Our People

Michelle Lupton

Associate Professor | Senior Research Officer

Genetic Epidemiology

Michelle.Lupton@qimrberghofer.edu.au

WORK HISTORY

Associate Professor Lupton’s main area of expertise is genetics of Alzheimer’s disease (AD). She have a strong track record in GWAS and sequencing studies. She have contributed to the major discoveries in AD genetics of the past decade, including the identification of the first genome wide significant genetic risk variants outside of APOE, and the large scale AD GWAS meta-analyses. She had an active role in the discovery of TREM2, identified through exome sequencing to be a rare variant with a large effect size on AD risk. These studies identified pathophysiological pathways in AD, including highlighting inflammatory response as causative. Genetic discoveries have a great impact on the understanding of disease aetiology and informing treatment strategies. Her previous work in AD cohort studies, and recent leading role in the PISA study (Prospective Neuroimaging Study of Aging) have, and will continue to greatly contribute to the identification of biomarkers for AD, including neuroimaging, neuropsychology and blood based markers.

RECENT PUBLICATIONS

  • Mitchell BL, Thorp JG, Evans DM, Nyholt DR, Martin NG, Lupton MK. 2020. Exploring the genetic relationship between hearing impairment and Alzheimer’s disease. Alzheimers Dement (Amst). 2020 Sep 25;12(1):e12108.
  • Lupton MK, Robinson GA, Adam RJ, Rose S, Byrne GJ, Salvado O, Pachana NA, Almeida OP, McAloney K, Gordon SD, Raniga P, Fazlollahi A, Xia Y, Ceslis A, Sonkusare S, Zhang Q, Kholghi M, Karunanithi M, Mosley PE, Lv J, Borne L, Adsett J, Garden N, Fripp J, Martin NG, Guo CC, Breakspear M. A prospective cohort study of prodromal Alzheimer’s disease: Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA). Neuroimage Clin. 2021;29:102527. doi: 10.1016/j.nicl.2020.102527. Epub 2020 Dec 8.

Complete publications and citation information can be accessed here: Pubmed | Google Scholar

CURRENT APPOINTMENTS

2020-current: Honorary Senior Fellow, School of Biomedical Sciences, University of Queensland (UQ)

2018-current: Adjunct Associate Professor, School of Biomedical Sciences at the Queensland University of Technology (QUT) 

2017-current: Senior Research Officer in the Genetic Epidemiology group headed by Professor Nick Martin at QIMR Berghofer Medical Research Institute

PREVIOUS APPOINTMENTS

2015-2019: Visiting Academic in the Imaging Genomics Group at the Queensland Brain Institute and Centre for Advanced Imaging headed by Associate Professor Margie Wright at the University of Queensland

2015-2017: Research Officer, Neuroimaging Genetics, then transferred to Genetic Epidemiology, QIMR Berghofer

2009-2012: Post-doctoral Research Worker, Kings College London (KCL), UK 

2011-2012: Demonstrator for Advanced Research Methods, Psychology Undergraduate and Certificate Programme at Birkbeck University of London, UK 

2006-2009: MRC capacity building PhD Studentship in Neuroscience at KCL 

2004-2006: Research Assistant, Medical and Molecular Genetics, KCL 

ORCID NUMBER

0000-0002-7274-7299

CURRENT AREA OF RESEARCH

Associate Professor Lupton’s is the chief investigator on a recently secured AU$4M grant to assemble the largest ever dementia research cohort in Australia with the aim to develop a blood biomarker test to predict onset and progression of cognitive decline in dementia (NHMRC Medical Research Future Fund). She is currently Identifying blood based methylation markers associating with prodromal AD, to identify a specific methylation patterns directly related to AD risk which could be used as a diagnostic AD biomarker in midlife. As part of the PISA study she has spearheaded the use of genetic risk prediction to identify those at a higher risk of AD and in a prodromal disease stage. In addition, working with leaders in the field of psychiatric genetics (including group leader Prof Nick Martin) she also has used the latest advances in genetic methods to use polygenetic risk score and Mendelian Randomisation (MR) approaches to assess causal inference in AD. This work includes investigating the effect of peripheral iron levels (first author publication) and hearing impairment (senior author publication) on AD risk.

She is a recipient of a highly competitive NHMRC Boosting Dementia Leadership Fellowship and a Dementia Australia Project Grant, and a member of prominent international AD genetics consortia. They are currently working with the Australia Dementia Network (ADNeT) an NHMRC Boosting Dementia Research Initiative, in the development of the Brisbane arm of a nationwide Australian cohort of individuals, to function as a ‘standing cohort’ for participation in AD clinical trials.

