School of Medical Sciences

Neural repair and neurogenesis

Principal investigator

Research interests

Our research programme focuses on the development of novel therapeutic strategies to repair or protect the brain from injury or disease. In particular, we are interested in the use of stem cell therapy and gene delivery techniques. We are investigating whether brain injury or disease, such as stroke or Parkinson's disease, stimulates stem cells in the adult brain to form new replacement neurons in an attempt by the adult brain to "repair" itself.

Using a combination of molecular, pharmacological and physiological/anatomical approaches, we are investigating the function of stem cells in the adult brain and the molecular and extracellular signaling factors that direct stem cells to migrate to areas of cell loss and turn into new neurons.

We are also interested in whether mental health disorders such as depression and schizophrenia are associated with an altered ability for stem cells to make new brain cells. Demonstration that stem cells are involved in the development of depression and schizophrenia will provide new targets for drug development.

Cell transplantation offers a viable treatment strategy for patients with neurological disorders by providing new cells to replace those lost through disease or injury. We are undertaking studies to examine whether transplantation of stem cells has the potential to provide replacement neurons for patients suffering from neurological disorders such as Parkinson's disease or Huntington's disease.

In particular, we are examining techniques by which to enhance the survival and generation of transplanted cells in the injured or disease brain. In addition, we are undertaking studies to determine the potential therapeutic use of gene delivery to provide long-term targeted expression of specific neuroprotective factors to the Huntington's disease brain. We are examining whether increased expression of neuroprotective factors via gene delivery techniques can prevent the progressive loss of cells and motor function impairment observed in Huntington's disease. The combined results of this research programme will provide the tools to allow us to develop and assess the potential use of novel therapeutic strategies for the treatment of neurological diseases.

Research fellows

Dr Christof Maucksch
Dr Renee Gordon

Graduate students

Jane Evans
Kathryn Jones
Amelia van Slooten
Rosemary Knobloch
Siu Kwan Tang

Research staff

Erin Firmin
Yvonne Sun

Current research projects

CHDI: AAV-BDNF Gene Therapy for the Treatment of Huntington’s Disease (Connor)
MPPT: Connexin 43 Mimetic Peptide Therapy for the Treatment of Stroke. (Connor, McGregor, Nicholson and Green)
NARSAD: Stress, Neurosteroids and Depression. (Connor)
Neurological Foundation: Stress, Neurosteroids and Depression (Connor)
Neurological Foundation: Regulating macrophage and microglial effector functions during neuroinflammation. (LaFlamme and Connor)
Lotteries Nealth: Neuronal and Cognitive Enhancement by Secreted Amyloid Precursor Protein-alpha. (Abraham, Connor and Tate)
Neurological Foundation: The Role of Chemokines in Directing Progenitor Cell Migration Following Brain Injury (Connor and Gordon)
Neurological Foundation: Characterisation of Neurogenesis in the Huntington’s Disease Rat Transgenic Model. (McGregor and Connor)
HRC Program Grant: Neurogenesis and Neurodegenerative Disorders of the Human Brain (Faull, Dragunow, Connor, Glass and Waldvogel)

International collaborations

Howard Florey Institute, Melbourne: Prof. Malcolm Horne
University of Melbourne, Melbourne: Dr Mirella Dottori
University of Southern California, California, USA: Dr Martin Pera
Northwestern University, Chicago, USA: Dr Martha Bohn
GSF - Institute of Stem Cell Research, Germany: Prof Magdalena Gotz
Depaul University, Chicago, IL, USA: AP Dorothy Kozlowski

National collaborations

University of Otago: Prof Cliff Abraham and Prof Warren Tate
Victoria University: AP Anne La Flamme

Facilities / technologies

Molecular Biology: qPCR, RT-PCR, cloning techniques, plasmid and vector construction Protein biochemistry.
Gene transfer: in vitro and in vivo Stem cell technology; development of techniques to isolate and culture of adult rodent and human neural stem cells.
Cell culture techniques: primary and engineered cell lines. Cell transplantation techniques.
Small animal surgery: generation of animal models of neurological disease. Behavioural and motor function analysis
Organotypic slice culture techniques.
Immunocytochemistry and histology: fluorescent double/triple labeling and confocal analysis.  

