Dr Martin Lewis
2018 - Current Head, Neuropsychiatric Laboratory, Lifelong Health, SAHMRI
2014 - 2017 Senior Research Fellow, Mind & Brain Theme, SAHMRI
2009 - 2013 Chief Scientist, The Stroke Research Program, University of Adelaide / Queen Elizabeth Hospital
2005 - 2008 Research Fellow, The Centre for the Molecular Genetics of Development, University of Adelaide
2000 - 2004 Postdoctoral researcher, School of Pharmacy, University of South Australia
Project 1. Precision medicine for mental health
Approximately half of every population have natural gene variations that affect many of the medicines we use. Identifying the genetic variations for an individual can guide the dose or type of medicines prescribed. Matching of pharmaceuticals to particular genotypes is known as pharmacogenomics. It is estimated ~50% of patients do not respond to the first antidepressant they are prescribed. Access to accurate genetic testing, interpretation and translation into precision medicine is required to increase successful treatment responses.
A number of genetic analysis platforms are used to identify gene variations including microarrays, high resolution melt analysis, sanger-, second- and third- generation sequencing. The suitability of each analysis platform is dependent on the gene(s) of interest. Our laboratory is interested in long-read third generation sequencing technologies to better detect variations in genes with high homology to other genes. Variants are read from the sequence data, converted into allele types, genotypes and functional phenotypes.
The aim is improved genotyping for precision medicine in mental health services. This project offers individuals genetic testing to recommend precision medicine to guide clinical pharmacologists and prescribing physicians. Personalised prescriptions are particularly important for antidepressants and antipsychotics to decrease the length of time to optimise treatments. Our research team includes a neuroscientist and geneticist, psychiatric clinician, clinical pharmacologist and psychiatrists.
Contact Dr Lewis for details of this PhD project.
Project 2. Epigenetics and Major Depression
Chronic psychological stress often manifests itself as Major Depressive Disorder (MDD). Sustained stress can alter corticotrophin releasing hormone, adrenocorticotropic hormone and cortisol. The homeostasis of the hypothalamic-pituitary-adrenal (HPA) axis can become dysregulated by a number of maladaptive changes when this neuroendocrine system is kept under pressure.
Stressors in our environment have an impact on gene expression through epigenetic modifications to our chromosomes. One type of epigenetic change is the modification of histone proteins that pack our DNA into chromosomes. A regulator of gene expression PHF21B is associated with major depression. PHF21B belongs to a class of proteins that read epigenetic modifications on histones and respond by facilitating specific changes to gene expression. Our aim is to understand what cell signals regulate PHF21B and determine the set of genes expression changes mediated by this epigenetic reader.
The BMP antagonist Gremlin1 contributes to the development of cortical excitatory neurons, motor balance and fear responses. Mari Ichinose, Nobumi Suzuki, Tongtong Wang, Hiroki Kobayashi, Laura Vrbanac, Jia Q Ng, Josephine A Wright, Tamsin RM Lannagan, Krystyna A Gieniec, Martin Lewis, Ryota Ando, Atsushi Enomoto, Simon Koblar, Paul Thomas, Daniel L Worthley, Susan L Woods (2020). bioRxiv
Chronic stress induces hypersensitivity of murine gastric vagal afferents. Hui Li, Femke TA Buisman‐Pijlman, Maria Nunez‐Salces, Stewart Christie, Claudine L Frisby, Antonio Inserra, George Hatzinikolas, Martin D Lewis, Stamatiki Kritas, Ma‐Li Wong, Amanda J Page (2019). Neurogastroenterology & Motility https://doi.org/10.1111/nmo.13669
Mice lacking Casp1, Ifngr and Nos2 genes exhibit altered depressive-and anxiety-like behaviour, and gut microbiome composition. A Inserra, JM Choo, MD Lewis, GB Rogers, ML Wong, J Licinio (2019). Scientific Reports 9 (1), 6456 https://doi.org/10.1038/s41598-018-38055-8
Short-term antidepressant treatment has long-lasting effects, and reverses stress-induced decreases in bone features in rats. SH Lee, CA Mastronardi, RW Li, G Paz-Filho, EG Dutcher, MD Lewis, AD Vincent, PN Smith, SR Bornstein, J Licinio, ML Wong (2019). Translational Psychiatry 9 (1), 10 https://doi.org/10.1038/s41398-018-0351-z
Alterations in anxiety and social behaviour in Npas4 deficient mice following photochemically-induced focal cortical stroke. TS Klarić, EJ Jaehne, SA Koblar, BT Baune, MD Lewis (2017). Behavioural brain research 316, 29-37 https://doi.org/10.1016/j.bbr.2016.08.050
The PHF21B gene is associated with major depression and modulates the stress response. M-L Wong, M Arcos-Burgos, S Liu, J I Vélez, C Yu, B T Baune, MC Jawahar, V Arolt, U Dannlowski, A Chuah, GA Huttley, R Fogarty, MD Lewis, SR Bornstein and J Licinio (2017). Molecular Psychiatry 22, 1015-1025 https://doi.org/10.1038/mp.2016.174
miR-744 and miR-224 Downregulate Npas4 and Affect Lineage Differentiation Potential and Neurite Development During Neural Differentiation of Mouse Embryonic Stem Cells. FC Choy, TS Klarić, SA Koblar, MD Lewis (2017).
