Associate Professor Adam Walker
Ross Maclean Fellow - GL
Queensland Brain Institute
Dr Adam Walker: Neurodegeneration pathobiology
The Walker lab uses biochemistry and imaging techniques to study neuronal cell culture and genetically modified mouse models of MND and FTD, alongside analysis of human brain and spinal cord samples, to investigate the involvement of TDP-43 in disease. Importantly, Dr Walker previously characterised new TDP-43 mice that develop both pathology and motor phenotypes reminiscent of human disease, which are a vital new tool for both investigations of disease mechanisms and pre-clinical testing of therapeutics.
Researcher biography
Dr Adam Walker received his BSc(Hons) in Biochemistry from the University of Tasmania, and PhD in Neuroscience from the Florey Institute of Neuroscience and Mental Health at the University of Melbourne, focused on understanding the molecular mechanisms of motor neuron disease (MND). He undertook a postdoctoral fellowship with Professor Virginia Lee at the Center for Neurodegenerative Disease Research, University of Pennsylvania (2011-2015), developing new transgenic TDP-43 mouse models of disease. Dr Walker was previously an NHMRC CJ Martin Overseas Biomedical Research Fellow and was awarded an NHMRC RD Wright Career Development Fellowship (2018-2022), to continue his research on neurodegenerative diseases. His research has been supported by fellowships and project grants from the Australian National Health and Medical Research Council, the Australian National Foundation for Medical Research and Innovation, Dementia Australia, Motor Neuron Disease Research Institute of Australia, MonSTaR Foundation and the Cure for MND Foundation.
Book Chapters
Wu, Jemma X., Pascovici, Dana, Wu, Yunqi, Walker, Adam K. and Mirzaei, Mehdi (2023). Application of WGCNA and PloGO2 in the analysis of complex proteomic data. Statistical analysis of proteomic data: methods and tools. (pp. 375-390) edited by Thomas Burger. New York, NY, United States: Humana Press. doi: 10.1007/978-1-0716-1967-4_17
Walker, A. K., Turner, B. J. and Atkin, J. D. (2009). Endoplasmic reticulum stress and protein misfolding in amyotrophic lateral sclerosis. Protein Misfolding Disorders: A Trip into the ER. (pp. 56-76) edited by K. Walker, A., J. Turner, B. and D. Atkin, J.. Bentham Science Publishers Ltd.. doi: 10.2174/978160805013010901010056
Journal Articles
San Gil, Rebecca, Pascovici, Dana, Venturato, Juliana, Brown-Wright, Heledd, Mehta, Prachi, Madrid San Martin, Lidia, Wu, Jemma, Luan, Wei, Chui, Yi Kit, Bademosi, Adekunle T., Swaminathan, Shilpa, Naidoo, Serey, Berning, Britt A., Wright, Amanda L., Keating, Sean S., Curtis, Maurice A., Faull, Richard L. M., Lee, John D., Ngo, Shyuan T., Lee, Albert, Morsch, Marco, Chung, Roger S., Scotter, Emma, Lisowski, Leszek, Mirzaei, Mehdi and Walker, Adam K. (2024). A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration. Nature Communications, 15 (1) 1508, 1508. doi: 10.1038/s41467-024-45646-9
Jacobs, Matisse T., San Gil, Rebecca and Walker, Adam K. (2023). UndERACting ion channels in neurodegeneration. Trends in Neurosciences, 47 (2), 87-89. doi: 10.1016/j.tins.2023.11.002