Research publications

Journal articles (last 10 years)

B. Connor and K. S. Jones. 2011. Proneural transcription factors Dlx2 and Pax6 are altered in adult SVZ neural precursor cells following striatal cell loss. Molecular and Cellular Neuroscience. In Press.
B. Connor, R.J. Gordon, K.S. Jones and C. Maucksch. 2011. Deviating From the Well Travelled Path: Precursor Cell Migration in the Pathological Adult Mammalian Brain. Journal of Cellular Biochemistry. In Press
E. M. Vazey and B. Connor. 2010. Differential Fate and Functional Outcome of Lithium Chloride Primed Adult Neural Progenitor Cell Transplants in a Rat Model of Huntington's Disease. Stem Cell Research and Therapy. 19.
E. M. Vazey, M. Dottori, P. Jamshidi, D. Tomas, M. F. Pera, M. Horne and B. Connor. 2010 Comparison of Transplant Efficiency Between Spontaneously-Derived and Noggin-Primed Human Embryonic Stem Cell Neural Precursors in the Quinolinic Acid Rat Model of Huntington’s Disease. Cell Transplantation; 19; 1055-1062.
S. M.F. Jamieson, J. Subramaniam, J.J. Liu, N.N. Jong, V. Ip, B. Connor and M.J. McKeage. 2009. Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue. Molecular Pain. 5:66.
R.J. Gordon, A.L. McGregor and B. Connor. 2009. Chemokines direct neural progenitor cell migration following striatal cell loss. Molecular and Cellular Neuroscience. . 41; 219-232
E.M. Vazey and B. Connor. 2009. In Vitro Priming to Direct Neuronal Fate in Adult Neural Progenitor Cells. Experimental Neurology. In Press.
M. Kam, M. A. Curtis, S.R. McGlashan, B. Connor, U. Nannmark, R.L.M. Faull. 2009. The cellular composition and morphological organization of the rostral migratory stream in the adult human brain. Journal of Chemical Neuroanatomy. In Press.
Y. W. J. Liu, M. A. Curtis, H. M. Gibbons, E. W. Mee, P. S. Bergin, H. H. Teoh, B. Connor, M. Dragunowand R. L. M. Faull. 2008. Doublecortin expression in the normal and epileptic adult human brain. European Journal of Neuroscience. 28; 2254-2265
A.P. Kells and B. Connor. 2008. AAV-mediated Expression of Bcl-xL or XIAP Fails to Induce Neuronal Resistance Against Quinolinic Acid-induced Striatal Lesioning. Neuroscience Letters. 436; 326-360.
A.P. Kells, R.A. Henry and B. Connor. 2008. AAV-BDNF Mediated Attenuation of Quinolinic Acid-Induced Neuropathology and Motor Function Impairment. Gene Therapy. 15; 966-977.
P.M. Aponso, R.L.M. Faull and B. Connor. 2008. Increased Progenitor Cell Proliferation and Astrogenesis in the Partial Progressive 6-OHDA Model of Parkinson's Disease. Neuroscience. 151: 1142-1153
S.M.F. Jamieson, J.J. Liu, B. Connor, M. Dragunow, and M.J. McKeage. 2007. Nucleolar Enlargement, Nuclear Eccentricity and Altered Cell-Body Immunostaining Characteristics of Large-Sized Sensory Neurons Following Treatment of Rats with Paclitaxel. Neurotoxicology. 28; 1092-1098
K. Chen, S.M. Hughes, and B. Connor. 2007. Neural Progenitor Cells Derived From The Adult Rat Subventricular Zone: Characterization And Transplantation. Cell Transplantation. 16: 799-811.
K. Chen, R. A. Henry, S. M. Hughes and B. Connor. 2007.Creating a Neurogenic Environment: The Role of BDNF and FGF2. Molecular and Cellular Neuroscience. 36: 108-120
R.A. Henry, S.M. Hughes and B. Connor. 2007. AAV-Mediated Delivery of BDNF Augments Neurogenesis in the Normal and Quinolinic Acid Lesioned Adult Rat Brain. European Journal of Neuroscience.25; 3512-3525
Y.W.J.Liu, E.W. Mee, P. Bergin, H.H. Teoh, B. Connor, M. Dragunow, and R.L.M. Faull. 2007. Adult Neurogenesis in Mesial Temporal Lobe Epilepsy: A Review of Recent Animal and Human Studies. Current Pharmaceutical Biotechnology. 8: 187-194
R. J. Gordon, A.S. Tattersfield, E.M. Vazey, A.P. Kells, A.L. McGregor, S.M. Hughes and B. Connor. 2007. Temporal Profile of Subventricular Zone Progenitor Cell Migration Following Quinolinic Acid Induced Striatal Cell Loss. Neuroscience. 146: 1704-1718
A.P. Kells, R.A Henry, S.M. Hughes and B. Connor. 2007.Verification of Functional AAV-mediated Neurotrophic and Anti-Apoptotic Factor Expression. Journal of Neuroscience Methods. 161: 291-300.
E.M. Vazey, K. Chen, S.M. Hughes., and B. Connor. 2006.Transplanted Adult Neural Progenitor Cells Survive, Differentiate and Reduce Motor Function Impairment in a Rodent Model of Huntington’s Disease. Experimental Neurology 199: 384-396.
S. Jamieson, J. Liu, B. Connor and M. McKeage. 2005. Oxaliplatin causes selective atrophy of a subpopulation of dorsal root ganglion neurons without inducing cell loss. Cancer Chemotherapy and Pharmacology 56: 391-399.
M.A. Curtis, E.B. Penney, J. Pearson, M. Dragunow, B. Connor and R.L.M. Faull. 2005. The distribution of progenitor cells in the subependymal layer of the lateral ventricle in the normal and Huntington’s disease human brain. Neuroscience 132: 777-788.
D.A. Kozlowski, E.A. Miljan, E.G. Bremer, C.G. Harrod, C. Gerin, B. Connor, D. George, B. Larson, & M.C. Bohn. 2004. Quantitative analyses of GFR a -1 and GFR a -2 mRNAs and tyrosine hydroxylase protein in the nigrostriatal system reveal bilateral compensatory changes following unilateral 6-OHDA lesions in the rat. Brain Research 1016; 170-181.
A.S. Tattersfield, R.J. Croon, Y.W. Liu, A. Kells, R.L.M. Faull and B. Connor. 2004. Neurogenesis in the Striatum of the Quinolinic Acid Lesion Model of Huntington’s Disease. Neuroscience 127; 319-332.
A.P. Kells, D.M. Fong, M, Dragunow, M.J. During, D. Young and B. Connor. 2004. AAV-mediated gene delivery of BDNF or GDNF is neuroprotective in a model of Huntington’s disease. Molecular Therapy 9; 682-688.
M.A. Curtis, B. Connor, R.L.M. Faull. 2003. Neurogenesis in the diseased adult human brain: new therapeutic strategies for neurodegenerative diseases. Cell Cycle 2; 428-430.
M.A. Curtis, E.B. Penney, A.G. Pearson, W.M.C. Van Roon-Mom, N.J. Butterworth, M. Dragunow, B. Connor *, and R.L.M. Faull. 2003. Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proceedings of the National Academy of Science 100; 9023-9027. * Joint PI B.
Connor, W.M.C. van Roon-Mom, M.A. Curtis, M. Dragunow and R.L.M. Faull. 2001. Stem cells and neurodegenerative disease. New Zealand Medical Journal 114; 477 - 479.
B. Connor . 2001. Adenoviral vector-mediated delivery of glial cell line-derived neurotrophic factor provides neuroprotection in the aged parkinsonian rat. Clinical and Experimental Pharmacology and Physiology 28; 896-901.
B. Connor, D.A. Kozlowski, J.R. Unnerstall, J.D. Elsworth, T. Schallert, J.L. Tillerson, B.L. Davidson, and M.C. Bohn. 2001. Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects dopaminergic terminals from degeneration. Experimental Neurology 169; 83-95.
D.A. Kozlowski, B. Connor, J.L. Tillerson, T. Schallert and M.C. Bohn. 2000. Delivery of a GDNF gene into the substantia nigra after a progressive 6-OHDA lesion maintains functional nigrostriatal connections. Experimental Neurology 166; 1-15.
M.C. Bohn, D.A. Kozlowski and B. Connor. 2000. Glial cell line-derived neurotrophic factor (GDNF) as a defensive molecule for neurodegenerative disease: A tribute of Antonia Vernadakis’s studies on neuronal-glial interactions. International Journal for Developmental Neuroscience 18: 679-684. B.