Molecular Neurobiology 54,3528-3541 https://doi.org/10.1007/s12035-016-9912-4
Inflammasome signaling affects anxiety-and depressive-like behavior and gut microbiome composition. ML Wong, A Inserra, MD Lewis, CA Mastronardi, L Leong, J Choo, S Kentish, P Xie, M Morrison, SL Wesselingh, GB Rogers, J Licinio (2016). Molecular psychiatry 21 (6), 797-805 https://doi.org/10.1038/mp.2016.46
Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia. FC Choy, TS Klarić, WK Leong, SA Koblar, MD Lewis (2016). Journal of Cerebral Blood Flow & Metabolism 36 (8), 1449-1463 https://doi.org/10.1177/0271678X15606146
Disparate Changes in Plasma and Brainstem Cytokine Levels in Adult and Ageing Rats Associated with Age-Related Changes in Facial Motor Neuron Number, Snout Muscle Morphology, and Exploratory Behavior. V Katharesan, MD Lewis, R Vink, IP Johnson (2016). Frontiers in Neurology 7 (191) https://doi.org/10.3389/fneur.2016.00191
The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia. FC Choy, TS Klarić, SA Koblar, MD Lewis (2015).
International Journal of Molecular Sciences 16 (12), 29011-29028 https://doi.org/10.3390/ijms161226144
Effects of Npas4 deficiency on anxiety, depression-like, cognition and sociability behaviour. EJ Jaehne, TS Klarić, SA Koblar, BT Baune, MD Lewis (2015). Behavioural Brain Research 281, 276-282 https://doi.org/10.1016/j.bbr.2014.12.044
Translational Research in Endocrinology and Neuroimmunology Applied to Depression. ML Wong, M Lewis, J Licinio (2015). Biomedical Chemistry: Current Trends and Developments., 119-131 https://doi.org/10.1515/9783110468755-004
Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain. T Klarić, M Lardelli, B Key, S Koblar, M Lewis (2014). Frontiers in Neuroanatomy 8, 148
Generating and measuring photochemical changes inside the brain using optical fibers: exploring stroke. Georgios Tsiminis, Thomas S Klarić, Erik P Schartner, Stephen C Warren-Smith, Martin D Lewis, Simon A Koblar, Tanya M Monro (2014). Biomedical Optics Express 5 (11), 3975-3980
A reduction in Npas4 expression results in delayed neural differentiation of mouse embryonic stem cells. TS Klaric, PQ Thomas, M Dottori, WK Leong, SA Koblar, MD Lewis (2014). Stem Cell Research & Therapy
Neurogenic potential of dental pulp stem cells isolated from murine incisors. KM Ellis, DC O'Carroll, MD Lewis, GY Rychkov, SA Koblar (2014). Stem cell research & therapy 5 (1), 1-13
Leong WK, Klaric TS, Lin Y, Koblar SA, Lewis MD (2013). Upregulation of the neuronal Per-Arnt-Sim domain protein 4 (Npas4) in the rat corticolimbic system following focal cerebral ischemia. Eur J Neuroscience 2013. https://doi.org/10.1111/ejn.12163
Holliday EG, Maguire JM, Evans T-J, Koblar SA, Jannes J, Sturm JW, Hankey GJ, Baker R, Golledge J, Parsons MW, McEvoy M, Biros E, Lewis MD, Lincz LF, Peel R, Oldmeadow C, Smith W, Moscato P, Barlera S, Bevan S, Bis JC, Boerwinkle E, Boncoraglio G, Brott TG, Brown RD, Jr, Cheng Y-C, Cole JW, Cotlarciuc I, Devan WJ, Fornage M, Furie KL, Grétarsdóttir S, Gschwendtner A, Ikram MA, Longstreth, WT, Jr, Malik R, Meschia JF, Mitchell BD, Mosley TH, Nalls MA, Parati EA, Psaty BM, Sharma P, Stefansson K, Thorleifsson G, Thorsteinsdottir U, Verhaaren BFJ, Wiggins KL, Worrall BB, Sudlow C, Rothwell PM, Farrall M, Dichgans M, Rosand J, Markus HS, Scott RJ, Levi C, Attia J. A locus on chromosome 6p21.1 is associated with large artery atherosclerotic stroke. Nature Genetics 2012 Oct;44(10):1147-51. doi:10.1038/ng.2397. Epub 2012 Sep 2. (IF 35.5)
