Dr Trent Woodruff

Position

ARC Future Fellow

Senior Lecturer in Pharmacology

Qualifications and Awards

PhD in Pharmacology, University of Queensland (2000-2003)
NHMRC Biomedical Career Development Award (2008-2012)
QLD Premiers Award for Health and Medical Research (2008)
Denis Wade Johnson and Johnson New Investigator Award (2008)
NHMRC Career Development Award (2008 - 2012)
UQ Early Career Researcher Award (2009)
The 2011 Edgeworth David Medal

Associations

International Complement Society (2004 -present)
Australian Neuroscience Society
The Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists
The Australian Society for Medical Research
Huntington's Disease Association, QLD

Contact Details

Location Room 516, Skerman Building (No 65), St Lucia Campus,
Mail School of Biomedical Sciences,
The University of Queensland,
BNE, QUEENSLAND 4072
Telephone +61 3365 2924
Facsimile +61 3365 1766
Email t.woodruff@uq.edu.au

Biography

 
Dr Woodruff is an ARC Future Fellow and Senior Lecturer conducting research into the innate immune system in the brain, in both health and disease, spanning embryonic neurodevelopment to adult neurodegeneration.
 
Dr Woodruff’s specific research revolves around the Complement System, and the role its major activation fragments, C3a and C5a, play in neurobiology. A focus of his work has been the chronic neurodegenerative diseases amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson's disease as well as the acute injuries of ischemic stroke and spinal cord injury. Using a series of potent and orally active C5a receptor antagonists developed at the University of Queensland, Dr Woodruff has shown the therapeutic potential of targeting complement-mediated neuroinflammation to reduce neuronal cell death in these neurodegenerative diseases.
 
In 2010, Dr Woodruff started his own group and independent laboratory in the School of Biomedical Sciences, UQ. His team has recently shown that in addition to their roles in neurodegeneration, C5a and C3a also play essential roles in neuronal development during embryogenesis, revealing the widespread physiological and pathological roles of this evolutionarily ancient immune system.
 

Research Interests

Therapeutic Modulation of Inflammation in Neurodegenerative Disease
 
The complement factors C3a and C5a are a potent inflammatory molecules. Inflammation is increasingly implicated in the progression of neurodegenerative disease. Our laboratory is investigating the effects of C3a and C5a in several models of neurodegenerative disease, including Huntington's disease, motor neuron disease, Parkinson's disease, and Alzheimer's disease, by using a specific C3a and C5a receptor therapeutics, and novel transgenic mice and tools developed by our group.

   

Complement anaphylatoxin agonists and antagonists as pharmacological modulators of immunopathology

 

Complement anaphylatoxin agonists and antagonists as pharmacological modulators of immunopathology
We are collaborating with local and International groups to develop and test novel drugs which target the inflammatory process induced by Complement system activation. We are also working closely with clinicians at the Royal Brisbane & Women's Hospital, Brisbane, who focus on neurodegenerative and inflammatory diseases, to help translate our knowledge into the clinic, for the benefit of patients.

Role of the innate immune complement system in the development of the brain
We have found for the first time that components of the innate immune system are essential for aspects of neural development. Specific inhibition of the complement system, combined with folate deficiency leads to drastic neural tube defects in mice.

We are exploring the roles this system plays in the development of the brain, which will provide clues to what happens when things go wrong - and potential ways to combat this.

Selected Publications

Pavlovski D, Thundyil J, Monk PN, Wetsel RA, Taylor SM, Woodruff TM. (2012). Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis. FASEB Journal. Epub May 31. [Impact Factor: 7.2]

Bellows-Peterson ML, Fung HK, Floudas CA, Kieslich CA, Zhang L, Morikis D, Wareham KJ, Monk PN, Hawksworth OA, Woodruff TM. (2012). De novo Peptide design with C3a receptor agonist and antagonist activities: theoretical predictions and experimental validation. Journal of Medicinal Chemistry. 55:4159-68. [Impact Factor: 5.2]

Lee JD, Lee JY, Taylor SM, Noakes PG, Woodruff TM. Innate immunity in ALS. In Amyotrophic Lateral Sclerosis. ISBN 979-953-307-199-1.

Coulthard LG, Costello J, Robinson B, Shiels IA, Taylor SM, Woodruff TM. (2011). Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced arthritis. Arthritis Research & Therapy 13: R42. [Impact Factor: 4.8]
 
Woodruff TM, Thundyil J, Tang SC, Taylor SM, Arumugam TV. (2011). Pathophysiology, Treatment, and Animal and Cellular Models of Human Ischemic Stroke. Molecular Neurodegeneration 2: 15. [Impact Factor: 5.4]
 
Woodruff TM, Nandakumar KS, Tedesco F. (2011). Inhibiting the C5-C5a receptor axis. Molecular Immunology 48: 1631-43. [Impact Factor: 3.0]
 
Beck KD, Nguyen HX, Galvan MD, Salazar DL, Woodruff TM, Anderson AJ. (2010). Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain 133: 433-47. [Impact Factor: 10.1]
 
