David Ashbrook

Baszucki Foundation Chancellor’s Fellow

Biography

Background

I am currently an Baszucki Foundation Chancellor’s Fellow in the Hub for Metabolic Psychiatry and Centre for Clinical Brain Sciences at the University of Edinburgh, and Associate Professor in the Department of Genetics, Genomics and Informatics, at the University of Tennessee Health Science Center, Memphis.

I graduated in 2011 from the University of Leeds with a BSc in Neuroscience, which included a year spent on industrial placement at AstraZeneca. I completed my PhD in Systems Biology at the University of Manchester's doctoral teaching centre in December 2015, where I had been supervised by Dr Reinmar Hager. I completed my first Postdoctoral Fellowship in the McGowan lab at the University of Toronto Scarborough, where I investigated the epigenetics of Gulf War Illness. I completed my second Postdoctoral Fellowship with Dr. Rob Williams at UTHSC, working on integrating multiple levels of sequencing data and a deep phenome in the BXD recombinant inbred mouse population.

My primary research interest is the brain, and its resultant behavioural phenotypes. I am intrigued by how genetic and cellular changes can be traced through a biological system to result in changes at the whole organism level, such as neuropsychiatric and neurodegenerative disorders, both of which are becoming an increasing health burden. The ability to produce and share massive datasets is one of the most exciting advancements in modern science because it enables a comprehensive systems approach to fundamental biological questions.

Other aspects of my work include the examination of indirect genetic effects and parent-of-origin effects on early life behaviour and developmental disorders, and the joint-analysis of phenotypes collected across species.

CV

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Qualifications

2011 – 2015, PhD Systems Biology, The University of Manchester, UK

Thesis title: ‘A systems-genetics analysis of complex phenotypes’

Supervisor: Dr. Reinmar Hager

External examiner: Dr. Darren Logan, Internal examiner: Dr. Kathryn Hentges

Developed methods to investigate the genetics and epigenetics underlying complex traits. This involved extensive behavioural analysis of early life interactions in mice.

2007 – 2011, BSc (Hons) Neuroscience (Ind), 2:1, The University of Leeds, UK 

Research project: Protein phosphorylation in Myshkin mice, a Na+,K+ ATPase α3 knockout strain, as a model of bipolar disorder.

Open to PhD supervision enquiries?

Yes

Current PhD students supervised

PhD students

2022 – Present, Main supervisor, Joy I. Afolabi (UTHSC)

 

Postdoctoral trainees

2023 – Present, Main supervisor, Postdoctoral Scholar, Mikhail Tiumentsev (UTHSC)

 

PhD Committees

2024– Present, Co-supervisor, Ernestine K Amos-Abanyie (UTHSC)

2022 – Present, Member of PhD Committee, Chris Rogers (UTHSC)

 

Past PhD students supervised

PhD students

2022 – 2025, Co-supervisor, Flavia Villani (UTHSC)

2022, Main supervisor, rotation project, Joseph Andrew Jones (UTHSC)

2020, Main supervisor, rotation project, Pamela M. Watson (UTHSC)

 

PhD Committees

2020 – 2024, Member of PhD Committee, Andrew B. Stiemke (UTHSC)

2022 – 2025, Member of PhD Committee, Panjun Kim (UTHSC)

2021 – 2024, Member of PhD Committee, Pamela M. Watson (UTHSC)

 

MD students

2025, Main supervisor, rotation project, Daphne Nallamala (UTHSC)

2023 – 2024, Main supervisor, rotation project, Zach Fontenot (UTHSC)

2023, Main supervisor, rotation project, Matthew Canonico (UTHSC)

2022, Main supervisor, rotation project, Wyatt A. Kaiser (UTHSC)

2021, Main supervisor, rotation project, Catherine L. Diethelm (UTHSC)

 

Undergraduate students

2023, Main Supervisor, Summer project, Saige A. Blanton (Christian Brothers University)

2021, Main Supervisor, Summer project, Alisha Chunduri

 

Research summary

It is abundantly clear that mental illnesses are not due to a single gene, neurotransmitter or cell type, but are complex, whole organism disorders modulated by many genes, environmental factors, and their interactions. This makes many traditional research approaches limited: in vitro assays cannot account for metabolic or immunological interactions between organs; human, clinical studies do not have the genetic or environmental control of lab studies, and we cannot perform invasive assays; traditional in vivo assays often only use a single genome of organism, and are therefore effectively an n of 1 – a single genome in a single environment repeatedly sampled – and do not reflect the genetic diversity of the human population. We require models that mirror the complexity of human patients.

