Neurogenesis and Neural Transplantation

 

Lachlan Thompson BSc (Melb) PhD (Monash)

NHMRC CDA Fellow

Florey Faculty

Research Focus

Our laboratory is focused on developing regenerative therapies for brain and spinal cord repair. Like many neurobiologists in this field, we share the view that success in this area will be closely aligned with a deeper understanding of the complex processes that underlie brain development. We are particularly interested in the molecular mechanisms that underlie neurogenesis as well as neurite outgrowth and connectivity in the developing brain. Our goal is to adapt key concepts in this area to the development of stem cell-based therapies for brain repair and a central focus is the generation of midbrain dopamine neurons from pluripotent stem cells for use in transplantation-based procedures for Parkinson’s disease. We are also working on similar approaches for other neurological conditions including stroke, motor neuron disease and Huntington’s disease. In addition to transplantation-based strategies we are also exploring other novel avenues for brain repair including the use of viral vectors to deliver trophic factors that can protect neurons from injury or even promote ‘self-repair’ from the brain’s own stem cells.

 

 

                                                                                                                                                          

Current Projects

  • Optimising neural transplantation for Parkinson’s disease.
  • Understanding forebrain Neurogenesis in response to injury.
  • Development of stem cell therapies for brain and spinal cord repair.
  • Gene-based approaches for facilitating ‘self-repair’ of the injured brain.

Research Team

Dr. Chris Bye (postdoctoral research associate).

Ms. Mong Tien (research assistant).

Mr. Jordan Wright (Postgraduate student).


 

 

Technical Expertise

                Embryonic microdissection

                Flow cytometry (incl. FACS)

                Stereotaxic surgery

                Neural Transplantation

                Disease modeling and behavioural phenotyping in rodents

                 Immunochemistry

                Is situ hybridization histochemistry

                Genetic manipulation in vitro and in vivo using plasmid and viral vectors

 

Funding

NHMRC CDA Fellowship (2011 – 2014)

NHMRC Project grant scheme

Motor Neuron Disease Research Institute


Collaborators

National

Dr. Clare Parish, Florey Neuroscience Institute.

Dr. Mirella Dottori and Dr. Mark Denham, University of Melbourne.

Prof. Martin Pera, University of Melbourne/Florey Neuroscience Institute.

Prof. Glenda Halliday, Neuroscience Research Australia.

 

International

Dr. Deniz Kirik, Lund University, Sweden.

Dr. Jesper Jorgensen, NsGene A/S Ballerup, Denmark.

 


Selected Publications

Denham M, Thompson LH, Leung J, Pebay A, Bjorklund A, Dottori M.

Gli1 is an Inducing Factor in Generating Floorplate Progenitor Cells from Human Embryonic Stem Cells. Stem Cells. 2010 28(10):1805-15.

Grealish S, Jonsson M, Li M, Kirik D, Bjorklund A, Thompson LH.

Midbrain Dopamine Neuronal Subtype Composition in Intra-striatal Grafts of Ventral Mesencephalon is an Important Determinant of Functional Efficacy. Brain. 2010 Feb;133(2):482-95.

Thompson LH, Grealish S, Kirik D, Bjorklund A.

Reconstruction of the Nigro-striatal Dopamine Pathway in the Adult Mouse Brain. Eur J Neurosci. 2009 Aug; 30(4):625-38.

Jonsson ME, Ono Y, Bjorklund A,Thompson LH.

Identification of Transplantable Dopamine Neuron Precursors at Different Stages of Midbrain Neurogenesis. Exp Neurol. 2009 Sep; 219(1):341-54.

Jørgensen JR, Thompson L, Fjord-Larsen L, Krabbe C, Torp M, Kalkkinen N, Hansen C, Wahlberg L.

Characterization of Meteorin-An Evolutionary Conserved Neurotrophic Factor. J Mol Neurosci. 2009 Sep; 39(1-2):104-16.

Friling S, Andersson E, Thompson LH, Jönsson ME, Hebsgaard JB, Nanou E, Alekseenko Z, Marklund U, Kjellander S, Volakakis N, Hovatta O, El Manira A, Björklund A, Perlmann T, Ericson J.

Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells. PNAS. 2009 106(18):7613-8

Thompson LH, Kirik D, Bjorklund A.

Non-dopaminergic neurons in ventral mesencephalic transplants make widespread axonal connections in the host brain. Exp Neurol. 2008 Sep;213(1):220-8.

Irvin DK, Kirik D, Bjorklund A,Thompson LH.

In vivo gene delivery to proliferating cells in the striatum generated in response to a 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway. Neurobiol Dis. 2008 Jun;30(3):343-52.

Thompson L*, Andersson E*, Jensen J, Barraud P, Guillemot F, Parmar M, Bjorklund A.

Neurogenin2identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon. Exp Neurol. 2006 Mar;198(1):183-98.

Thompson L, Barraud P, Andersson E, Kirik D, Bjorklund A.

Identification of dopaminergic neurons of nigral and VTA subtypes in grafts of foetal ventral mesencephalon based on cell morphology, protein expression and efferent projections. J Neurosci. 2005 Jul 6;25(27):6467-77.

Back to Research Groups