Profiles

Duncan Sinclair

UTAS Home Dr Duncan Sinclair

Duncan Sinclair

Lecturer
Wicking Dementia Research & Education Centre

Room Room 417J (Level 4), Medical Science 1, Hobart CBD Campuses

+61 3 6226 6973 (phone)

duncan.sinclair@utas.edu.au

Dr Duncan Sinclair is a lecturer in the Wicking Dementia Research and Education Centre. He was previously a National Health and Medical Research Council CJ Martin ECR Fellow (2014-2017). Duncan’s work focusses on the molecular, cellular, genetic and lifestyle factors which determine how people respond to stress as they age, and how these factors influence the emergence and progression of dementia.

Biography

Duncan has a BSc (Hons I) from the University of Technology, Sydney and a PhD in psychiatry from the University of New South Wales. After completing his PhD he worked in postdoctoral positions at the University of Pennsylvania (Philadelphia, USA) and Neuroscience Research Australia (Sydney) focusing on the neurobiology of stress in the context of neurodevelopmental disorders such as schizophrenia and Fragile X syndrome. Since moving to Tasmania to join the Wicking Centre in 2017 he has worked on understanding the links between life stress and dementia while teaching in the Bachelor of Dementia Care degree.

Career summary

Qualifications

PhD        
Molecular stress signalling in human psychiatric illness and cortical development
University of New South Wales, Australia              
26/3/2012

BSc (Hons class 1)
University of Technology, Sydney, Australia          
30/11/2003

Languages (other than English)

Conversational Spanish

Memberships

Professional practice

Society for Neuroscience

Administrative expertise

Graduate Research Coordinator, Wicking Dementia Research and Education Centre

Member, UTAS institutional biosafety committee

Teaching

Teaching expertise

Unit coordinator for various units within the Bachelor of Dementia Care, including CAD004 (Neurospeak- Understanding the Nervous System) and CAD304 (Negotiated Project in Dementia).

Research Appointments

NHMRC CJ Martin ECR Fellow (2014-2017)

View more on Dr Duncan Sinclair in WARP

Expertise

  • Molecular assays (gene expression, proteomics, molecular signalling)
  • In vitro cell culture of human and non-human primary cells and cell lines
  • Animal models of neurodegenerative diseases and neurodevelopmental disorders- mouse behaviour and electroencephalography

Research Themes

Stressful experiences, including acute trauma and chronic stress, are inescapable in modern life and result in changes to the brain which mirror those seen in dementia. Life stress can increase risk for dementia and elevated levels of stress hormones are a feature of some types of dementia, yet the roles of stress in the emergence and progression of dementia are not understood. Duncan works with human cultured cells, post-mortem tissues and volunteer participants to investigate how responses to life stress change with age and influence the structure and function of the brain. He is particularly interested in stress-related factors (molecular, cellular, genetic and lifestyle) which influence a person’s resilience, modify their risk of dementia, contribute to dementia pathology and could be targeted therapeutically to promote healthy aging.

A complete list of Duncan’s publications can be found here.

Current projects

  1. Mechanisms underpinning the impacts of stress on Alzheimer’s disease pathology. In this project, supported by Dementia Australia, we are investigating the reciprocal interactions between stress hormones and amyloid beta, a peptide which aggregates in the brain in Alzheimer’s disease. We are using a range of in-vitro cell models including human neurons differentiated from induced pluripotent stem cells in collaboration with Dr Anthony Cook, and neural cells harvested from the olfactory neuroepithelium of adult donors in collaboration with Prof. Alan Mackay-Sim (Griffith University).
  2. Emergence of stress hormone abnormalities in a mouse model of amyloid pathology. In this project we are determining the age at which abnormal stress responsiveness and heightened stress hormone (corticosterone) levels emerge relative to amyloid accumulation in the brains of APP/PS1 mice.
  3. Health and resilience in the face of trauma. In this project, supported by at UTAS Community Engagement Grant, we are working alongside communities in Tasmania to explore the potential of a prospective longitudinal study of trauma exposure, resilience, health and aging. In this exploratory phase we are consulting with community members and groups to identify individual and community needs and develop a framework for co-design of a future study. This is a collaboration with researchers across UTAS including from the Australian Maritime College and the College of Science and Engineering.

Fields of Research

  • Cellular Nervous System (110902)
  • Central Nervous System (110903)
  • Neurosciences (110999)
  • Public Health and Health Services (111799)
  • Environmental and Occupational Health and Safety (111705)
  • Epidemiology (111706)

Research Objectives

  • Nervous System and Disorders (920111)
  • Neurodegenerative Disorders Related to Ageing (920112)
  • Specific Population Health (excl. Indigenous Health) (920599)
  • Infectious Diseases (920109)

Publications

A complete list of Duncan’s publications can be found here.

