Professor Trevor Kilpatrick

Professor Trevor Kilpatrick

MB BS (Melb) PhD (Melb) FRACP

Senior Principal Research Fellow
Group Leader, Multiple Sclerosis Group
Laboratory Head, Multiple Sclerosis Laboratory

Trevor Kilpatrick is a Senior Principal Research Fellow at the Howard Florey Institute and Director of the Centre for Neuroscience, The University of Melbourne. He trained in clinical neurology at the Royal Melbourne Hospital and then completed a PhD in developmental neuroscience at the Walter and Eliza Hall Institute of Medical Research. He then undertook post-doctoral studies in the molecular neurobiology laboratory of The Salk Institute for Biological Studies and at the Institute of Neurology, London. He returned to the Royal Melbourne Hospital as a consultant neurologist and to The Walter and Eliza Hall Institute as a faculty member in 1995, since which time he has established a multidisciplinary research program as a clinician-scientist focusing on the neurobiology of demyelinating diseases, in particular multiple sclerosis. In 2003, he joined the Howard Florey Institute and the University of Melbourne as Professor of Neurology. Currently, he heads a scientific group that encompasses three laboratories in the Howard Florey Institute and the Centre for Neuroscience at the University of Melbourne, as well as a clinical research facility at the Royal Melbourne Hospital. In total, the group has 26 researchers and students undertaking work in this arena.

Contact Details

Email:

trevor.kilpatrick@florey.edu.au

Phone:

+61 (0)3 8344 1804

Fax:

+61 (0)3 9349 5917

Research Interests

Multiple Sclerosis (MS) is traditionally viewed as an example of an autoimmune disease in which inflammatory cells target the brain to induce demyelination. However, in recent years, it has become increasingly apparent that MS is an example of inflammatory neurodegeneration in which the nature of the response of the central nervous system to the inflammatory insult is a determinant of disease severity. Whilst anti-inflammatory therapies have been developed that are partially effective in ameliorating MS, no therapy has, as yet, been developed that either targets the neurodegenerative component of the
disease or which enhances the capacity for nervous system repair. Professor Kilpatrick’s research is attempting to develop such therapies by concentrating on three areas of research:

In addition, via collaborative interaction with Dr Simon Murray, he is investigating how neurotrophin signalling influences myelination. In collaboration with Dr Justin Rubio and others he is also attempting to identify the genetic and environmental factors that both predispose to and influence the phenotype of MS.

Over the past decade, it has been established that stem cell populations reside within discrete regions of the adult mammalian brain. By studying the molecular response of one of these regions (the subventricular zone) to a demyelinative insult Professor Kilpatrick’s group has identified candidate genes that are potentially important in mounting a regenerative response. One important candidate is the transforming growth factor family and we are currently exploring the influence of this series of factors on precursor cells. Several other candidates are also actively being pursued in collaboration with the biotechnology company, Schering AG.

Professor Kilpatrick’s second area of interest is to develop strategies to promote the survival of the oligodendrocyte, the cell responsible for producing myelin and which is targeted in the context of MS. The Kilpatrick group has a strong background in this area, having previously identified that Leukemia Inhibitory Factor (LIF) receptor signalling is a key component of the oligodendrocyte’s response to a demyelinative insult in vivo, that exogenous LIF provides therapeutic benefit in two independent animal models of MS and that the molecule, SOCS3, is a key negative regulator of the LIF-mediated beneficial effect. Our most recent work has clarified how LIF potentially provides this beneficial effect. Gene expression profiling analyses have identified that LIF induces a neurosecretory phenotype in oligodendrocytes and that amongst other effects it induces the secretin of galanin, a neuropeptide that in other injury models has been identified to have a neuroprotective effect. This work raises exciting possibilities concerning novel therapeutic candidates that might act downstream of LIF.

