NHMRC CJ Martin Fellow
Biomedical Sciences, Faculty of Medicine and Health Sciences
Dr Walker is a neurobiologist focused on uncovering the pathogenic mechanisms of motor neuron disease and frontotemporal dementia. He obtained his BSc(Hons) in Biochemistry from the University of Tasmania (2005), and his PhD in Neuroscience from the Florey Institute of Neuroscience and Mental Health at the University of Melbourne (2011). Most recently, with support from an NHMRC CJ Martin Overseas Postdoctoral Fellowship, Dr Walker was based in the laboratory of Professor Virginia Lee at the University of Pennsylvania, USA (2011-2015). He returned to Australia and joined Macquarie University in October, 2015.
BSc(Hons) – University of Tasmania (2005), PhD – University of Melbourne (2011)
Neurodegenerative diseases are characterised by accumulation of specific pathology in affected brain and spinal cord regions. TDP-43 is the essential DNA/RNA-binding protein that forms this pathology in most patients with either of two devastating neurodegenerative diseases: motor neuron disease (MND, causing rapid paralysis leading to death) and frontotemporal dementia (FTD, causing progressive debilitating changes in personality, behaviour, and/or language). However, how TDP-43 dysfunction causes disease remains unknown.
In recent studies, Dr Walker developed innovative new TDP-43 transgenic mice that for the first time show the key progressive pathological, neurodegenerative and behavioural features of human MND and FTD. Excitingly, his recent research in these mice shows that dramatic recovery of movement and greatly extended survival is possible if accumulated pathology is cleared, even at late disease stages. These findings provide hope that future disease-modifying therapeutics will be effective in patients even after the disease has advanced, due to the exquisite ability of the nervous system to recover from insult.
Dr Walker uses transgenic mice, in conjunction with studies of cell cultures and human autopsy material, to identify the key biochemical determinants of disease onset and progression and to test potential new therapeutics. His research uses a wide range of molecular biology, biochemical, cell biology, imaging and in vivo techniques. He is an enthusiastic and experienced mentor, and welcomes discussions with potential MRes/PhD students on available research projects covering a broad range of topics aimed at uncovering new ways to treat human disease.
- Walker AK, Spiller KJ, Ge G, Zheng A, Xu Y, Zhou M, Tripathy K, Kwong LK, Trojanowski JQ, Lee VM-Y (2015), ‘Functional recovery in new mouse models of ALS/FTLD after clearance of pathological cytoplasmic TDP-43’, Acta Neuropathologica, 130(5): 643-660.
- Walker AK*, Tripathy K*, Restrepo C, Ge G, Xu Y, Kwong LK, Trojanowski JQ, Lee VM-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. (*equal contribution)
- Walker AK*, LaPash Daniels CM*, Goldman JE, Trojanowski JQ, Lee VM-Y, Messing A, (2014) ‘Astrocytic TDP-43 pathology in Alexander disease’, The Journal of Neuroscience, 34(19): 6448-6458. (*equal contribution)
- Walker AK, Soo KY, Sundaramoorthy V, Parakh S, Ma Y, Farg MA, Wallace RH, Crouch PJ, Turner BJ, Horne MK, Atkin JD, (2013) ‘ALS-associated TDP-43 induces endoplasmic reticulum stress, which drives cytoplasmic TDP-43 accumulation and stress granule formation’, PLoS One, 8(11): e81170.
- 2012-2013 (USA) and 2015-2017 (Australia) NHMRC CJ Martin Overseas Biomedical Research Fellowship (1036835), Investigating mechanisms of dementia and motor neuron disease - $303,924
- 2016 Motor Neuron Disease Research Institute of Australia, Cure for MND Foundation Research Grant, Pre-clinical therapeutic testing and biochemical changes associated with neuron survival in a validated TDP-43 mouse model of MND - $99,984
- 2016 Alzheimer’s Australia Dementia Research Foundation Project Grant, Neuroinflammation in frontotemporal dementia: the role of microglia in TDP-43-related disease - $50,000
- 2016-2017 Macquarie University Research Development Grant, Identification of the biochemical determinants of neuron death and survival in a new mouse model of motor neuron disease - $49,825