Dr Matthew Piggott completed his BSc and PhD at UWA working under the supervision of Prof. Dieter Wege on the total synthesis of natural products. He then took up a postdoctoral fellowship in the Research School of Chemistry at the Australian National University, where he worked on antibiotic drug discovery in collaboration with GlaxoSmithKline. His second postdoc, with Prof. T. Ross Kelly at Boston College, involved research directed at the synthesis of a chemically-powered, unidirectional molecular motor. Matthew was appointed to an academic position at the ANU in the Department of Chemistry in 2003, and moved to the School of Molecular Sciences at UWA in 2005.

Synthetic Organic Chemistry, Medicinal Chemistry and Chemical Biology

I love designing and synthesising new compounds. Sometimes this is done with a practical application in mind; for example, with the aim of discovering new drugs (medicinal chemistry), to study complex biological systems (chemical biology), or as molecular components of electronic circuits or machines. Sometimes, strategy and methodology are the focus: how can we make a complex, biologically active natural product as efficiently as possible? And, sometimes, the driving force is about pushing the boundaries. We can design molecules with unprecedented, beautiful structures – can we make them? In all cases, the creativity and logic of organic synthesis is immensely intellectually rewarding. Very brief overviews of current research areas are outlined below.

MDMA-inspired drug discovery: The psychedelic drug 3,4-methylenedioxymethamphetamine (MDMA) has recently been approved for assisted psychotherapy of post-traumatic stress disorder in Australia, on the back of highly successful phase III clinal trials. However, like any drug, it has some non-ideal properties that could be improved upon. In collaboration with our major partner Emyria Ltd. (https://emyria.com), we are investigating MDMA analogues for psychotherapy and novel treatments for various CNS indications. Our work in this area previously resulted in the discovery of UWA-121, a promising lead that enhances the duration and quality of levodopa therapy in Parkinson’s disease animal models.

Small molecule immunotherapy for cancer: Most mutated cells are recognised as such by the immune system and promptly dispatched. Only when they subvert the immune system do they become cancers. Immunotherapy, revolutionary treatment that reawakens the immune system to fight cancers, has minimal side-effects and can be lifesaving when it works. However, it is not effective in many cancer types, and even in responsive tumours, not all patients obtain benefit. Our aim is to extend game-changing immunotherapy to more cancer patients. In collaboration with cancer biologist A/Prof. Joost Lesterhuis (Telethon Kids Inst.), and structural biologist Prof. Alice Vrielink (UWA), we are investigating small molecule negative modulators of a nuclear receptor that is upregulated in many types of cancer. Genetic deletion or chemical inhibition of this receptor significantly improves response to immunotherapy in animal models. Hit-to-lead optimisation of two structurally distinct ligand classes is well underway and Setonix Pharmaceuticals (www.telethonkids.org.au/projects/setonix-pharmaceuticals-enhancing-immuno-oncology) has been spun-out to translate these findings to the clinic.

Reactive aldehyde trappers: In collaboration with Indiana based biotech company NeuroVigor Therapeutics (www.nvtherapeutics.com), A/Prof. Phil Burcham (Pharmacology, UWA) and I are exploring small sacrificial molecules that rapidly trap toxic aldehydes, which are implicated in the pathogenesis of many diseases and conditions, including spinal cord injury, neuropathic pain, multiple sclerosis, motor neuron disease and alcoholic liver disease. Proof of concept studies in animal models of neuropathic pain are currently underway.

Trypanosomiasis medicinal chemistry: Trypanosomiasis includes African sleeping sickness and Chagas disease, major neglected diseases of the third world. This work involves a multipronged international collaboration with Professor Jonathan Baell at the Monash Institute of Pharmaceutical sciences, Melbourne; Professor Vicky Avery at the Eskitis Institute, Griffith University, Brisbane; and GlaxoSmithKline, through the Tres Cantos Open Lab Foundation.

Chemical Biology: Efforts in this area have included the synthesis of stable analogues of phosphohistidine for the purpose of antibody generation, and histidine phosphatase/kinase inhibitor identification, in collaboration with Dr Paul Attwood (UWA, retired); the design and synthesis of fluorescent probes of enzyme activity; and biological mass-spectrometry probes for the interrogation of protein oxidation state with Professor Peter Arthur (UWA).

Total synthesis of natural products: Our group has achieved the total synthesis of >30 natural products, many of which have interesting biological activity. Total synthesis provides the ultimate validation of chemical structure, and our work has refuted and, in some cases corrected, several erroneous structure assignments. Our endeavours in this area provide material for further biological studies and inspire hypotheses about biological roles and biosynthetic pathways.

Design and synthesis of compounds with novel aromatic architectures: Work in this area includes the development of components for molecular electronics (with Professor George Koutsantonis), and the design and synthesis of novel and beautiful polycyclic aromatic compounds that have supramolecular application or resemble machine components.

For more details on any of these areas of research (see also "Current Projects"), please email Matthew.

