Head of Laboratory

Dr Trent Woodruff

Location

Room 514, Skerman Building

Staff

  • Dr Richard Gordon (post-doc)
  • Dr Susanna Mantovani (post-doc)
  • Dr Angela Jeanes (post-doc)

Students

  • Dale Pavlovski (PhD student)
  • Mike Wu (PhD student)
  • John Lee (PhD student)
  • Peppermint Lee (PhD student)
  • Liam Coulthard (PhD student)
  • Owen Hawksworth (PhD student)
  • Fazrena Akhir (PhD student)
  • Vinod Kumar (PhD student)
  • Rui Li (Masters student)

Research

Our group conducts research into innate immune system in the brain, in both health and disease, spanning embryonic neurodevelopment to adult neurodegeneration.

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 specific C3a and C5a receptor therapeutics, and novel transgenic mice and tools developed by our group. Our goal is to develop new clinical drugs to treat these diseases.

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 innate immune 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.

Recent publications

  1. 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. 26: 3680-90. [Impact Factor: 7.2]
  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]
  3. Lee JD, Lee JY, Taylor SM, Noakes PG, Woodruff TM. Innate immunity in ALS. In Amyotrophic Lateral Sclerosis. ISBN 979-953-307-199-1.
  4. Woodruff TM, Nandakumar KS, Tedesco F. (2011). Inhibiting the C5-C5a receptor axis. Molecular Immunology 48: 1631-43. [Impact Factor: 3.0]
  5. 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]
  6. 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]
  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]
  8. 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 Alzheimers disease. Journal of Immunology. 183: 1375-83. [Impact Factor: 5.9]
  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]

Student 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.

Research support

Australian Research Council Future Fellowship: (2012 - 2015). Investigating the Role of the Innate Immune Complement System in the Abnormal Development of the Central Nervous System $714,528.

National Health and Medical Research Council of Australia: Project Grant (2009 - 2013). Inflammation of the Womb During Pregnancy and Reproductive Consequences $967,750.

National Health and Medical Research Council of Australia: Project Grant (2011 - 2013). Therapeutic Targeting of Complement C5a Receptors in Huntingtons 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.

Links

International Complement Society