Woodruff TM, Ager RR, Tenner AJ, Noakes PG, Taylor SM. The role of the complement system and the activation fragment C5a in the central nervous system. (2010). Neuromolecular Medicine 12: 179-92. [Impact Factor: 4.7]
 
Crane JW, Baiquni G, Sullivan R, Lee JD, Sah P, Taylor SM, Noakes PG, Woodruff TM. (2009). The C5a anaphylatoxin receptor CD88 is expressed in presynaptic terminals of hippocampal mossy fibres. Journal of Neuroinflammation 6: 34. [Impact Factor: 5.8]
 
Proctor LM, Moore T, Monk PN, Sanderson SD, Taylor SM, Woodruff TM. (2009) Complement Factors C3a and C5a and C-terminal peptide analogues have distinct haemodynamic effects in the rat. International Immunopharmacology. 9: 800-6. [Impact Factor: 2.5]
 
Fonseca MI, Rahasson AR, Shu-Hui C, Yazan O, Sanderson SD, LaFerla FM, Taylor SM, Woodruff TM, Tenner AJ. Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer’s disease. Journal of Immunology. 183: 1375-83. [Impact Factor: 5.9]
 
Woodruff TM, Denny KJ, Crane JD, Atkin JD, Taylor SM, Noakes PN. (2008). The Complement Factor C5a Contributes to Pathology in a Rat Model of Amyotrophic Lateral Sclerosis. Journal of Immunology. 181: 8727-8734. [Impact Factor:5.9]
 
Woodruff TM, Crane JW, Proctor LM, Buller KM, Shek AB, de Vos K, Pollitt S, Williams HM, Shiels IA, Monk PN, Taylor SM. (2006). Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration. FASEB Journal. 20: 1407-17. [Impact Factor: 7.2]
 
Woodruff TM, Pollitt S, Proctor LM, Stocks SZ, Manthey HD, Williams HM, Mahadevan IB, Shiels IA, Taylor SM. (2005). Increased potency of a novel complement factor 5a receptor antagonist in a rat model of inflammatory bowel disease. Journal of Pharmacology and Experimental Therapeutics. 314: 811-817. [Impact Factor: 4.1]
 
Woodruff TM, Arumugam TV, Shiels IA, Reid RC, Fairlie DP, Taylor SM. (2003). A potent human C5a receptor antagonist protects against disease pathology in a rat model of inflammatory bowel disease. Journal of Immunology. 171: 5514-20. [Impact Factor: 5.9].
 
Woodruff TM, Strachan AJ, Dryburgh N, Shiels IA, Reid RC, Fairlie DP, Taylor SM. (2002). Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Arthritis and Rheumatism. 46: 2476-85. [Impact Factor: 8.6].
 
Woodruff TM, Strachan AJ, Sanderson SD, Monk PN, Wong AK, Fairlie DP, Taylor SM. Species dependence for binding of small molecule agonist and antagonists to the C5a receptor on polymorphonuclear leukocytes. Inflammation. 2001 Jun;25(3):171-7. [Impact Factor: 1.9].

Grants

Grants as Lead Investigator (CIA):

Fellowship: National Health and Medical Research Council of Australia: Career Development Award (2008 - 2012). The Role of the Complement System in Neurodegeneration and the Therapeutic Potential of Complement Inhibition $370,000.
 
Donation: Australian Huntington’s Disease Association; PhD Scholarship (2009-2013) $87,500.
 
UQ Collaborative Industry and Engagement Fund (2011 - 2013). Therapeutic modulation of the innate immune complement system as a new and adjunct therapy to treat a wide variety of cancers $84,984.
 
National Health and Medical Research Council of Australia: Project Grant (2011 - 2013). Therapeutic Targeting of Complement C5a Receptors in Huntington’s Disease $452,319.
 
National Health and Medical Research Council of Australia: Project Grant (2012 - 2014). Contribution of Complement C5a to Neuronal Cell Death during Ischemic Stroke $439,925.
 
Other Successful Grants as Chief Investigator:
 
ARC Linkage Grant (2008 - 2010) $221,180 [CIB]
 
ARC Linkage Grant (2008 - 2012) $270,000 [CID]
 
NHMRC Project Grant (2009 - 2013) $1,021,750 [CIB]
 
NHMRC Project Grant (2009 - 2011) $516,250 [CIE]
 
National Heart Foundation of Australia – Grant in Aid (2010) $129,000 [CIB]
 
Charles & Shirley Graham Motor Neuron Disease Grant (2011 - 2012) $80,000 [CIB]
 

PhD and Honours Projects

Students interested in undertaking research higher degrees are encouraged to contact Dr Woodruff. The following projects are available:

1. Therapeutic potential of targeting innate immune molecules in neurodegenerative disease.
2. Complement pathway expression and biochemistry in the neonatal and adult murine and human brain.
3. Developmental role of innate immune pathways in the mouse and human brain.
4. Therapeutic potential of targeting C3a receptors in treating acute neutrophil-mediated disease.
5. Discovery and development of novel therapeutics targeting inflammatory diseases.

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