Drug Discovery and Development
Pharmaceuticals
Natural products
Molecular electronics

Current Group Members:

Adam Wdowiak (PhD scholar, 2019–2023; submitted)
Heterotriangulenes (with George Koutsantonis, Chemistry, UWA)

Patrick James (PhD scholar, commenced 2020)
Natural products-inspired medicinal chemistry (with Dr Ern Lacey, Microbial Screening Technologies)

Sana Qureishi (PhD scholar, re-commenced 2021)
Trypanosomiasis medicinal chemistry and chemical biology

Louisa Tham (PhD scholar, commenced 2021)
Total synthesis of marine alkaloids

Jasmine King (PhD scholar, commenced 2022)
Covalent negative modulators of a nuclear receptor

Adam Fielding (PhD scholar, commenced 2023)

Next-gen MDMA analogues for psychotherapy

Dr Mark Walkey (Research Associate, MDMA-inspired drug discovery)

Dr Adrian Scaffidi (Senior Research Associate, Reversible negative modulators of a nuclear receptor)

Former Group members: (Current occupation)

Dr Craig Stewart (Research Associate 2023)

Design and Synthesis of PPAR ligands

Dr Joelie Han Chern Loh (Research Associate 2021–2023)

MDMA-inspired drug discovery

Dr Dominika Jusko (PhD 2018–2022)
Design and Synthesis of PPAR ligands

Valerio Falasca (Honours, 2020)
A radiotracer for Neutron capture-enhanced particle therapy (with ANSTO)

(PhD scholar UNSW)

Brianna Gordon (Honours, 2020)
A novel approach to spinal cord injury (with Phil Burcham, Pharmacology, UWA)
(Graduate Scientist, Dept. Agriculture, Water and Environment, Canberra)

Dr Glenn Pullella (PhD 2015–2020)
Total synthesis of bioactive peri-hydroxyquinone natural products

Research associate (2021–2023)

MDMA-inspired drug discovery

Dr Francis Dhoro (PhD 2015–2019)
Studies on the total synthesis of polycyclic aromatic alkaloids
(postdoctoral fellow, Oregon Health and Science University, USA)

Dr Harriet Newson (PhD, 2013–2017)
Part I: Highly oxygenated biphenyls inspired by natural products as antiviral agents Part II: Novel Trypanosomacidal agents for the treatment of human African Trypanosomiasis (HAT) and Chagas disease
(Senior Chemist, ChemCentre, Perth)

Dr Mark Walkey (Hons 2011, PhD 2012–2017, with Prof. George Koutsantonis)
Spiropyran-based organometallic molecular switches
(previously a postdoctoral fellow, University of Southampton)

Jesse Parkin-Gibbs (PhD 2009–2010, then with Prof. Murray Baker)
Structural identification of samoquasine A through total synthesis

Hannah Green (Honours 2016)
Total synthesis of dehydroxyarthrinone
(Analytical/forensic Chemist, ChemCentre WA, Perth)

Dr Stephanie Russell (PhD 2010-2016 with a period of suspension for family reasons)
MDMA analogues for the treatment of Blood Cancers; Hit-to-lead optimisation of a novel class of potent trypanosomacidal agents
(formerly Appili Therapeutics, Halifax, now a mother)

Pnelope Ng (Honours with Prof. Christina Chai, NUS)
Hit-to-lead optimisation of a novel class of potent trypansomacidal agents
(Associate analytical chemist, Covance, Singapore)

Dr Marco Buccini (Hons, PhD 2011-2015)
Part I. The total synthesis of epi-antrodioxolanone
Part II. Quinones as synthons for polycyclic, heteroaromatic natural products
(Senior Chemist, Imdex Ltd. Perth)

Rohan Joyce (Honours 2012)
Applications of stable analogues of phosphohistidines
(Synthetic chemist, Advanced Molecular Technologies, Melbourne)

Arthur Toynton (Honours level, on exchange from Durham U., 2012/2013)
African Sleeping sickness drug discovery
(Strategy Manager, Open Banking at HSBC UK Retail)

Shi Yuan Jeow (Honours 2011, Singapore)
Synthesis of alpkinidine analogues & Studies of a novel N-hydroxyindole synthesis
(Radiochemist, Clinical Imaging Research Center, A-STAR, Singapore)

Dr Shin Mukai (PhD 2007–2011)
Stable analogues of phosphohistidine
(CEO & CSO, New Wind Therapeutics)

Hung Nguyen (Hons 2006, PhD commenced 2007, w/d)
Parkinson’s disease med-chem

Dr Katie Punch (Hons, PhD 2005–2011)
Total synthesis of monosporascone and the antrocamphins
(Environmental Scientist, Alcoa)

Michael Gandy (Hons, PhD scholar, commenced 2006, w/d)
Redesigning the designer drug ‘ecstasy’: analogues of MDMA for the treatment of Parkinson’s disease and Burkitt’s lymphoma
(Student Services Manager, UNSW)

Dr Erik Jan Lindeboom (Occupational Trainee)
An improved, large scale synthesis of Leadfluor-1.
(Trainee Patent Attorney at V.O. Patents, Amsterdam)

David Osbourne (Honours 2009)
Polyacenes as bridging ligands for photoactive metal complexes.

Dr Katie Lewis (Honours, PhD 2005-2009)
Redesigning the designer drug ‘ecstasy’: analogues of MDMA for the treatment of Parkinson’s disease and Burkitt’s lymphoma

Collaborators:

Dr Ernest Lacey, Microbial Screening Technologies
Dr Joost Lesterhuis, Perkins Inst., UWA
Prof. Alice Vrielink, UWA
Prof. Vicky Avery, Griffith.
Prof. George Koutsantonis, UWA
Prof. Phil Burcham, Pharmacology/Pharmacy, UWA
Prof. Jonathan Baell, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne.

Former collaborators:

Prof. Peter Arthur, UWA.
Prof. Mathew Martin Iverson, UWA

Prof. Paul Attwood, UWA
Prof. Paul Low, UWA.
Prof. John Gordon, Birmingham University, UK
Prof. Christina Chai, National University of Singapore, Singapore.
Dr Jonathan Brotchie, University Health Network, Canada
A/Prof. Joanne Nash, University of Toronto, Canada
Dr Paul Besant, UWA