Crack laboratory: Neuropharmacology
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Dr Peter Crack PhD is head of the Neuropharmacology Research Group in the Department of Pharmacology and Therapeutics at the University of Melbourne, Melbourne, Australia. His group’s research interest focuses on the mechanisms of cell death seen in neural injury and the effect of oxidative stress and neuroinflammation in contributing to neural cell death, in both acute and chronic neuropathologies. In investigating these mechanisms there is a focus on traumatic brain injury (TBI) as a representative of acute neuropathology and Alzheimer’s disease (AD) and Parkinson’s disease (PD) as representatives of chronic neuropathologies. The group seeks to find similarities in disease propagation and progression and is interested in the role of the immune system and its components, specifically type-1 IFN signalling, in both the central and peripheral contribution to the outcome in TBI, AD and PD.
In focusing on the mechanisms of cell death seen in neural injury – both acute and chronic, we have developed in vitro and in vivo models which include primary neuronal, astrocyte and microglial cultures, in vivo models of stroke and traumatic brain injury and have established mouse models of Alzhiemers and Parkinsons disease, which include behavioural readouts. These in vitro and in vivo models are complemented by protein chemistry, molecular biology, immunohistochemistry and cellular imaging.
Dr Juliet Taylor, Senior Research Fellow
Mr Zachery Moore, PhD Student
Mr Amar Abdullah, PhD Student
Ms Linh Lam, PhD Student
Ms Kaelyn Tan, Masters Student
Ms Samantha Matta, Masters Student
Assistant Professor Saul Villeda, UCSF
Professor Iain Campbell, University of Sydney
Professor Roberto Cappai, University of Melbourne
Professor Norman Saunders, University of Melbourne
Dr Bridgette Semple, University of Melbourne
Associate Professor Ashley Mansell, Hudson Institute
Professor Terry O'Brien, Monash University
Professor Paul Hertzog, Hudson Institute
Associate Professor Ross Vlahos, RMIT
Associate Professor Elisa HIll, RMIT
Associate Professor Tony White, QIMR
Professor Rob Medcalf, Monash University
Professor Hongxing Lei, Beijing Institute of Genomics
Associate Professor Nigel Jones, University of Melbourne
Associate Professor Trent Woodruff, University of Queensland
Associate Professor David Finkelstein, Florey Neurosciences Institute
Associate Professor Rohan Walker, University of Newcastle
Professor Jurgen Bernhagen, University of Munich
Professor John Forsythe, Monash University
Professor Mibel Aguilar, Monash University
- Karve IP, Zhang Z, Habgood M, Frugier T, Sashindranath M, Ek CJ, Chappaz S, Kile BT, Wright D, Wang H, Johnston L, Daglas M, Ates RC, Medcalf RL, Taylor JM, Crack PJ.
Ablation of type-1 IFN signalling in hematopoietic cells confers protection following traumatic brain injury. eNeuro 2016 Feb 18; 3(1).
This research is the culmination of a wide-ranging collaborative study that places type-1 interferon signalling as an important signalling pathway in the progression of neural injury after brain trauma. This work highlights the type-1 interferon receptor as a viable drug target in the treatment of traumatic brain injury.
- Main BS, Zhang M, Brody KM, Ayton S, Frugier T, Steer D, Finkelstein D, Crack PJ, Taylor JM.
Type-1 interferons contribute to the neuroinflammatory response and disease progression of the MPTP mouse model of Parkinson's disease. Glia 2016 Sep; 64(9): 1590-604. PMID 27404846.
This paper is the first report of the type-1 interferon system being involved in the progression the PD and highlights IFN signalling as a novel therapeutic target the the disease.
- Minter MR, Moore Z, Zhang M, Brody KM, Jones NC, Shultz SR, Taylor JM, Crack PJ.
Deletion of the type-1 interferon receptor in APPSWE/PS1ΔE9 mice preserves cognitive function and alters glial phenotype. Acta Neuropathologica Communications 2016 Jul 11; 4(1):72. PMID 27400725.
This most recent paper crossed the APP/PS1 mouse with the IFNAR1-/- to generate the APP/PS1/IFNAR1-/- which slowed the cognitive decline of the APP/PS1 background. This paper highlights the expertise of Associate Professor Crack in characterising newly generated animal models.
- Taylor JM, Minter MR, Newman AG, Zhang M, Adlard PA, Crack PJ.
Type-1 interferon signaling mediates neuro-inflammatory events in models of Alzheimer's disease. Neurobiology of Aging 2014 May; 35(5): 1012-23.
This publication is the first of its kind reporting the role of the type-1 interferon system in regulating the neuroinflammation that is seen in Alzheimer’s disease. This paper lays the grounding for the hypothesis that type-1 IFN driven neuroinflammation is detrimental in chronic neuropathologies.
- Minter MR, Main BS, Brody KB, Zhang M, Taylor JM, Crack PJ.
Soluble Amyloid Triggers A Myeloid Differentiation Factor 88 And Interferon Regulatory Factor 7 Dependent Neuronal Type-1 Interferon Response In Vitro. Journal of Neuroinflammation 2015 Apr 12; 12: 71.
This publication further explores the mechanisms of A-beta neurotoxicity and identifies an IRF-7 dependent mechanism that may be involved in the pathology of Alzheimer's disease.
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