Another emerging area of interest for Professor Kilpatrick relates to the development of a platform to facilitate our capacity to translate animal-based discoveries to the clinic. To facilitate this, Professor Kilpatrick recognises that we need to develop surrogate markers of key elements of the neuropathology of MS. He is, therefore, in collaboration with A/Prof Gary Egan’s Neuroimaging Group at the Howard Florey Institute developing magnetic resonance imaging (MRI) to analyse the influence of neuroprotective and regenerative therapies in a mouse model of MS. This work has identified that diffusion weighted imaging is a sensitive indicator of key elements of pathology, in particular of axonal degeneration. The results of this work are now being applied to human MRI to enhance our capacity to test the efficacy of therapeutic candidates in the clinic.

Laboratory Techniques

Selected Publications

Emery B, Cate HS, Marriott M, Merson T, Binder MD, Snell C, Soo PY, Murray S, Croker B, Zhang JG, Alexander WS, Cooper H, Butzkueven H, Kilpatrick TJ.
Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination.
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7859-64.

Butzkueven H, Emery B, Cipriani T, Marriott MP, Kilpatrick TJ.
Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss.
Glia. 2006 May;53(7):696-703.

Emery B, Merson TD, Snell C, Young KM, Ernst M, Kilpatrick TJ.
SOCS3 negatively regulates LIF signaling in neural precursor cells.
Mol Cell Neurosci. 2006 Apr;31(4):739-47.

Emery B, Butzkueven H, Snell C, Binder M, Kilpatrick TJ.
Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor.
Neuroscience. 2006;137(2):463-72.

Kilpatrick TJ, Butzkueven H, Emery B, Marriott M, Taylor BV, Tubridy N.
Neuroglial responses to CNS injury: prospects for novel therapeutics.
Expert Rev Neurother. 2004 Sep;4(5):869-78.

Ponsonby AL, van der Mei I, Dwyer T, Blizzard L, Taylor B, Kemp A, Simmons R, Kilpatrick T.
Exposure to infant siblings during early life and risk of multiple sclerosis.
JAMA. 2005 Jan 26;293(4):463-9.

Pitman M, Emery B, Binder M, Wang S, Butzkueven H, Kilpatrick TJ.
LIF receptor signaling modulates neural stem cell renewal.
Mol Cell Neurosci. 2004 Nov;27(3):255-66.

Petratos S, Gonzales MF, Azari MF, Marriott M, Minichiello RA, Shipham KA, Profyris C, Nicolaou A, Boyle K, Cheema SS, Kilpatrick TJ.
Expression of the low-affinity neurotrophin receptor, p75(NTR), is upregulated by oligodendroglial progenitors adjacent to the subventricular zone in response to demyelination.
Glia. 2004 Oct;48(1):64-75.

Rubio JP, Bahlo M, Tubridy N, Stankovich J, Burfoot R, Butzkueven H, Chapman C, Johnson L, Marriott M, Mraz G, Tait B, Wilkinson C, Taylor B, Speed TP, Foote SJ, Kilpatrick TJ.
Extended haplotype analysis in the HLA complex reveals an increased frequency of the HFE-C282Y mutation in individuals with multiple sclerosis.
Hum Genet. 2004 May;114(6):573-80.

Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study.
BMJ. 2003 Aug 9;327(7410):316.

Butzkueven H, Zhang JG, Soilu-Hanninen M, Hochrein H, Chionh F, Shipham KA, Emery B, Turnley AM, Petratos S, Ernst M, Bartlett PF, Kilpatrick TJ.
LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival.
Nat Med. 2002 Jun;8(6):613-9.

Rubio JP, Bahlo M, Butzkueven H, van Der Mei IA, Sale MM, Dickinson JL, Groom P, Johnson LJ, Simmons RD, Tait B, Varney M, Taylor B, Dwyer T, Williamson R, Gough NM, Kilpatrick TJ, Speed TP, Foote SJ.
Genetic dissection of the human leukocyte antigen region by use of haplotypes of Tasmanians with multiple sclerosis.
Am J Hum Genet. 2002 May;70(5):1125-37.

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