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 Leader

Postdocs

Research Assistants

PhD students

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

Selected Research Articles

Pandey S, Kumari P, Baidya M, Kise R, Cao Y, Dwivedi-Agnihotri H, Banerjee R, Li XX, Cui CS, Lee JD, Kawakami K, Maharana J, Ranjan A, Chaturvedi M, Jhingan GD, Laporte SA, Woodruff TM, Inoue A, Shukla AK. (2021) Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors. Molecular CellS1097-2765(21)00741-3. 

McGill RB, Steyn FJ, Ngo ST, Thorpe KA, Heggie S, Ruitenberg MJ, Henderson RD, McCombe PA, Woodruff TM. (2020) Monocytes and neutrophils are associated with clinical features in amyotrophic lateral sclerosis. Brain Communications. 14;2(1):fcaa013.

Li XX, Lee JD, Massey NL, Guan C, Robertson AAB, Clark RJ, Woodruff TM. (2020) Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function. Biochemical Pharmacology180:114156.

Li XX, Clark RJ, Woodruff TM. (2020) C5aR2 Activation Broadly Modulates the Signaling and Function of Primary Human Macrophages. Journal of Immunology15;205(4):1102-1112. 

Kumar V, Lee JD, Clark RJ, Noakes PG, Taylor SM, Woodruff TM. (2020) Preclinical Pharmacokinetics of Complement C5a Receptor Antagonists PMX53 and PMX205 in Mice. ACS Omega. 30;5(5):2345-2354. 

Deora V, Lee JD, Albornoz EA, McAlary L, Jagaraj CJ, Robertson AAB, Atkin JD, Cooper MA, Schroder K, Yerbury JJ, Gordon R, Woodruff TM. (2020) The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins. Glia. 68(2):407-421. 

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, 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. 

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.

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.

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

Woodruff TM, Shukla AK. (2020) The Complement C5a-C5aR1 GPCR Axis in COVID-19 Therapeutics. Trends in Immunology. 41(11):965-967. 

Lo MW, Woodruff TM. (2020) Complement: Bridging the innate and adaptive immune systems in sterile inflammation. Journal of Leukocyte Biology. 108(1):339-351. 

Lee JD, Coulthard LG, Woodruff TM. (2019) Complement dysregulation in the central nervous system during development and disease. Semin Immunol. 45:101340. 

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.

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.

Students interested in undertaking research higher degrees are encouraged to contact 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.
  3. Clinical studies to validate innate immune targets in neurological disease.
Join the Woodruff Group

We specialise in Parkinson’s disease, motor neuron disease; MND (amyotrophic lateral sclerosis; ALS) and neuroinflammation assays.

  • Capacity in preclinical drug testing (efficacy) indisease models, or target validation studies.
  • Range of state-of-the-art disease models accepted by funders and regulators as best-practice preclinical efficacy models.
  • An extensive range of both standardised and novelbehavioural and pathological analyses that can becustomised to suit individual requirements.
  • Can be coupled with pharmacodynamic and pharmacokinetic data from the same animal to maximisedata output and assay validation.
  • Successful record in completing industry contracts,with two drugs undergoing human clinical trialsafter successful testing in preclinical models.
  • Strong publication track record in preclinical neurodegenerative disease animal studies.
  • Offer opportunities for leverage funding throughnon-diluting grant funding.
  • Competitive rates for both fee-for-service or collaborative research projects.

In vivo models available

  • Neuroinflammation endotoxin model (peripheral orcentral induction)
  • Parkinson’s disease 6-hydroxydopamine (6-OHDA) model
  • Parkinson’s disease synuclein pre-formed fibril (PFF-Syn) model
  • Motor neuron disease SOD1G93A transgenic mouse model
  • Motor neuron disease TDP43-transgenic mouse models

In vitro/ex vivo models available

  • Primary human microglia neuroinflammation assays (derived from human blood)
  • Primary mouse microglia neuroinflammation assays (derived from mice CNS tissue)

Neurotransmitter and Metabolite Quantitation

  • We offer new methods to simultaneously measure a range of neurotransmitters, metabolites, vitamins, and short-chain fatty acids from any sample.
  • We utilise state-of-the-art LC-MS/MS methodology to provide full quantitation of analytes coupled with standard curves.
  • We have the ability to determine concentrations in a wide range of biological fluids or tissues from any animal or human species.
  • Analyses can be easily coupled with efficacy studies in neurodegenerative disease or psychiatry models to allow full quantitation of drug activities.

If you would like to make a tax deductible donation to neuroinflammation research, please contact med.advancement@uq.edu.au. Thank you for your support.

Find out more about our research environment and how to apply to do a short or long-term research project with us.