Woodruff Group - 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

Inflammation is increasingly implicated in the progression of neurodegenerative disease. The complement cascade and the inflammasomes are powerful innate immune systems that are key drivers of inflammation. Our laboratory is investigating the effects of complement and inflammasomes in several models of neurodegenerative disease, including motor neuron disease (MND or ALS), Huntington's disease, and Parkinson's disease, by using specific therapeutics developed by our team. We work closely with clinicians at Brisbane-based hospitals, who focus these conditions, to help translate our knowledge into the clinic for the benefit of patients. We are currently progressing one of our complement targeting drugs, PMX205, towards clinical trials for MND, in partnership with Alsonex Pharmaceuticals.

Complement anaphylatoxin agonists and antagonists as pharmacological modulators of immunopathology

We are collaborating with local and international medicinal chemists and immunologists to develop and test novel drugs which target the inflammatory process induced by innate immune activation. Our goal is to identify new clinical drugs targeting key effectors of complement activation, to treat a wide range of immunological diseases.

Role of the innate immune complement system in the development of the brain

We have discovered that components of the innate immune system are essential for aspects of neural development. Specific inhibition of the complement system leads to neurodevelopmental 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.

The Woodruff Group

 

Group Head

Staff

Postdocs

PhD students

For a full list of our laboratory publications and citations, please use one of the following links:

PubMed

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Scopus

Selected Research Articles

Lee JD, Liu N, Levin SC, Ottosson L, Andersson U, Harris HE, Woodruff TM. (2019). Therapeutic blockade of HMGB1 reduces early motor deficits, but not survival in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Journal of Neuroinflammation. 16(1):45.

Gordon R, Albornoz EA, Christie DC, Langley MR, Kumar V, Mantovani S, Robertson AAB, Butler MS, Rowe DB, O'Neill LA, Kanthasamy AG, Schroder K, Cooper MA, Woodruff TM. (2018). Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. Science Translational Medicine. 10(465). pii: eaah4066.

Coulthard LG, Hawksworth OA, Conroy J, Lee JD, Woodruff TM. (2018). Complement C3a receptor modulates embryonic neural progenitor cell proliferation and cognitive performance. Molecular Immunology. 101:176-181.

Coulthard LG, Hawksworth OA, Li R, Balachandran A, Lee JD, Sepehrband F, Kurniawan N, Jeanes A, Simmons DG, Wolvetang E, Woodruff TM. (2017). Complement C5aR1 Signaling Promotes Polarization and Proliferation of Embryonic Neural Progenitor Cells through PKCζ. Journal of Neuroscience. 37(22):5395-5407.

Gorelik A, Sapir T, Haffner-Krausz R, Olender T, Woodruff TM, Reiner O. (2017). Developmental activities of the complement pathway in migrating neurons. Nature Communications. 8:15096.

Lee JD, Kumar V, Fung JN, Ruitenberg MJ, Noakes PG, Woodruff TM. (2017). Pharmacological inhibition of complement C5a-C5a1 receptor signalling ameliorates disease pathology in the hSOD1G93A mouse model of amyotrophic lateral sclerosis. British Journal of Pharmacology. 174(8):689-699. 

Croker DE, Monk PN, Halai R, Kaeslin G, Schofield Z, Wu MC, Clark RJ, Blaskovich MA, Morikis D, Floudas CA, Cooper MA, Woodruff TM. (2016). Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling. Immunology & Cell Biology. 94(8):787-95.

Nabizadeh JA, Manthey HD, Steyn FJ, Chen W, Widiapradja A, Md Akhir FN, Boyle GM, Taylor SM, Woodruff TM*, Rolfe BE*. (2016). The Complement C3a Receptor Contributes to Melanoma Tumorigenesis by Inhibiting Neutrophil and CD4+ T Cell Responses. Journal of Immunology. 196(11):4783-92.

Mantovani S, Gordon R, Li R, Christie DC, Kumar V, Woodruff TM. (2016). Motor deficits associated with Huntington's disease occur in the absence of striatal degeneration in BACHD transgenic mice. Human Molecular Genetics. 25(9):1780-91.

Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, Woodruff TM, Ruitenberg MJ. (2015). The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury. Journal of Neuroscience. 35(16):6517-31.

Hawksworth OA, Coulthard LG, Taylor SM, Wolvetang EJ, Woodruff TM. (2014). Complement C5a promotes human embryonic stem cell pluripotency in the absence of FGF2. Stem Cells. 32(12):3278-84.

Mantovani S, Gordon R, Macmaw JK, Pfluger CM, Henderson RD, Noakes PG, McCombe PA, Woodruff TM. (2014). Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood. Journal of Neuroimmunology. 276(1-2):213-8.

Woodruff TM, Lee JD, Noakes PG. (2014). Role for terminal complement activation in amyotrophic lateral sclerosis disease progression. Proc Natl Acad Sci USA. 111(1):E3-4. 

Wu MC, Brennan FH, Lynch JP, Mantovani S, Phipps S, Wetsel RA, Ruitenberg MJ, Taylor SM, Woodruff TM. (2013). The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization. Proc Natl Acad Sci USA. 110(23):9439-44.

Selected Reviews

Coulthard LG, Hawksworth OA, Woodruff TM. (2018). Complement: The Emerging Architect of the Developing Brain. Trends in Neuroscience. 41(6):373-384.

Hawksworth OA, Coulthard LG, Mantovani S, Woodruff TM. (2018). Complement in stem cells and development. Seminars in Immunology. 37:74-84.

Tenner AJ, Stevens B, Woodruff TM. (2018). New tricks for an ancient system: Physiological and pathological roles of complement in the CNS. Molecular Immunology. (2018). 102:3-13. 

Hawksworth OA, Li XX, Coulthard LG, Wolvetang EJ, Woodruff TM. (2017). New concepts on the therapeutic control of complement anaphylatoxin receptors. Molecular Immunology. 89:36-43.

Brennan FH, Lee JD, Ruitenberg MJ, Woodruff TM. (2016). Therapeutic targeting of complement to modify disease course and improve outcomes in neurological conditions. Seminars in Immunology. 28(3):292-308.

Coulthard LG, Woodruff TM. (2015). Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. Journal of Immunology. 194(8):3542-8.

Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM. (2013). C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB Journal. 27(3):855-64.

Students interested in undertaking research higher degrees are encouraged to contact Associate Professor 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.

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