Neurodegenerative diseases cause neurons to deteriorate and die. A result of this is the abnormal build-up of proteins such as tau or TPD-43. Evidence from our group suggests that inflammation is dysregulated in these diseases, playing a detrimental role in the disease progression. It is our goal to identify disease-causing inflammation and treat these diseases as early as possible.
About our research
Emerging evidence from our group has shown that inflammation is dysregulated and escalates from the earliest stages of neurodegeneration; indicating that inflammation actively modulates disease development.
Our group seeks to elucidate the molecular events underlying disease causing inflammatory responses in neurodegenerative disease. This involves investigating immune-mediated cellular and molecular changes which arise as result of the abnormal build-up of protein (i.e. tau or TDP-43).
We bring together expertise in immunology, neuroscience and computational biology, using techniques such as molecular biology, advanced imaging, preclinical mouse models, human induced pluripotent stem cell technology and translational research.
Identifying the disease-causing inflammatory pathways will enable us to better understand the causes of neurodegenerative disease and allow us to work towards earlier diagnosis and targeted therapies.
Hear Alan talk about our research: https://www.youtube.com/watch?v=ShidgAlsvLE
- Neurodegenerative diseases
- Motor neurone disease
- Frontotemporal dementia
- Human iPSC technology
- Spatial transcriptomics
- Western blot, qPCR
- Preclinical mouse models
‘We aspire to map the cause(s) of neurodegeneration through the lens of immunology towards novel therapeutic strategies for ALS-FTD. Our work is ‘dynamic’, ‘collaborative’ and ‘inspiring’. We are a cohesive bunch and love to explore the truth behind the microscope.’
Research and technical staff
- Brooke McDonald
- Pawat Laohamonthonkul
- Pippa Priguer
- Aggie Hansen
- Yu, C.-H., Davidson, S., Harapas, C.R., Hilton, J.B., Mlodzianoski, M.J., Laohamonthonkul, P., Louis, C., Low, R.R.J., Moecking, J., De Nardo, D., Balka, K.R., Calleja, D.J., Moghaddas, F., Ni, E., McLean, C.A., Samson, A.L., Tyebji, S., Tonkin, C.J., Bye, C.R. and Turner, B.J. (2020). TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS. Cell, 183(3), pp.636-649.e18. doi:https://doi.org/10.1016/j.cell.2020.09.020.
- McDonald, B.K., Pawat Laohamonthonkul and Yu, C.-H. (2023). Stray self-nucleic acids: the emerging drivers of neurodegeneration. Trends in Cell Biology. doi:https://doi.org/10.1016/j.tcb.2023.02.006.
- Davidson, S., Yu, C.-H., Steiner, A., Ebstein, F., Baker, P.J., Jarur-Chamy, V., Hrovat Schaale, K., Laohamonthonkul, P., Kong, K., Calleja, D.J., Harapas, C.R., Balka, K.R., Mitchell, J., Jackson, J.T., Geoghegan, N.D., Moghaddas, F., Rogers, K.L., Mayer-Barber, K.D., De Jesus, A.A. and De Nardo, D. (2022). Protein kinase R is an innate immune sensor of proteotoxic stress via accumulation of cytoplasmic IL-24. Science Immunology, 7(68). doi:https://doi.org/10.1126/sciimmunol.abi6763.
- Eitan, C., Siany, A., Barkan, E., Olender, T., van Eijk, K.R., Moisse, M., Farhan, S.M.K., Danino, Y.M., Yanowski, E., Marmor-Kollet, H., Rivkin, N., Yacovzada, N.S., Hung, S.-T., Cooper-Knock, J., Yu, C.-H., Louis, C., Masters, S.L., Kenna, K.P., van der Spek, R.A.A. and Sproviero, W. (2022). Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3′UTR protect against ALS. Nature Neuroscience, 25(4), pp.433–445. doi:https://doi.org/10.1038/s41593-022-01040-6.
- Tye, H., Yu, C.-H., Simms, L.A., Marcel, Man Soo Kim, Zakrzewski, M., Jocelyn Sietsma Penington, Harapas, C.R., Souza-Fonseca-Guimaraes, F., Wockner, L.F., Preaudet, A., Mielke, L.A., Wilcox, S., Ogura, Y., Corr, S.C., Komal Kanojia, Kouremenos, K.A., De, D.P., McConville, M.J. and Flavell, R.A. (2018). NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease. Nature Communications, 9(1). doi:https://doi.org/10.1038/s41467-018-06125-0.