governance and academic freedom. Socialist; votes for political parties that value education, healthcare and social programs and support society's most vulnerable. Married with two grown-up sons. Licensed football (soccer) coach (retired), player (should retire) and lifelong supporter of Dundee United F.C. Road cyclist. Woodworker. Wine snob. Likes dogs, birds, IPA. Dislikes rudeness, ignorance, selfishness and dishonesty.

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Research

Pharmacology of enzymes, particularly flavin-containing monoamine oxidases and copper-containing primary amine oxidases. Use of steady-state and transient state (stopped-flow) kinetic approaches and ligand binding techniques to understand mechanisms of catalytic interactions between ligands and enzymes.

Novel approaches to the teaching of pharmacokinetics and pharmacodynamics.

We are available for collaboration with researchers who require expertise in enzyme kinetic analyses.

EXAMPLE PUBLICATIONS

HOLT, A. (2018) On the practical aspects of characterising monoamine oxidase inhibition in vitro.  J. Neural Transm., 125, 1685-1705.

ZUNA, I. & HOLT, A. (2017)  ADAM, a hands-on patient simulator for teaching principles of drug disposition and compartmental pharmacokinetics.  Br. J. Clin. Pharmacol., 83, 2426-2449.

FATEHI, M.,CARTER, C.R.J., YOUSSEF, N., HUNTER, B.E., HOLT, A. & LIGHT, P.E. (2015) Molecular determinants of ATP-sensitive potassium channel Mg-ATPase activity: diabetes risk variants and diazoxide sensitivity.  Biosci. Rep., 35, e00238.

KOZUSKA, J.L., PAULSEN, I.M., BELFIELD, W.J., MARTIN, I.L., COLE, D.J., HOLT, A. & DUNN, S.M.J. (2014)  Impact of intracellular domain flexibility upon properties of activated human 5-HT3receptors.  Br. J. Pharmacol., 171, 1617-1628.

RAMSAY, R.R., OLIVIERI, A. & HOLT, A. (2011)  An improved approach to steady-state analysis of monoamine oxidases. J. Neural Transm., 118, 1003-1019.

KACHALOVA, G., DECKER, K, HOLT, A. & BARTUNIK, H.D. (2011)  Crystallographic snapshots of the complete reaction cycle of nicotine degradation by an amine oxidase of the monoamine oxidase family. Proc. Nat. Acad. Sci. (USA), 108(12), 4800-4805.

McDONALD, G.R., OLIVIERI, A., RAMSAY, R.R. & HOLT, A. (2010)  On the formation and nature of the imidazoline I2binding site on human monoamine oxidase-B.  Pharmacol. Res., 62, 475-488.

BONIVENTO, D., MILCZEK, E.M., McDONALD, G.R., BINDA, C., HOLT, A., EDMONDSON, D.E. & MATTEVI, A. (2010)  Potentiation of ligand binding through cooperative effects in monoamine oxidase B. J. Biol. Chem., 285(47), 36849-36856.

McDONALD, G.R., HUDSON, A.L., DUNN, S.M., YOU, H., BAKER, G.B., WHITTAL, R.M., MARTIN, J.W., JHA, A., EDMONDSON, D.E. & HOLT, A. (2008)  Bioactive contaminants leach from disposable laboratory plasticware. Science, 322, 917.

HOLT, A., SMITH, D.J., CENDRON, L., ZANOTTI, G., RIGO, A. & DI PAOLO, M.L. (2008) Multiple binding sites for substrates and modulators of semicarbazide-sensitive amine oxidases: kinetic consequences.  Mol. Pharmacol., 73(2), 525-538.

HOLT, A. & PALCIC, M.M. (2006)  A peroxidase-coupled continuous absorbance platereader assay for flavin monoamine oxidases, copper-containing amine oxidases and related enzymes.  Nature Protocols, 1(5), 2498-2505.

HOLT, A., ALTON, G., SCAMAN, C.H., LOPPNOW, G.R., SZPACENKO, A., SVENDSEN, I. & PALCIC, M.M. (1998)  Identification of the quinone cofactor in mammalian semicarbazide-sensitive amine oxidase.  Biochemistry, 37(14), 4946-4957.

HOLT, A. & BAKER, G.B. (1996)  Inhibition of rat brain monoamine oxidase enzymes by fluoxetine and norfluoxetine.  Naunyn-Schmiedeberg’s Arch. Pharmacol., 354, 17-24.

FUNDING

My research has been supported by:

The Canadian Institutes of Health Research (CIHR)

The Canada Foundation for Innovation (CFI)

The Alberta Diabetes Institute (ADI)

The University of Alberta Teaching and Learning Enhancement Fund (TLEF)

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Teaching

I teach principles of pharmacodynamics and pharmacokinetics in the MD curriculum Foundations block (MED511), renal pharmacology in the MD/DDS program (DMED517), introductory pharmacodynamics and pharmacokinetics in the BPharm program (PHARM203), and metabolism of psychiatric drugs in the Pharmacy graduate program (PHARM630).

I am the Pharmacology lead on the Teaching Committee of the Wenzhou Medical University, Alberta Institute.

I am developing a series of short animated vodcasts to explain pharmacokinetic and pharmacodynamic principles to students in the health sciences.

AWARDS AND RECOGNITION

The Rang Prize (2018), an international award presented by the British Pharmacological Society for contributions to the teaching of Pharmacology.

The Lecturer Excellence Award (2018) presented by the Medical Students' Association for an outstanding contribution to the teaching of medicine.

The Department of Psychiatry Education Committee Teaching Award (2020)