Researcher

Associate Professor Laurence P. G. Wakelin

My Expertise

Extensive experience in teaching and research in medicinal chemistry and pharmacology in Universities in Australia, the United Kingdom, and Ireland. Particularly interested in drug discovery and development, intellectual property issues, DNA as a cancer drug target, and DNA damage and cancer. Experience as an expert witness in pharmaceutical patent infringement matters.

Keywords

Fields of Research (FoR)

Medicinal and Biomolecular Chemistry, Cancer and related disorders, Chemotherapy, Solid Tumours, Toxicology (incl. Clinical Toxicology), Intellectual Property Law

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Biography

Education

University of Kent, United Kingdom, BSc(Hons) 1st Class Chemistry 1971.

University of Cambridge, United Kingdom, PhD Pharmacology 1975.

Employment

Department of Pharmacology, University of Cambridge, Science Research Council Fellow 1975-1977.

Department of Pharmacology, University of Cambridge, Medical Research Council Fellow, 1978-1980.

Senior Scientist, Peter MacCallum Cancer Institute, Melbourne, 1981-1989.

Professor of Cancer...view more

Education

University of Kent, United Kingdom, BSc(Hons) 1st Class Chemistry 1971.

University of Cambridge, United Kingdom, PhD Pharmacology 1975.

Employment

Department of Pharmacology, University of Cambridge, Science Research Council Fellow 1975-1977.

Department of Pharmacology, University of Cambridge, Medical Research Council Fellow, 1978-1980.

Senior Scientist, Peter MacCallum Cancer Institute, Melbourne, 1981-1989.

Professor of Cancer Research, University College Dublin, 1990-1997.

Visiting Fellow, School of Chemistry, UNSW, 1998.

Associate Professor, School of Medical Sciences, UNSW, 1999-2019.

Appointed Honorary Associate Professor, School of Chemistry, UNSW, April 2019. 


My Grants

Total funds of $A3.5 million (at contemporary values) for studies of DNA-directed anti-cancer drugs. Sources include the UK Science Research Council, the UK Medical Research Council, the Australian Research Council, the Australian National Health and Medical Research Council, the Irish Research Council, the Irish Health Research Board, the Anti-Cancer Council of Victoria, the Association for International Cancer Research Scotland, and Cure Cancer Australia.


My Qualifications

BSc.(Hons) 1st Class Chemistry, University of Kent, UK, 1971.

PhD Pharmacology, Clare College, University of Cambridge, UK, 1975.


My Research Activities

Cancer is a disease that kills one in three of us. Practically all cytotoxic cancer drugs inhibit the biochemical functions of DNA, many doing so by binding to DNA directly. Our current research focusses on the discovery of novel DNA-targeted alkylating agents for the treatment of the brain tumours glioblastoma (GB) and cranial metastatic triple negative breast cancer (TNBC). These are particularly lethal cancers, in large part, because the tumour is shielded from drugs in the circulation by the blood brain barrier (BBB).

The BBB puts stringent restrictions on the physical properties of drugs that can access the brain by diffusion. For example, molecular weight must be less than 500 Daltons, lipophilicity should have a log P of about 2.5, the polar surface area should be less than 90 Å sq, and the drug should be weakly basic. We are developing agents which accord with these requirements, that are intended to kill GB and cranial TNBC cancer cells by inhibiting DNA replication as a result of crosslinking their DNA strands in novel ways that cells will find difficult to repair.

This is a collaborative effort involving the School of Chemistry, the Auckland Cancer Society Research Centre, and colleagues at University College London, and the University of Southampton. Here, in the School of Chemistry, the work involves ligand design by molecular modelling facilitated by docking and molecular dynamics; organic synthesis; and mass spectrometry, NMR, and spectrophotometric studies of ligand binding to DNA. Cytotoxicity and antitumour activity are evaluated by colleagues in Auckland, sequence selectivity, mechanisms of crosslinking and repair, and crystal structures of DNA-drug complexes are investigated by colleagues in the UK.

Current Major Collaborators

Associate Professor Graham Ball, School of Chemistry, UNSW.
Associate Professor Luke Hunter, School of Chemistry, UNSW.
Professor Martina Stenzel, School of Chemistry, UNSW.
Dr. Donald Thomas, School of Chemistry, UNSW.
Professor William A. Denny, Auckland Cancer Society Research Centre, New Zealand.
Professor Bruce Baguley, Auckland Cancer Society Research Centre, New Zealand.
Dr. Euphemia Leung, Auckland Cancer Society Research Centre, New Zealand.
Professor John Hartley, University College London.
Associate Professor Gary Parkinson, University College London.
Professor Keith Fox, University of Southampton.


My Research Supervision


Supervision keywords


Areas of supervision

I am available to supervise Honours and PhD students in the broad area of DNA-binding ligands, particularly those intended to be cytotoxic anticancer drugs. Such studies involve ligand design and synthesis, studies of the structure of DNA-ligand complexes by molecular dynamics, NMR spectroscopy, mass spectrometry, and spectrophotometric methods. Cytotoxicity and antitumour activity are evaluated by colleagues in Auckland, sequence selectivity, mechanisms of crosslinking and repair, and crystal structures of DNA-drug complexes are investigated by colleagues in the UK.


Currently supervising

Mr. Christopher Pracey (Joint supervisor with Associate Professor Graham Ball).
Ms. Jane Jung (Joint supervisor with Associate Professors Luke Hunter and Graham Ball).
Ms. Grace Constable (Joint supervisor with Associate Professors Luke Hunter and Graham Ball).
Mr. Adib Mohaimin (Joint supervisor with Associate Professors Luke Hunter and Graham Ball).
Mr. Daniel Weissberger (Joint supervisor with Associate Professors Luke Hunter and Graham Ball, and Professor Martina Stenzel).


My Engagement

Society Memberships

Fellow of the Royal Society of Chemistry, UK, FRSC

Fellow of the Royal Australian Chemical Institute, FRACI

Fellow of the Royal Society of New South Wales, FRSN

Member of the Australasian Society of Clinical and Experimental Pharmacology and Toxicology, ASCEPT

Member of the Intellectual Property Society of Australia and New Zealand, IPSANZ

Member of AusBiotech

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Location

School of Chemistry,
Dalton Building,
UNSW Sydney,
NSW 2052,
Australia,

Contact

+61414286217

Publications

by Associate Professor Laurence P. G. Wakelin

ORCID as entered in ROS