Total publications

18

Journal Article

(18 outputs)
YearCitationAltmetrics
2019Zieba J, Sinclair D, Sebree T, Bonn-Miller M, Gutterman D, et al., 'Cannabidiol (CBD) reduces anxiety-related behavior in mice via an FMRP-independent mechanism', Pharmacology Biochemistry and Behavior, 181 pp. 93-100. ISSN 0091-3057 (2019) [Refereed Article]

DOI: 10.1016/j.pbb.2019.05.002 [eCite] [Details]

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2018Olaya JC, Heusner CL, Matsumoto M, Sinclair D, Kondo MA, et al., 'Overexpression of Neuregulin 1 Type III Confers Hippocampal mRNA Alterations and Schizophrenia-Like Behaviors in Mice', Schizophrenia Bulletin, 44, (4) pp. 865-875. ISSN 0586-7614 (2018) [Refereed Article]

DOI: 10.1093/schbul/sbx122 [eCite] [Details]

Citations: Web of Science - 3

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2017Glass LJ, Sinclair D, Boerrigter D, Naude K, Fung SJ, et al., 'Brain antibodies in the cortex and blood of people with schizophrenia and controls', Translational psychiatry, 7, (8) pp. 1-9. ISSN 2158-3188 (2017) [Refereed Article]

DOI: 10.1038/tp.2017.134 [eCite] [Details]

Citations: Scopus - 3Web of Science - 3

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2017Sinclair D, Featherstone R, Naschek M, Nam J, Du A, et al., 'GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and Behavioral Deficits in the Fmr1 Knockout Mouse Model of Fragile X Syndrome', eNeuro, 4, (1) pp. 1-13. ISSN 2373-2822 (2017) [Refereed Article]

DOI: 10.1523/ENEURO.0380-16.2017 [eCite] [Details]

Citations: Scopus - 17Web of Science - 17

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2016Egbujo CN, Sinclair D, Hahn C-G, 'Dysregulations of synaptic vesicle trafficking in Schizophrenia', Current Psychiatry Reports, 18, (8) Article 77. ISSN 1523-3812 (2016) [Refereed Article]

DOI: 10.1007/s11920-016-0710-5 [eCite] [Details]

Citations: Scopus - 19Web of Science - 17

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2016Sinclair D, Cesare J, McMullen M, Carlson GC, Hahn CG, et al., 'Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus', Journal of Neurodevelopmental Disorders, 8 Article 14. ISSN 1866-1947 (2016) [Refereed Article]

DOI: 10.1186/s11689-016-9148-7 [eCite] [Details]

Citations: Scopus - 3Web of Science - 4

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2015Borgmann-Winter K, Willard SL, Sinclair D, Mirza N, Turetsky B, et al., 'Translational potential of olfactory mucosa for the study of neuropsychiatric illness', Translational psychiatry, 5 Article e527. ISSN 2158-3188 (2015) [Refereed Article]

DOI: 10.1038/tp.2014.141 [eCite] [Details]

Citations: Scopus - 23Web of Science - 19

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2015Egbujo CN, Sinclair D, Borgmann-Winter KE, Arnold SE, Turetsky BI, et al., 'Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia', Schizophrenia Research, 168, (1-2) pp. 554-562. ISSN 0920-9964 (2015) [Refereed Article]

DOI: 10.1016/j.schres.2015.07.026 [eCite] [Details]

Citations: Scopus - 8Web of Science - 8

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2014Fillman SG, Sinclair D, Fung SJ, Webster MJ, Weickert CS, 'Markers of inflammation and stress distinguish subsets of individuals with schizophrenia and bipolar disorder', Translational Psychiatry, 4 pp. 1-10. ISSN 2158-3188 (2014) [Refereed Article]

DOI: 10.1038/tp.2014.8 [eCite] [Details]

Citations: Scopus - 79Web of Science - 76

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2014Sinclair D, Purves-Tyson TD, Allen KM, Weickert CS, 'Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain', Psychopharmacology, 231, (8) pp. 1581-1599. ISSN 0033-3158 (2014) [Refereed Article]

DOI: 10.1007/s00213-013-3415-z [eCite] [Details]

Citations: Scopus - 77Web of Science - 68

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2013Catts VS, Fung SJ, Long LE, Joshi D, Vercammen A, et al., 'Rethinking schizophrenia in the context of normal neurodevelopment', Frontiers in cellular neuroscience, 7 Article 60. ISSN 1662-5102 (2013) [Refereed Article]

DOI: 10.3389/fncel.2013.00060 [eCite] [Details]

Citations: Scopus - 107Web of Science - 100

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2013Sinclair D, Fillman SG, Webster MJ, Weickert CS, 'Dysregulation of glucocorticoid receptor co-factors FKBP5, BAG1 and PTGES3 in prefrontal cortex in psychotic illness', Scientific reports, 3 pp. 1-10. ISSN 2045-2322 (2013) [Refereed Article]