Sections in books

B. Connor. 2010. Adult Neural Progenitor Cells and Cell Replacement Therapy for Huntington’s Disease. In: Stem Cell Biology and Regenerative Medicine; From Molecular Embryology to Tissue Engineering. Eds: Appasani, K; Appasani, R. Springer Press, NY.
M.A. Curtis, A.S. Tattersfield, M. Kam, E.B. Penney, R.J. Croon, Y.W. Liu, M. Dragunow, R.L.M. Faull and B. Connor. 2005. Neurogenesis in the basal ganglia in Huntington’s disease in the human brain and in an animal model. The 8th International Basal Ganglia Conference. Kluwer Academic/Plenum Publishers. 233 Spring St, New York, NY 10013, USA.
M.C. Bohn, B. Connor, D.A. Kozlowski and M.H. Mohajeri. 2000. Gene transfer for neuroprotection in animal models of Parkinson's disease and amyotrophic lateral sclerosis. In: Neural Transplantation in Neurodegenerative Disease: Current status and new directions. John Wiley and Sons, LTD, Chichester, Novartis Foundation Symposium 231: 70-93.
B. Connor and M. Dragunow. 1999. The role of neuronal growth factors in the Alzheimer’s disease brain. In: Research and Practise in Alzheimer’s Disease. Eds. B. Vellas and L.J. Fitten, Springer Publishing Company, NY. Volume 2: 83-88.
Housley, G.D., Connor, B. and Raybould, N.P. 1995. Purinergic modulation of outer hair cell electromotility. In: "Active Hearing", Å. Flock, D. Ottoson and M. Ulfendahl (Eds.). Elsevier, Oxford. pp. 219 – 236.