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
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.