My approach, experimental precision medicine, makes use of genetically diverse organisms, particularly mice, to produce models that allow whole organism identification of gene-gene and gene-environment interactions, across all organ systems, throughout the lifespan. This allows us to investigate the interactive effects of metabolism and severe mental illness – how interventions to alter one may have a feedback effect on the other. This provides an interventional mirror to Mendelian randomization and causal inference studies carried out on human populations.

We have seen repeatedly that findings in one strain of mouse often do not replicates across other strains, leading to both false positives and false negatives. If findings do not generalize within a species, how do we expect them to generalize across species to humans? By using a number of different strains, we can firstly identify effects that are generalizable (and therefore more likely to translate to humans), and secondly, identify outlier strains that can be further investigated to give insight into mechanisms of action (why might an intervention work for some people, but not others?).

Current project grants

R01AG075813-01 (Ashbrook) 01/01/2022 - 12/31/2026 NIH/NIA
The interaction effects of genetic variants, age, diet, sex and mitochondrial copy number on Alzheimer's disease, ageing-phenotypes and longevity
Role: Principal Investigator
Gene-by-environment study of the effects of age, sex and diet on mitochondrial DNA copy number, and its effects on longevity and Alzheimer’s disease related traits.

R01ES031656-01 (Jones) 04/01/2021 - 6/30/2026 NIH/NIEHS
Genetics of epigenetic response to high circulating glucocorticoids and organophosphorous compounds
Role: Co-investigator
Genetic and epigenetic study of stress and organophosphorous compounds as a model of Gulf War Illness, using the BXD recombinant inbred population.

R01CA262112-01 (Makowski) 04/01/2022 - 3/31/2027 NIH/NCI
Determining susceptibility loci in triple negative breast cancer using a novel pre-clinical model
Role: Co-investigator
Genetic study of modifiers of triple negative breast cancer phenotypes using a humanized mouse model, the TNBC-BXD strains.

U01CA272541-01 (Makowski) 09/01/2022 - 08/31/2027 NIH/NCI
Determining the contribution of microbial-derived metabolites to protective immunity in obesity-driven cancer risk
Role: Co-investigator
Gene-by-environment study to identify associations and test mechanisms of mediators of cancer risk in various pre-clinical models along an “obesity-microbes-metabolites- protective immunity” axis.

507021 (Nieman) 04/01/2024-04/01/2029 CIHR
Genetic determinants of radiation-induced brain toxicity in a juvenile mouse model
Role: Co-Applicant
Test genetic effects on long term response to whole brain radiation treatment using the BXD family, identifying loci contributing to resilience and susceptibility

313367/Z/24/Z (Lerch) 10/01/2024-04/01/2026 Wellcome Trust
Sensitising brain MRI to cell type and shape
Role: Key Collaborator
We will develop novel molecular MRI methods to be able to identify brain cell type numbers, shapes and connectivity, using BXD strains as our test cases.

Past project grants

2011-2015 1088088 via Systems Biology Doctoral Training Centre BB/G530225/1. A systems genetics analysis of complex traits in mouse and human model systems. Role: Award Holder (100% effort).

U01DA047638-01A1 (Chen/Williams) 04/01/2019 - 3/31/2024 NIH/NIDA
Systems genetics of menthol and nicotine addiction
Role: Co-Investigator
Genetic studies of addiction using hybrid rat diversity panel (HRDP) genetic reference population. We are using the HRDP to identify sequence variants that control motivational effects of nicotine with a menthol cue.

