Woodruff Lab - Neuroinflammation
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.
- Arbore, Giuseppina, West, Erin E., Spolski, Rosanne, Robertson, Avril A. B., Klos, Andreas, Rheinheimer, Claudia, Dutow, Pavel, Woodruff, Trent M., Yu, Zu Xi, O'Neill, Luke A., Coll, Rebecca C., Sher, Alan, Leonard, Warren J., Koehl, Jorg, Monk, Pete, Cooper, Matthew A., Arno, Matthew, Afzali, Behdad, Lachmann, Helen J., Cope, Andrew P., Mayer-Barber, Katrin D. and Kemper, Claudia (2016) T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells. Science, 352 6292: 1424+-U95. doi:10.1126/science.aad1210
- Croker, Daniel E., Monk, Peter N., Halai, Reena, Kaeslin, Geraldine, Schofield, Zoe, Wu, Mike C. L., Clark, Richard J., Blaskovich, Mark A. T., Morikis, Dimitrios, Floudas, Christodoulos A., Cooper, Matthew and Woodruff, Trent M. (2016) Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling. Immunology and Cell Biology, 94 8: 787-795. doi:10.1038/icb.2016.43
- Nabizadeh, Jamileh A., Manthey, Helga D., Steyn, Frederik J., Chen, Weiyu, Widiapradja, Alexander, Akhir, Fazrena N. Md, Boyle, Glen M., Taylor, Stephen M., Woodruff, Trent M. and Rolfe, Barbara E. (2016) The complement C3a receptor contributes to melanoma tumorigenesis by inhibiting neutrophil and CD4+ T cell responses. Journal of Immunology, . doi:10.4049/jimmunol.1600210
- Mantovani, Susanna, Gordon, Richard, Li, Rui, Christie, Daniel C., Kumar, Vinod and Woodruff, Trent M. (2016) Motor deficits associated with Huntington's disease occur in the absence of striatal degeneration in BACHD transgenic mice. Human Molecular Genetics, 25 9: 1780-1791. doi:10.1093/hmg/ddw050
- Brennan, Faith H., Lee, John D., Ruitenberg, Marc J. and Woodruff, Trent M. (2016) Therapeutic targeting of complement to modify disease course and improve outcomes in neurological conditions. Seminars in Immunology, 28 3: 292-308. doi:10.1016/j.smim.2016.03.015
- Jeanes, Angela, Coulthard, Liam G., Mantovani, Susanna, Markham, Kathryn and Woodruff, Trent M. (2015) Co-ordinated expression of innate immune molecules during mouse neurulation. Molecular Immunology, 68 2: 253-260. doi:10.1016/j.molimm.2015.09.004
- Lee, Jia Y., Lee, John D., Phipps, Simon, Noakes, Peter G. and Woodruff, Trent M. (2015) Absence of toll-like receptor 4 (TLR4) extends survival in the hSOD1<sup>G93A</sup> mouse model of amyotrophic lateral sclerosis. Journal of Neuroinflammation, 12 1: . doi:10.1186/s12974-015-0310-z
- Coulthard, Liam G. and Woodruff, Trent M. (2015) Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. Journal of Immunology, 194 8: 3542-3548. doi:10.4049/jimmunol.1403068
- Hawksworth, Owen A., Coulthard, Liam G., Taylor, Stephen M., Wolvetang, Ernst J. and Woodruff, Trent M. (2014) Brief report: Complement C5a promotes human embryonic stem cell pluripotency in the absence of FGF2. Stem Cells, 32 12: 3278-3284. doi:10.1002/stem.1801
- Mantovani, S., Gordon, R., Macmaw, J. K., Plfluger, C. M., Henderson, R. D., Noakes, P. G., McCombe, P. A. and Woodruff, T. M. (2014) Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood. Journal of Neuroimmunology, 276 1-2: 213-218. doi:10.1016/j.jneuroim.2014.09.005
- Woodruff, Trent M., Lee, John D. and Noakes, Peter G. (2014) Role for terminal complement activation in amyotrophic lateral sclerosis disease progression. Proceeding of the National Academy of Sciences of the United States of America, 111 1: E3-E4. doi:10.1073/pnas.1321248111
- Wu, Mike C. L., Brennan, Faith H., Lynch, Jason P. L., Mantovani, Susanna, Phipps, Simon, Wetsel, Rick A., Ruitenberg, Marc J., Taylor, Stephen M.and Woodruff, Trent M. (2013) The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization. Proceedings of the National Academy of Sciences of the United States of America, 110 23: 9439-9444. doi:10.1073/pnas.1218815110
- Li, Rui, Coulthard, Liam G., Wu, M. C. L., Taylor, Stephen M. and Woodruff, Trent M. (2013) C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB Journal, 27 3: 855-864. doi:10.1096/fj.12-220509
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. Discovery and development of novel therapeutics targeting inflammatory diseases.