Swanson, Molly E.V., Mrkela, Miran, Murray, Helen C., Cao, Maize C., Turner, Clinton, Curtis, Maurice A., Faull, Richard L.M., Walker, Adam K. and Scotter, Emma L. (2023). Microglial CD68 and L-ferritin upregulation in response to phosphorylated-TDP-43 pathology in the amyotrophic lateral sclerosis brain. Acta Neuropathologica Communications, 11 (1) 69, 1-22. doi: 10.1186/s40478-023-01561-6
Luan, Wei, Wright, Amanda L., Brown-Wright, Heledd, Le, Sheng, San Gil, Rebecca, Madrid San Martin, Lidia, Ling, Karen, Jafar-Nejad, Paymaan, Rigo, Frank and Walker, Adam K. (2023). Early activation of cellular stress and death pathways caused by cytoplasmic TDP-43 in the rNLS8 mouse model of ALS and FTD. Molecular Psychiatry, 28 (6), 2445-2461. doi: 10.1038/s41380-023-02036-9
Keating, Sean S., Bademosi, Adekunle T., San Gil, Rebecca and Walker, Adam K. (2023). Aggregation-prone TDP-43 sequesters and drives pathological transitions of free nuclear TDP-43. Cellular and Molecular Life Sciences, 80 (4) 95, 1-23. doi: 10.1007/s00018-023-04739-2
Bademosi, Adekunle T. and Walker, Adam K. (2022). Cryptic inclusions UNCover losses driving neurodegeneration. Trends in Genetics, 38 (9), 889-891. doi: 10.1016/j.tig.2022.06.004
Keating, Sean S., San Gil, Rebecca, Swanson, Molly E.V., Scotter, Emma L. and Walker, Adam K. (2022). TDP-43 pathology: from noxious assembly to therapeutic removal. Progress in Neurobiology, 211 102229, 102229. doi: 10.1016/j.pneurobio.2022.102229
Zamani, Akram, Walker, Adam K., Rollo, Ben, Ayers, Katie L., Farah, Raysha, O’Brien, Terence J. and Wright, David K. (2022). Impaired glymphatic function in the early stages of disease in a TDP-43 mouse model of amyotrophic lateral sclerosis. Translational Neurodegeneration, 11 (1) 17, 1-11. doi: 10.1186/s40035-022-00291-4
Tsitkanou, Stavroula, Della Gatta, Paul A., Abbott, Gavin, Wallace, Marita A., Lindsay, Angus, Gerlinger-Romero, Frederico, Walker, Adam K., Foletta, Victoria C. and Russell, Aaron P. (2022). miR-23a suppression accelerates functional decline in the rNLS8 mouse model of TDP-43 proteinopathy. Neurobiology of Disease, 162 105559, 105559. doi: 10.1016/j.nbd.2021.105559
Zamani, Akram, Walker, Adam K., Rollo, Ben, Ayers, Katie L., Farah, Raysha, O'Brien, Terence J. and Wright, David K. (2022). Early and progressive dysfunction revealed by in vivo neurite imaging in the rNLS8 TDP-43 mouse model of ALS. NeuroImage: Clinical, 34 103016, 103016. doi: 10.1016/j.nicl.2022.103016
Wright, Amanda L., Della Gatta, Paul A., Le, Sheng, Berning, Britt A., Mehta, Prachi, Jacobs, Kelly R., Gul, Hossai, San Gil, Rebecca, Hedl, Thomas J., Riddell, Winonah R., Watson, Owen, Keating, Sean S., Venturato, Juliana, Chung, Roger S., Atkin, Julie D., Lee, Albert, Shi, Bingyang, Blizzard, Catherine A., Morsch, Marco and Walker, Adam K. (2021). Riluzole does not ameliorate disease caused by cytoplasmic TDP‐43 in a mouse model of amyotrophic lateral sclerosis. European Journal of Neuroscience, 54 (6) ejn.15422, 6237-6255. doi: 10.1111/ejn.15422