R01AG070913-01 (Williams/Johnson) 02/01/2021 - 8/31/2026 NIH/NIA
Imaging genetics of brain structure and cognitive aging in murine models of Alzheimer's Disease
Role: Co-investigator
Genetic study of the physiological and behavioural features of Alzheimer’s and their genetic modifiers, using the BXD recombinant inbred population and AD-BXD population.

Invited speaker

School of Biomedical Sciences Seminar Series, University of Leeds, Leeds, UK, 27 March 2025

  • Invited speaker, ‘The effects of genetic background on Alzheimer's related traits in a mouse model’

 

Integrative Physiology Colloquium, University of Colorado Boulder, Boulder, CO, USA, 8 April 2024

  • Invited speaker, ‘The importance of genetic background for model organism genetics’

 

Center for In Vivo Microscopy (CIVM) Seminar Series, Duke University, Durham, USA, virtual, 4 March 2022

  • Talk: ‘The importance of genetic background for model organism genetics, using the AD-BXD Alzheimer’s disease model’
  • Invited talk to about our collaboration with Duke, and the background to it

 

UTHSC Center for Cancer Research Symposium, Memphis, USA, 3 December 2021

  • Talk: ‘Including genetic complexity in models of disease’
  • Invited talk to cancer research community on how and why to include genetics in their rodent models

 

Neuroscience 2021, Society for Neuroscience meeting 2021, virtual, 8-11 November 2021

 

 

Organiser

20th Annual Meeting of the Complex Trait Community (CTC) and the Rat Genomics & Models Community, University of Tennessee Health Science Center, Memphis, TN, USA, 7-12 October 2023

  • Co-host and organizer
  • Session chair, ‘Machine learning for rodent behavior’

 

Genes, Brain, and Behavior Meeting 2023, University of Galway, Galway, Ireland, 22-25 May 2023

  • Poster: ‘Imaging genetics of brain structure and connectome in murine models of aging’
  • Program committee member

 

Genes, Brain, and Behavior Meeting 2022, Memphis, USA, 23-27 May 2022

  • Symposium: ‘Revolutionary genomics: Third-generation sequencing and pangenome approaches to understanding genes and behavior’
  • Local organizing committee member

 

 

Participant

38th International Mammalian Genome Society Conference, Glasgow, Scotland, UK, 6-9 April 2025

  • Talk: ‘Genetic modulation of neuroanatomy, mitochondrial function, and behaviour in the AD-BXD mouse model of Alzheimer's Disease’

 

21st annual meeting of the Complex Trait Community in collaboration with the Rat Genomics Community, Medical College of Wisconsin, Milwaukee, WI, USA, 2-5 October 2024

  • Poster, ‘Mouse Longevity App – an ongoing project to collect and make available mouse lifespan data’

 

The Allied Genetics Conference, Gaylord National Resort & Convention Center, Metro Washington, DC, USA, 6-10 March 2024

  • PhD student poster, ‘Machine learning for quantification of behavior in rodent models of aging and Alzheimer’s disease’
  • Postdoctoral trainee poster, ‘Mitochondrial phenotypes in BXD models of aging and Alzheimer’s disease’

 

International Mouse Phenotyping Consortium (IMPC) Annual International Conference, The Power of Mouse Genetics: Opportunities for Genomic and Precision Medicine, Keble College, Oxford, UK, 9-11 July 2023

  • Poster: ‘Massive diallel crosses (DAX) as a tool for investigating gene-by-gene-by-environment interactions, genetic background effects, and experimental precision medicine’

 

National Institute on Drug Abuse (NIDA) Genetics and Epigenetics Meeting 2023, National Institutes of Health (NIH), Bethesda, USA, 16-17 May 2023

  • Poster: ‘Good wine and old data get better with age: New insights on gene-by-environment effects of drugs of abuse in mice using GeneNetwork.org’

 

19th Annual Meeting of the Complex Trait Community (CTC) and the Rat Genomics & Models Community, University of Colorado Anschutz Medical Campus, Aurora, USA, 29-30 September 2022

  • Talk: ‘A novel pre-clinical model identifies genetic modifiers of triple negative breast cancer risk and progression’

 

 

 

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