DOI: 10.1038/srep03539 [eCite] [Details]

Citations: Scopus - 35Web of Science - 33

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2012Sinclair D, Fullerton JM, Webster MJ, Shannon Weickert C, 'Glucocorticoid receptor 1B and 1C mRNA transcript alterations in schizophrenia and bipolar disorder, and their possible regulation by GR gene variants', PloS one, 7, (3) ISSN 1932-6203 (2012) [Refereed Article]

DOI: 10.1371/journal.pone.0031720 [eCite] [Details]

Citations: Scopus - 37Web of Science - 37

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2012Sinclair D, Webster MJ, Fullerton JM, Weickert CS, 'Glucocorticoid receptor mRNA and protein isoform alterations in the orbitofrontal cortex in schizophrenia and bipolar disorder', BMC psychiatry ISSN 1471-244X (2012) [Refereed Article]

DOI: 10.1186/1471-244X-12-84 [eCite] [Details]

Citations: Scopus - 34Web of Science - 29

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2011Sinclair D, Tsai SY, Woon HG, Weickert CS, 'Abnormal glucocorticoid receptor mRNA and protein isoform expression in the prefrontal cortex in psychiatric illness', Neuropsychopharmacology, 36, (13) pp. 2698-2709. ISSN 0893-133X (2011) [Refereed Article]

DOI: 10.1038/npp.2011.160 [eCite] [Details]

Citations: Scopus - 28Web of Science - 24

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2011Sinclair D, Webster MJ, Wong J, Weickert CS, 'Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development', Molecular Psychiatry, 16, (5) pp. 504-515. ISSN 1359-4184 (2011) [Refereed Article]

DOI: 10.1038/mp.2010.28 [eCite] [Details]

Citations: Scopus - 38Web of Science - 42

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2009Weickert CS, Elashoff M, Richards AB, Sinclair D, Bahn S, et al., 'Transcriptome analysis of male-female differences in prefrontal cortical development', Molecular Psychiatry, 14, (6) pp. 558-561. ISSN 1359-4184 (2009) [Contribution to Refereed Journal]

DOI: 10.1038/mp.2009.5 [eCite] [Details]

Citations: Scopus - 62Web of Science - 58

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2004Ellis J, Sinclair D, Morrison D, 'Microarrays and stage conversion in Toxoplasma gondii', Trends in Parasitology, 20, (6) pp. 288-295. ISSN 1471-4922 (2004) [Refereed Article]

DOI: 10.1016/j.pt.2004.04.006 [eCite] [Details]

Citations: Scopus - 8Web of Science - 5

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Grants & Funding

Funding Summary

Number of grants

3

Total funding

$149,692

Projects

Developing isogenic iPSC lines to understand the role of stress hormones in Alzheimer s disease (2019)$20,000
Description
The aim of this project is to generate and characterize an isogenic control line from a famifia) AD iPSC line using CRISPR/Cas gene editing. This will yield a powerful tool to study impacts of intracellular AD processes on stress signaling and for future studies of AD pathology at the WickingCentre.
Funding
University of Tasmania ($20,000)
Scheme
Grant-Research Enhancement Program
Administered By
University of Tasmania
Research Team
Sinclair D; Cook AL
Year
2019
How does stress impact pathological processes in Alzheimer's disease? (2018)$50,000
Description
This study will determine how glucocorticoid stress signaling influences Aβ processing (and vice versa) in primary neurons from APP/PS1 transgenic mice and wildtype controls.
Funding
Dementia Australia Research Foundation Ltd ($50,000)
Scheme
Grant-Dementia Grants Program
Administered By
University of Tasmania
Research Team
Sinclair D; King AE; Vickers JC
Year
2018
Investigating NMDA receptor hypofunction as a point of convergence for genetic and environmental risk factors in schizophrenia (2017)$79,692
Description
This project will investigate two key pathways implicated in schizophrenia- glutamatergic (excitatory) neurotransmission and stress signalling- using post-mortem tissue, neuronal-like cells derived from living people, and brain tissues from Sandy mice. We will investigate how stress may impact the brain in schizophrenia, and how glutamatergic abnormalities emerge across the lifespan in the presence or absence of early-life stress, shedding light on how schizophrenia risk pathways converge.
Funding
National Health & Medical Research Council ($79,692)
Scheme
Fellowship-Early Career
Administered By
University of Tasmania
Research Team
Sinclair D
Year
2017
Grant Reference
1072878

How does stress impact pathological processes in Alzheimer's disease? (2018)$50,000

Funding:     Dementia Australia Research Foundation Ltd ($50,000)

Scheme:     Grant-Dementia Grants Program

Research Team:     Sinclair D; King AE; Vickers JC

Year:     2018