Dyer, Marcus S., Reale, Laura A., Lewis, Katherine E., Walker, Adam K., Dickson, Tracey C., Woodhouse, Adele and Blizzard, Catherine A. (2021). Mislocalisation of TDP-43 to the cytoplasm causes cortical hyperexcitability and reduced excitatory neurotransmission in the motor cortex. Journal of Neurochemistry, 157 (4), 1300-1315. doi: 10.1111/jnc.15214
Cheng, Flora, De Luca, Alana, Hogan, Alison L., Rayner, Stephanie L., Davidson, Jennilee M., Watchon, Maxinne, Stevens, Claire H., Muñoz, Sonia Sanz, Ooi, Lezanne, Yerbury, Justin J., Don, Emily K., Fifita, Jennifer A., Villalva, Maria D., Suddull, Hannah, Chapman, Tyler R., Hedl, Thomas J., Walker, Adam K., Yang, Shu, Morsch, Marco, Shi, Bingyang, Blair, Ian P., Laird, Angela S., Chung, Roger S. and Lee, Albert (2021). Unbiased label-free quantitative proteomics of cells expressing Amyotrophic Lateral Sclerosis (ALS) mutations in CCNF reveals activation of the apoptosis pathway: a workflow to screen pathogenic gene mutations. Frontiers in Molecular Neuroscience, 14 627740, 1-18. doi: 10.3389/fnmol.2021.627740
Konopka, Anna, Whelan, Donna R., Jamali, Md Shafi, Perri, Emma, Shahheydari, Hamideh, Toth, Reka P., Parakh, Sonam, Robinson, Tina, Cheong, Alison, Mehta, Prachi, Vidal, Marta, Ragagnin, Audrey M G, Khizhnyak, Ivan, Jagaraj, Cyril J., Galper, Jasmin, Grima, Natalie, Deva, Anand, Shadfar, Sina, Nicholson, Garth A., Yang, Shu, Cutts, Suzanne M., Horejsi, Zuzana, Bell, Toby D M, Walker, Adam K., Blair, Ian P. and Atkin, Julie D. (2020). Impaired NHEJ repair in amyotrophic lateral sclerosis is associated with TDP-43 mutations. Molecular neurodegeneration, 15 (1) 51, 51. doi: 10.1186/s13024-020-00386-4
Gil, R. San, Cox, D., McAlary, L., Berg, T., Walker, A. K., Yerbury, J. J., Ooi, L. and Ecroyd, H. (2020). Neurodegenerative disease-associated protein aggregates are poor inducers of the heat shock response in neuronal cells. Journal of Cell Science, 133 (15), 1-15. doi: 10.1242/jcs.243709
Wu, Jemma X., Pascovici, Dana, Wu, Yunqi, Walker, Adam K. and Mirzaei, Mehdi (2020). Workflow for rapidly extracting biological insights from complex, multicondition proteomics experiments with WGCNA and PloGO2. Journal of Proteome Research, 19 (7), 2898-2906. doi: 10.1021/acs.jproteome.0c00198
Perri, Emma R., Parakh, Sonam, Vidal, Marta, Mehta, Prachi, Ma, Yi, Walker, Adam K. and Atkin, Julie D. (2020). Correction: The cysteine (Cys) residues Cys-6 and Cys-111 in mutant superoxide dismutase 1 (SOD1) A4V are required for induction of endoplasmic reticulum stress in amyotrophic lateral sclerosis. Journal of Molecular Neuroscience, 70 (9), 1369-1369. doi: 10.1007/s12031-020-01617-5
Perri, Emma R., Parakh, Sonam, Vidal, Marta, Mehta, Prachi, Ma, Yi, Walker, Adam K. and Atkin, Julie D. (2020). The cysteine (Cys) residues Cys-6 and Cys-111 in mutant superoxide dismutase 1 (SOD1) A4V are required for induction of endoplasmic reticulum stress in amyotrophic lateral sclerosis. Journal of Molecular Neuroscience, 70 (9), 1357-1368. doi: 10.1007/s12031-020-01551-6
Hedl, Thomas J., San Gil, Rebecca, Cheng, Flora, Rayner, Stephanie L., Davidson, Jennilee M., De Luca, Alana, Villalva, Maria D., Ecroyd, Heath, Walker, Adam K. and Lee, Albert (2019). Proteomics approaches for biomarker and drug target discovery in ALS and FTD. Frontiers in Neuroscience, 13 (JUN) 548, 548. doi: 10.3389/fnins.2019.00548
