Mechanisms of Neurodegeneration Lab
- Key terms | Research goal and overview | Projects | Project funding | Publications
Brain Imaging, biomarkers, magnetic resonance imaging, positron emission tomography, neurodegeneration, ataxia, cerebellum
Dr Will Khan
Phone: +61 3 9905 9283
To apply brain imaging techniques to comprehensively characterise neurobiology in individuals with rare neurodegenerative diseases, and to identify biomarkers of disease progression and treatment efficacy.
Our research group uses magnetic resonance imaging (MRI) and positron emission tomography (PET) to investigate and track brain changes in people with neurodegenerative diseases. This work principally focusses on individuals with inherited subcortical diseases, including Friedreich ataxia, Spinocerebellar ataxias, and Huntington’s disease. Additional work in other neurodegenerative disorders and in preclinical animal models is also being undertaken with our collaborators.
The broad aims of our research include:
- Biological phenotyping, such as describing changes in brain structure and function, and
- Mechanistic inferences, including cellular/molecular-level measurements of inflammation, oxidative stress, and metabolic dysfunction.
See also the available research projects for students.
Mechanistic Neuroimaging of Neuroinflammation and Oxidative Stress in Neurodegenerative Diseases
- Our flagship research program uses hybrid MRI/PET technology, investigational PET radiotracers, and blood markers to investigate pathological processes and sub-cellular measures of disease expression and progression. The techniques we employ are sensitive to neuroinflammation, oxidative stress/ferroptosis, iron homeostasis, vascular health, and systems-level brain structure and function.
- Within this program, we are currently recruiting people with Friedreich ataxia and Spinocerebellar Ataxia Types 1, 2, 3, and 6.
ENIGMA-Ataxia - A Global MRI Collaboration for Rare Cerebellar Diseases
- Our group coordinates the ENIGMA-Ataxia international working group (http://enigma.ini.usc.edu/ongoing/enigma-ataxia/).
- Inherited ataxias are rare diseases, leading to most published literature relying on small sample sizes with limited statistical power, reliability, and generalisability. ENIGMA-Ataxia was founded to harmonise and aggregate the analysis of existing MRI data in these diseases from around the world in order to pool our collective resources and overcome many of these limitations.
- The working group currently consists of 19 data sites and 3 methods groups from Australia, North and South America, and Western Europe. Analysis of brain morphometry, white mater integrity, and spinal cord structure are currently underway.
Cerebellar Function & Connectivity
- The human cerebellum is known to contribute to a broad range of motor, cognitive, and affective behaviours. However, the role of the cerebellum in nonmotor functions, in particular, is not yet well understood.
- Using functional MRI data and cognitive testing, our group investigates the function and large-scale connectivity of the cerebellum in healthy populations and individuals with cerebellar diseases.
STAREE Neuroimaging Substudy
- The STAtins in Reducing Events in the Elderly (STAREE) clinical trial is a large-scale study of the health impacts of statins in 10,000+ heathy individuals over the age of 70 years.
- Our team is leading the STAREE Neuroimaging sub-study of 200 of these individuals, using a suite of MRI measures of brain morphometry, white matter integrity, and vascular health.
Current project funding
- NHMRC Ideas Grant, 2020-24, Neurodegeneration in Spinocerebellar Ataxias: Biomarkers, Mechanisms, and Variability
- Friedreich Ataxia Research Alliance (USA), 2019-21, Neuroinflammation in Friedreich Ataxia: Mechanism, Biomarker, and Therapeutic Target
- Takeda Pharmaceuticals, 2020-21, Investigator-Initiated Collaborative Research: ENIGMA-Ataxia Research Consortium
Selected recent publications (2016-2021)
- Harding IH, Chopra S, Arrigoni F, .... , Egan GF, Thompson PM. Brain Structure and Degeneration Staging in Friedreich Ataxia: Magnetic Resonance Imaging Volumetrics from the ENIGMA-Ataxia Working Group. Ann Neurol. 2021 Aug 26. doi: 10.1002/ana.26200. Epub ahead of print. PMID: 34435700.
- Selvadurai LP, Corben LA, Delatycki MB, Stagnitti MR, Storey E, Egan GF, Georgiou-Karistianis N, Harding IH. (2020). Multiple mechanisms underpin cerebral and cerebellar white matter deficits in Friedreich ataxia: The IMAGE-FRDA study. Human Brain Mapping. 41(7): 1920-33.
- Poudel GR, Harding IH, Egan GF, Georgiou-Karistianis N. (2019). Network spread determines severity of degeneration and disconnection in Huntington’s disease. Human Brain Mapping. 40(14): 4192-4201.
- Ward PGD, Harding IH, Close T, Corben LA, Delatycki MB, Storey E, Georgiou-Karistianis N, Egan GF. (2019). Longitudinal evaluation of iron concentration and atrophy in the dentate nuclei in Friedreich ataxia. Movement Disorders 34(3): 335-343.
- Harding IH, Corben LA, Delatycki MB, Stagnitti MR, Storey E, Egan GF, Georgiou-Karistianis N. (2017). Cerebral compensation during motor function in Friedreich ataxia: The IMAGE-FRDA study. Movement Disorders 32(8): 1221-1229.
- Harding IH*, Selvadurai LP*, Corben LA, Stagnitti MR, Storey E, Egan GF, Delatycki MB, Georgiou-Karistianis N. (2016). Cerebral and cerebellar grey matter atrophy in Friedreich ataxia: The IMAGE-FRDA study. J Neurology 263(11): 2215-2223.
- Harding IH, Raniga P, Delatycki MB, Stagnitti MR, Corben LA, Storey E, Georgiou-Karistianis N, Egan GF. (2016). Tissue atrophy and elevated iron concentration in the extrapyramidal motor system in Friedreich ataxia: The IMAGE-FRDA study. J Neurology Neurosurgery and Psychiatry 87: 1261-1263.
- Harding IH, Corben LA, Storey E, Egan GF, Stagnitti MR, Poudel GR, Delatycki MB, Georgiou-Karistianis N. (2016). Fronto-cerebellar dysfunction and dysconnectivity underlying cognition in Friedreich ataxia: The IMAGE-FRDA study. Human Brain Mapping 37: 338-350.