 

RESEARCH HIGHLIGHTS

  • The investigation of genetic variation associated with AD in healthy individuals:

Associate Professor Lupton’s current research focus aims to improve understanding of the early effect of AD genetic risk factors, and identify biomarkers before clinical diagnosis. She is the Chief Investigator and the genetics and epidemiology analyst for the Prospective Imaging Study of Aging: Genes, Brain and Behaviour (PISA). She has designed participant selection for PISA using a polygenic risk score approach. She has also work on both elderly and young population based cohorts including OATS (Older Australian Twin Study), MAS (Sydney Memory and Aging Study) and QTIM (Queensland Twin Imaging) focusing on brain phenotypes including MRI measures. She uses polygenic risk score and Mendelian Randomization approaches to investigate causal relationships between phenotypes and co-morbid diseases.

  • Genome Wide Association Studies in AD

During her PhD and first post doc in the UK, Associate Professor Lupton’s worked with Prof John Powell, Prof Simon Lovestone, and Dr Angela Hodges at KCL on Alzheimer’s disease case/control cohorts with collaborations continuing to the present time. Cohorts included GERAD (Genetic and Environmental Risk in Alzheimer’s disease) led by Prof Julie Williams and AddNeuroMed (Innovative Medicines (InnoMed) in Europe). She has extensive wet lab experience and have coordinated DNA samples and datasets for these large cohorts, liaising with national and international collaborators. She is proficient in the analysis and imputation of GWAS data. She is also a member of IGAP (International Genomics of Alzheimer’s Project), a worldwide GWAS Meta-analysis consortium.

  • The contribution of rare genetic variation to AD

Associate Professor Lupton’s have carried out several sequencing studies including wet lab work in library preparation, and the use and development of data analysis pipelines. She is part of the AESG (Alzheimer’s Exome Sequencing Group) with Prof John Hardy at University College London and contributed to the exome sequencing study which identified the TREM2 risk variant for AD. She is also part of the GERAD consortium exome chip study which identified additional rare coding variants which are associated with AD risk, and further implicated the inflammation pathway in AD pathogenesis.

  • AD blood based biomarkers

Associate Professor Lupton’s have contributed to several AD biomarker studies and am currently working in this area in the PISA study and in collaboration with groups across Australia as part of a recently award NHMRC MRFF grant awarded in the Dementia, Aging and Age Care Mission where we will form the largest ever dementia research cohort in Australia with the aim to develop a blood biomarker test to predict onset and progression of cognitive decline in dementia. In addition she has secured funding to carry out genome-wide methylation analysis in the PISA cohort. With this work she aims to investigate the potential for DNA methylation in the blood as an easily accessible midlife prognostic biomarker for AD. She collaborates with Allan McRae (QBI), and Simon Laws (ABIL in Melbourne) on DNA methylation studies.

PROFESSIONAL MEMBERSHIPS

  • Member of the following societies: Australian Society for Medical Research (ASMR), the International Society to Advance Alzheimer’s Research and Treatment (ISTAART), the American Society of Human Genetics (ASHG), and the Australian Epigenetics Alliance (AEpiA).
  • Member of the ADNeT Early/Mid-career Accelerator Working Group (providing capacity building and career support to NNIDR’s cohort of Development Fellows in Australia). I am also a mentor for the NNIDR sponsorship program.
  • Member of the QIMRB Mental Health Education Committee and organiser of monthly QIMRB Mental Health Program Seminars.

AWARDS RECOGNITION

2018-2021: NHMRC Boosting Dementia Research Leadership Fellowship

2012-2016: QIMR Early Career Postdoctoral Fellowship from the Perpetual Foundation

2016: The Australian Society for Medical Research Senior Researcher Award Finalist

2011: International Congress of Human Genetics trainee research award semi-finalist

2009: Kings College London Health Schools graduate showcase oral presentation prize

CURRENT RESEARCH SUPPORT

  • NIH/NIA R01 “Advancing drug repositioning and development for Alzheimer’s Disease using functional genomics and computational phenomics” 2021 (2 years) (Co-Investigator)
  • Special Purpose Private Donation “Methylation-based biomarkers for prodromal Alzheimer’s disease”, QIMRB 2021
  • NHMRC Medical Research Future Fund (MRFF)-Dementia, Ageing and Aged Care Mission scheme “Blood testing to predict and discriminate dementias” 2021-2026
  • NHMRC Project grant “Genetic and lifestyle susceptibility and resilience factors affecting rates of change in preclinical Alzheimer’s disease” 2019-2021 (Associate Investigator).
  • NHMRC Boosting Dementia Leadership Fellowship. “Genetic Investigations for Prodromal Alzheimer’s disease” 2018-2022
  • NHMRC Boosting Dementia Research Initiative team grant “Prospective Imaging Study of Aging: Genes, Brain and Behaviour” 2019-2022 (Chief Investigator)

EDUCATIONAL BACKGROUND

2010: PhD Neuroscience, Kings College London (KCL), UK

2003: BSc Honours Human Genetics, University of Nottingham, UK