Wang, Guoying, Fu, Libing, Walker, Adam, Chen, Xianfeng, Lovejoy, David B., Hao, Mingcong, Lee, Albert, Chung, Roger, Rizos, Helen, Irvine, Mal, Zheng, Meng, Liu, Xiuhua, Lu, Yiqing and Shi, Bingyang (2019). Label-free fluorescent poly(amidoamine) dendrimer for traceable and controlled drug delivery. Biomacromolecules, 20 (5), 2148-2158. doi: 10.1021/acs.biomac.9b00494
Berning, Britt A. and Walker, Adam K. (2019). The Pathobiology of TDP-43 C-Terminal Fragments in ALS and FTLD. Frontiers in Neuroscience, 13 (APR) 335, 335. doi: 10.3389/fnins.2019.00335
McCann, Emily P., Fifita, Jennifer A., Grima, Natalie, Galper, Jasmin, Mehta, Prachi, Freckleton, Sarah E., Zhang, Katharine Y., Henden, Lyndal, Hogan, Alison L., Chan Moi Fat, Sandrine, Wu, Sharlynn S.L., Jagaraj, Cyril J., Berning, Britt A., Williams, Kelly Louise, Twine, Natalie A., Bauer, Denis, Piguet, Olivier, Hodges, John, Kwok, John B.J., Halliday, Glenda M., Kiernan, Matthew C., Atkin, Julie, Rowe, Dominic B., Nicholson, Garth A., Walker, Adam K., Blair, Ian P. and Yang, Shu (2019). Genetic and immunopathological analysis of CHCHD10 in Australian amyotrophic lateral sclerosis and frontotemporal dementia and transgenic TDP-43 mice. Journal of Neurology, Neurosurgery and Psychiatry, 91 (2), 162-2019. doi: 10.1136/jnnp-2019-321790
Wu, Yantong, Li, Shasha, Liu, Jinjin, Liu, Xiping, Ruan, Weimin, Lu, Jengwei, Liu, Yong, Lawson, Tom, Shimoni, Olga, Lovejoy, David B., Walker, Adam K., Cong, Yue and Shi, Bingyang (2018). Stilbenes from Veratrum maackii Regel protect against ethanol-induced DNA damage in mouse cerebellum and cerebral cortex. ACS Chemical Neuroscience, 9 (7), 1616-1624. doi: 10.1021/acschemneuro.8b00006
Parakh, Sonam, Jagaraj, Cyril J., Vidal, Marta, Ragagnin, Audrey M. G., Perri, Emma R., Konopka, Anna, Toth, Reka P., Galper, Jasmin, Blair, Ian P., Thomas, Colleen J., Walker, Adam K., Yang, Shu, Spencer, Damian M. and Atkin, Julie D. (2018). ERp57 is protective against mutant SOD1-induced cellular pathology in amyotrophic lateral sclerosis. Human Molecular Genetics, 27 (8), 1311-1331. doi: 10.1093/hmg/ddy041
Lee, Albert, Rayner, Stephanie L., De Luca, Alana, Gwee, Serene S. L., Morsch, Marco, Sundaramoorthy, Vinod, Shahheydari, Hamideh, Ragagnin, Audrey, Shi, Bingyang, Yang, Shu, Williams, Kelly L., Don, Emily K., Walker, Adam K., Zhang, Katharine Y., Yerbury, Justin J., Cole, Nicholas J., Atkin, Julie D., Blair, Ian P., Molloy, Mark P. and Chung, Roger S. (2017). Casein kinase II phosphorylation of cyclin F at serine 621 regulates the Lys48-ubiquitylation E3 ligase activity of the SCF(cyclin F) complex. Open Biology, 7 (10) 170058, 170058. doi: 10.1098/rsob.170058
Sundaramoorthy, Vinod, Walker, Adam K., Tan, Vanessa, Fifita, Jennifer A., Mccann, Emily P., Williams, Kelly L., Blair, Ian P., Guillemin, Gilles J., Farg, Manal A. and Atkin, Julie D. (2017). Erratum: Defects in optineurin- and myosin VI-mediated cellular trafficking in amyotrophic lateral sclerosis (Human molecular genetics (2015) 24 13 (3830-3846)). Human Molecular Genetics, 26 (17), 3452-3452. doi: 10.1093/hmg/ddx268
