Dr Andrew Montgomery

Dr Andrew Montgomery, Drug Discovery Initiative Postdoctoral Fellow, The University of Sydney.

Andrew received a Bachelor of Medicinal Chemistry Advanced with first class honours from the University of Wollongong in 2014. In 2015, he received an Australian Government Research Training Program Award scholarship to undertake a PhD under the supervision of A/Prof. Danielle Skropeta and A/Prof. Haibo Yu at the University of Wollongong. Andrew’s research was focused on the design and synthesis of sialyltransferase inhibitors to generate novel anti-metastatics. Andrew received his PhD in 2019, and later that year took up a position as a Drug Discovery Initiative Postdoctoral Fellow, working under the supervision of Prof. Michael Kassiou at the University of Sydney. As part of his ongoing role in Prof. Kassiou’s research group, Andrew’s research is focussed on small molecule synthesis and computational studies for a variety of CNS based projects in the areas of inhibiting neurotoxic protein aggregation, developing diagnostics and therapeutics targeting neuroinflammation and alleviating social dysfunction.

Forefront Group:

  • USYD Medicinal Chemistry and Drug Discovery Research Group

Neurodegeneration of interest:

Frontotemporal dementia, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis

Expertise:

  • Medicinal chemistry
  • Computational Chemistry
  • PET tracer development

Affiliate Organisations

USyd

Specific Skills:

  • Synthetic organic chemistry
  • Hit-to-lead drug discovery
  • Drug development
  • Radiotracer development
  • Molecular Docking Calculations
  • Molecular Dynamics Simulations
  • Free Energy Calculations
  • NMR spectroscopy
  • Mass spectrometry

Project - Drug discovery for diagnosis and treatment of frontotemporal dementia syndromes

All Chief investigators and associate investigators

CIA: Prof Michael Kassiou, CIB: Dr Jonathan Danon, AIA: Dr Eryn Werry, AIB: Dr Andrew Montgomery

Research Project Abstract

Frontotemporal dementia (FTD) is a common cause of early-onset dementia, with near comparable prevalence to Alzheimer’s disease (AD) for 45–55 year-olds. Drug discovery efforts to significantly stall, halt, or reverse brain damage have struggled badly over the past 20 years. Our research focuses on 1) developing molecular tools for studying the early stages of diseases like FTD (with potential for earlier diagnosis, aiding patient recruitment) and 2) discovery of new small molecules that reduce the damaging effects of protein aggregation in the CNS.

Disease area:

FTD, ALS, AD

Challenges within the field

There are currently no disease-modifying treatments for neurodegenerative diseases on the market. Our research program aims to provide better information for drug discovery scientists through development of more sensitive methods for early diagnosis of such diseases. We judiciously choose novel biological targets with therapeutic potential and use a combination of computational, medicinal chemistry, and pharmacology expertise to validate their role in neurodegeneration.

Research Project Description

The ultimate goals of this project are to discover novel chemical entities that display genuine translational promise for the diagnosis and treatment of FTD and other neurodegenerative diseases. To achieve these goals, we employ a multi-pronged approach encompassing medicinal chemistry, in silico modelling, and in vitro pharmacological testing. Projects include:

  • Structure-based design of new drugs for restricting or halting the destructive effects of tau protein aggregation, either directly or through kinase activation/inhibition or chaperone manipulation
  • Design and optimisation of new drugs for reducing or resolving TDP-43 protein aggregation, either directly or through chaperone manipulation
  • Innovative discovery of sensitive and universal positron-emission tomography (PET) tracers for dissecting microglial contributions to FTD (e.g. pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes)
  • Discovery of new small molecules that inhibit damaging neuroinflammatory pathways in the brains of FTD sufferers

    • Research Objectives

    • Discovery and development of novel PET radiotracers targeting different phenotypes of neuroinflammation
    • Discovery of novel small molecules targeting pathological protein aggregation in neurodegenerative disease states