ONZM BMedSc MBChB PhD DSc FRSNZ
We have a broadly-based, multidisciplinary HRC Research Programme on "Neurodegeneration in the Human Brain - Mechanisms and Therapeutic Targets" in collaboration with Dr Henry Waldvogel and Dr Maurice Curtis (Department of Anatomy with Radiology), Professor Mike Dragunow and Dr Michelle Glass in the Department of Pharmacology, and Dr Lynette Tippett (School of Psychology) , which uses the human tissue stored in our Human Brain Bank and the molecular, cellular biological and imaging resources in the Centre for Brain Research. Research in the group is focused on the following major project areas:
- Molecular biological and anatomical studies on the chemical changes in the following major neurodegenerative diseases of the human brain – Huntington’s disease, Alzheimer’s disease, schizophrenia, Parkinson’s disease, epilepsy and Motor Neuron disease.
- Correlation of the clinical profile with the chemical anatomical pathology and genotype in Huntington’s disease, in order to determine whether variations in clinical symptomatology are reflected by variations in the chemical pathology and HD gene.
- The establishment of a transgenic sheep model of Huntington's disease in collaboration with Dr Russell Snell (School of Biological Sciences), Dr Simon Bawden (South Australian Research Development Institute), and Dr Marcy Macdonald and Professor Jim Gusella (Harvard University). This will be the first large animal model of a human brain disease in the world and will provide for studies on the pathogenesis and molecular mechanisms of Huntington's disease and, most importantly, will provide an animal model (whose brain is very similar to the human brain) for the development of novel therapeutic strategies for treating this tragic inherited human brain disease. This project has receceived major funding from The Freemasons of New Zealand.
- Molecular mechanisms and patterns of nerve cell death and repair in these neurodegenerative diseases focusing on the role of transcription factors and growth factors, and using in vitro cell culture models, and transgenic animal models.
- Investigations on the potential of various novel methods to treat neurodegenerative diseases including gene therapy techniques (decoy DNA, antisense DNA, peptide nucleic acids), and neurotrophins to prevent neuronal death in neurodegenerative diseases.
- In collaboration with Dr Bronwen Connor and Professor Mike Dragunow in Pharmacology, and Dr Maurice Curtis (University of Goteborg, Sweden) we are also studying neurogenesis in the human brain. The specific areas of interest are: (i) whether stem cells in the adult human brain and spinal cord have the ability to proliferate and form new neurons in response to brain injury and disease (Huntington's disease, Parkinson's Disease, Epilepsy, Alzheimer's disease, Motor Neuron Disease, Stroke); (ii) the pathways of neurogenesis in the human brain; (iii) the mechanisms involved in the induction of neurogenesis in the injured or diseased adult brain; and (iii) do stem cells have the potential to ‘repair’ the injured or diseased adult brain and spinal cord.
Some recent publications:
- Curtis MA, Kam M, Nannmark U, Zetterstrom M, Wikkelso C, Holtas S, van Roon-Mom WMC, Bjork-Eriksson T, Nordborg C, Dragunow M, Faull RLM, Eriksson PS (2007). Human Neuroblasts Migrate to the Olfactory Bulb via a Lateral Ventricular Extension. Science, 315, 1243-1249.
- Tippett LJ, Waldvogel HJ, Thomas SJ, Hogg VM, van Roon-Mom W, Synek BJ, Graybiel AM, Faull RLM (2007). Striosomes and mood dysfunction in Huntington’s disease. Brain, 130, 206-221.
- Waldvogel HJ, Baer K, Allen KL, Rees MI, Faull RLM (2007). Glycine receptors in the striatum, globus pallidus and substantia nigra of the human brain: an immunohistochemical study. J. Comp. Neurol., 502, 1012-1029.
- Narayan PJ, Gibbons HM, Mee E, Faull RLM, Dragunow M (2007). High throughput quantification of cells with complex morphologies in mixed cultures. Journal of Neuroscience Methods, 164, 339-349.
- Curtis MA, Faull RLM, Eriksson PS (2007). The Effect of Neurodegenerative Diseases on the Subventricular Zone. Nature Reviews Neuroscience, 8, 712-723.
- Waldvogel HJ, Curtis MA, Baer K, Rees MI, Faull RLM (2006). Immunohistochemical staining of post-morten adult human brain sections. Nature Protocols, 1, 2719-2732.
- Hodges A, Strand AD, Aragaki AK, Sengstag T, Hughes G, Elliston LA, Hartog C, Goldstein DR, Régulier E, Zala D, Sick B, Thu D, Hollingsworth ZR, Collin F, Synek B, Holmans PA, Aebischer P, Ferrante RJ, Young AB, Delorenzi M, Déglon N, Kooperberg C, Augood SJ, Faull RLM, Olson JM, Jones L, Luthi-Carter R (2006). Regional and cellular gene expression changes in human Huntington’s disease brain. Human Molecular Genetics, 15, 965-977.
- Curtis MA, Penney EB, Pearson AG, van Roon-Mom WMC, Butterworth NJ, Dragunow M, Connor B, Faull RLM (2003). Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proc. Natl. Acad. Sci. USA, 100, 9023-9027.