Lee, Albert, Rayner, Stephanie L., Gwee, Serene S. L., De Luca, Alana, Shahheydari, Hamideh, Sundaramoorthy, Vinod, Ragagnin, Audrey, Morsch, Marco, Radford, Rowan, Galper, Jasmin, Freckleton, Sarah, Shi, Bingyang, Walker, Adam K., Don, Emily K., Cole, Nicholas J., Yang, Shu, Williams, Kelly L., Yerbury, Justin J., Blair, Ian P., Atkin, Julie D., Molloy, Mark P. and Chung, Roger S. (2017). Pathogenic mutation in the ALS/FTD gene, CCNF, causes elevated Lys48-linked ubiquitylation and defective autophagy. Cellular and Molecular Life Sciences, 75 (2), 335-354. doi: 10.1007/s00018-017-2632-8
Shahheydari, Hamideh, Ragagnin, Audrey, Walker, Adam K., Toth, Reka P., Vidal, Marta, Jagaraj, Cyril J., Perri, Emma R., Konopka, Anna, Sultana, Jessica M. and Atkin, Julie D. (2017). Protein quality control and the amyotrophic lateral sclerosis/frontotemporal dementia continuum. Frontiers in Molecular Neuroscience, 10 119, 1-25. doi: 10.3389/fnmol.2017.00119
Walker, Adam K., Tripathy, Kalyan, Restrepo, Clark R., Ge, Guanghui, Xu, Yan, Kwong, Linda K., Trojanowski, John Q. and Lee, Virginia M. -Y. (2015). An insoluble frontotemporal lobar degeneration-associated TDP-43 C-terminal fragment causes neurodegeneration and hippocampus pathology in transgenic mice. Human Molecular Genetics, 24 (25), 7241-7254. doi: 10.1093/hmg/ddv424
Walker, Adam K., Spiller, Krista J., Ge, Guanghui, Zheng, Allen, Xu, Yan, Zhou, Melissa, Tripathy, Kalyan, Kwong, Linda K., Trojanowski, John Q. and Lee, Virginia M. -Y. (2015). Functional recovery in new mouse models of ALS/FTLD after clearance of pathological cytoplasmic TDP-43. Acta Neuropathologica, 130 (5), 643-660. doi: 10.1007/s00401-015-1460-x
Sundaramoorthy, Vinod, Walker, Adam K., Tan, Vanessa, Fifita, Jennifer A., Mccann, Emily P., Williams, Kelly L., Blair, Ian P., Guillemin, Gilles J., Farg, Manal A. and Atkin, Julie D. (2015). Defects in optineurin- and myosin VI-mediated cellular trafficking in amyotrophic lateral sclerosis. Human Molecular Genetics, 24 (13), 3830-3846. doi: 10.1093/hmg/ddv126
Walker, Adam K., Daniels, Christine M. LaPash, Goldman, James E., Trojanowski, John Q., Lee, Virginia M. -Y. and Messing, Albee (2014). Astrocytic TDP-43 pathology in Alexander disease. Journal of Neuroscience, 34 (19), 6448-6458. doi: 10.1523/JNEUROSCI.0248-14.2014
Atkin, Julie D., Farg, Manal A., Soo, Kai Ying, Walker, Adam K., Halloran, Mark, Turner, Bradley J., Nagley, Phillip and Horne, Malcolm K. (2014). Mutant SOD1 inhibits ER-Golgi transport in amyotrophic lateral sclerosis. Journal of Neurochemistry, 129 (1), 190-204. doi: 10.1111/jnc.12493
Kwong, Linda K., Irwin, David J., Walker, Adam K., Xu, Yan, Riddle, Dawn M, Trojanowski, John Q. and Lee, Virginia M. Y. (2014). Novel monoclonal antibodies to normal and pathologically altered human TDP-43 proteins. Acta Neuropathologica Communications, 2 (1) 33. doi: 10.1186/2051-5960-2-33
Walker, Adam K., Soo, Kai Y., Sundaramoorthy, Vinod, Parakh, Sonam, Ma, Yi, Farg, Manal A., Wallace, Robyn H., Crouch, Peter J., Turner, Bradley J., Horne, Malcolm K. and Atkin, Julie D. (2013). ALS-associated TDP-43 induces endoplasmic reticulum stress, which drives cytoplasmic TDP-43 accumulation and stress granule formation. PLoS One, 8 (11) e81170, e81170.1-e81170.12. doi: 10.1371/journal.pone.0081170
