Stem Cells for Drug Discovery and Regenerative Therapy
Our group utilize advance in cell biology to generate stem cells from patients to use for drug discovery. In particular, test efficiency and response to existing anti-seizure medication, screen and identify compounds with anti-seizure properties which could potentially lead to the development of new anti-epileptic medications.
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Our impact
The Homer Hack update
Our neuroscience researchers are testing drugs on brain cells in a dish, to help us understand neurological disorders caused by variants to the Homer family of genes" moving us towards personalised treatments.
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Stem Cell theme group. (L - R ) Front row - Dr Ana Antonic-Baker, Mr Hailin Zhu, Miss Elena Vianca, Professor Patrick Kwan, Middle row – Dr Hugh Simpson, Dr Muhammad Shahid Javaid, Miss Xiaojie Song, Back row – Miss Afaf Altalhi, Mr Daniel Sandvik (Absent – Dr Ben Rollo, Dr Jinchao Gu, Miss Eliza Moore, Mr Joshua Nicholls)
Project Leads - Dr Ana Antonic-Baker and Prof Terence O'Brien This study aims to investigate whether stem cells can be used as vehicles to deliver - neuropeptide (neuropeptide Y) - an amino-acid known to suppress seizures in drug-resistant epilepsy. This study will provide new insights into how epilepsy develops, and form the basis for the development of novel disease-modifying treatment or strategies.
Project Leads - Dr Ben Rollo and Prof Patrick Kwan Failure of modern anti-seizure medications (ASMs) to reduce the prevalence of drug-resistant epilepsy has been attributed to over-reliance on rodent models of acute seizures in drug development as they do not adequately recapitulate the mechanisms of human epilepsy. We developed a novel in vitro ASM screening platform made up of singular layers of neurons produced from human induced pluripotent stem cells. The platform replicates the pharmacological effects of ASMs on neural activity measured by a multi-electrode array. We will use our stem cell platform to fast-track the development of a new class of ASMs that modulate adenosine A1 receptor (through our medicinal chemistry collaborators at the Faculty of Pharmacy, Monash University and published in Nature 2021). These compounds enhance the effect of adenosine (which surges in response to seizure activity in the brain) to stop the seizure. After optimisation for safety, metabolic stability and brain penetration, the lead compounds will progress to animal testing in our Neuroscience Laboratory.
Project Lead - Dr Shahid Javaid The stem cell laboratory is investigating new treatments for a class of patients that do not respond to mainstream anti-seizure medications (ASMs). Our laboratory has created patient-derived neurons. This project will utilise patient-derived iPSC-derived neuronal cultures with functional multi-electrode array (MEA) analysis to screen an FDA-approved drug library and identify drugs that can be readily repurposed into “n of 1” clinical trials of patients with Homer1 mutations. This project also has the potential to provide effective “personalised” medicine treatment for patients with brain diseases due to Homer1 mutations and provide new insights into the role of Homer family in neurobiological normal function that may open up new treatment options for brain disease.
Patient-Specific Disease Models for Investigating Homer1 Gene Mutations: Implications for Neurological and Cardiovascular Conditions
The primary aim of this project is to gain a deeper understanding of and develop effective treatments for neurological and cardiovascular disorders linked to abnormal calcium signalling due to mutations in the Homer1 gene. To accurately reflect the pathophysiology of affected individuals, the project stresses the importance of using patient-specific neuronal disease models, with emphasis on astrocytes, another cell type of central nervous system, which is critical for synaptic plasticity and calcium signalling. Additionally, given that Homer1 has a potential role in modulating calcium signalling in the heart, it is crucial to investigate its impact on cardiac function and pathology. This project will use patient-derived stem cell lines to generate neuronal and cardiac cellular models to comprehensively explore the pathophysiological spectrum of Homer1 variants and to develop effective treatments for associated conditions.
Extracellular Vesicles from Epilepsy Patient-Derived Neurons Promote Epileptogenesis and Drug Resistance: Uncovering New Drug Targets
Extracellular Vesicles (EVs) are nano-sized membrane-bound vesicles, encompassing exosomes and microvesicles, secreted by cells into the extracellular environment. EVs play a crucial role in cell-to-cell communication within the central nervous system (CNS), performing functions ranging from the removal of unwanted biomolecules to facilitating the spread of pathogenic proteins linked to neurodegenerative diseases. This project focuses on the role of EVs in intracellular pathogenicity and emphasizes the importance of utilizing autologous astrocytes for CNS disease modelling. The project outcomes aim to identify potential new drug targets, offering valuable insights for therapeutic development. In collaboration with The Australian Centre for Blood Disease (ACBD) at the Alfred Centre, this research employs advanced techniques, including Mass Spectrometry, Nano Tracking Analysis, as well as Cell Culture and Molecular Biology methodologies.