Sundaramoorthy, Vinod, Walker, Adam K., Yerbury, Justin, Soo, Kai Ying, Farg, Manal A., Hoang, Vy, Zeineddine, Rafaa, Spencer, Damian and Atkin, Julie D. (2013). Extracellular wildtype and mutant SOD1 induces ER-Golgi pathology characteristic of amyotrophic lateral sclerosis in neuronal cells. Cellular and Molecular Life Sciences, 70 (21), 4181-4195. doi: 10.1007/s00018-013-1385-2
Walker, Adam K., Soo, Kai Ying, Levina, Vita, Talbo, Gert H. and Atkin, Julie D. (2013). N-linked glycosylation modulates dimerization of protein disulfide isomerase family A member 2 (PDIA2). FEBS Journal, 280 (1), 233-243. doi: 10.1111/febs.12063
Farg, Manal A., Soo, Kai Y., Walker, Adam K., Pham, Hong, Orian, Jacqueline, Horne, Malcolm K., Warraich, Sadaf T., Williams, Kelly L., Blair, Ian P. and Atkin, Julie D. (2012). Mutant FUS induces endoplasmic reticulum stress in amyotrophic lateral sclerosis and interacts with protein disulfide-isomerase. Neurobiology of Aging, 33 (12), 2855-2868. doi: 10.1016/j.neurobiolaging.2012.02.009
Soo, Kai Y., Atkin, Julie D., Farg, Manal, Walker, Adam K., Horne, Malcolm K. and Nagley, Phillip (2012). Bim links ER stress and apoptosis in cells expressing mutant SOD1 associated with amyotrophic lateral sclerosis. PLoS One, 7 (4) e35413, e35413. doi: 10.1371/journal.pone.0035413
Walker, Adam K. and Atkin, Julie D. (2011). Stress signaling from the endoplasmic reticulum: a central player in the pathogenesis of amyotrophic lateral sclerosis. IUBMB Life, 63 (9), 754-763. doi: 10.1002/iub.520
Walker, Adam K. and Atkin, Julie D. (2011). Mechanisms of neuroprotection by protein disulphide isomerase in amyotrophic lateral sclerosis. Neurology Research International, 2011 317340. doi: 10.1155/2011/317340
Walker, Adam K. (2010). Protein disulfide isomerase and the endoplasmic reticulum in amyotrophic lateral sclerosis. Journal of Neuroscience, 30 (11), 3865-3867. doi: 10.1523/JNEUROSCI.0408-10.2010
Walker, Adam K., Farg, Manal A., Bye, Chris R., McLean, Catriona A., Horne, Malcolm K. and Atkin, Julie D. (2010). Protein disulphide isomerase protects against protein aggregation and is S-nitrosylated in amyotrophic lateral sclerosis. Brain, 133 (1), 105-116. doi: 10.1093/brain/awp267
Chung, Roger S., Penkowa, Milena, Dittmann, Justin, King, Carolyn E., Bartlett, Carole, Asmussen, Johanne W., Hidalgo, Juan, Carrasco, Javier, Leung, Yee Kee J., Walker, Adam K., Fung, Samantha J., Dunlop, Sarah A., Fitzgerald, Melinda, Beazley, Lyn D., Chuah, Meng I., Vickers, James C. and West, Adrian K. (2008). Redefining the role of metallothionein within the injured brain: Extracellular metallothioneins play an important role in the astrocyte-neuron response to injury. Journal of Biological Chemistry, 283 (22), 15349-15358. doi: 10.1074/jbc.M708446200
Chung, R. S., Fung, S. J., Leung, Y. K., Walker, A. K., McCormack, G. H., Chuah, M. I., Vickers, J. C. and West, A. K. (2007). Metallothionein expression by NG2 glial cells following CNS injury. Cellular and Molecular Life Sciences, 64 (19-20), 2716-2722. doi: 10.1007/s00018-007-7267-8