Leong WK, Henshall TL, Arthur A, Kremer KL, Lewis MD, Helps SC, Field J, Hamilton-Bruce MA, Warming S, Manavis J, Vink R, Gronthos S, Koblar SA. Human Adult Dental Pulp Stem Cells Enhance Poststroke Functional Recovery Through Non-Neural Replacement Mechanisms. Stem Cells Translational Medicine 2012, 1(3) 177-187. doi:10.5966/sctm.2011-0039. Epub 2012 Feb 22.
Yu-Ching C, Anderson CD, Bione S, Keene K, Maguire JM, Nalls M, Rasheed A, Zeginigg M, Attia J, Baker R, Barlera S, Biffi A, Bookman E, Brott TG, Brown RD Jr, Chen F, Chen WM, Ciusani E, Cole JW, Cortellini L, Danesh J, Doheny K, Ferrucci L, Franzosi MG, Frossard P, Furie KL, Golledge J, Hankey GJ, Hernandez D, Holliday EG, Hsu FC, Jannes J, Kamal A, Khan MS, Kittner SJ, Koblar SA, Lewis MD, Lincz L, Lisa A, Matarin M, Moscato P, Mychaleckyj JC, Parati EA, Parolo S, Pugh E, Rost NS, Schallert M, Schmidt H, Scott RJ, Sturm JW, Yadav S, Zaidi M, GARNET Collaborative Research Group; GENEVA Consortium; Boncoraglio GB, Levi CR, Meschia JF, Rosand J, Sale M, Saleheen D, Schmidt R, Sharma P, Worrall B, Mitchell BD, on behalf of the International Stroke Genetics Consortium. Are myocardial infarction-associated single nucleotide polymorphisms associated with ischemic stroke? Stroke 2012, 43(4): 980-6. doi:10.1161/STROKEAHA.111.632075. Epub 2012 Feb 23.
Tran HB, Lewis MD, Tan LW, Lester SE, Baker LM, Ng J, Hamilton-Bruce MA, Hill CL, Koblar SA, Rischmueller M, Ruffin R, Wormald PJ, Zalewski PD and Lang CJ. Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes Following Induction of Ovalbumin-Induced Airway Inflammation. Journal of Allergy 2012, Article ID 819176. doi:10.1155/2012/8191762012
Manning JA, Lewis MD, Koblar SA, Kumar S. An essential function for the centrosomal protein NEDD1 in zebrafish development. Cell Death Differ. 2010, 17(8):1302-14. PubMed PMID: 20150915 (IF 7.548).
Roberts RR, Ellis M, Gwynne RM, Bergner AJ, Lewis MD, Beckett EA, Bornstein JC, Young HM. The first intestinal motility patterns in fetal mice are not mediated by neurons or interstitial cells of Cajal. J Physiol. 2010, 1;588(Pt 7):1153-69. PubMed PMID: 20142273 (IF 4.469).
Lewis MD, Roberts BJ. Role of CYP2E1 activity in endoplasmic reticulum ubiquitination, proteasome association, and the unfolded protein response. Arch Biochem Biophys. 2005, 436(2):237-45. PubMed PMID: 15797236 (IF 3.152).
Lewis MD, Roberts BJ. Role of the C-terminal alpha-helical domain of the von Hippel-Lindau protein in its E3 ubiquitin ligase activity. Oncogene. 2004, 23(13):2315-23. PubMed PMID: 14691445 (IF 6.872).
Lewis MD, Roberts BJ. Role of nuclear and cytoplasmic localization in the tumour-suppressor activity of the von Hippel-Lindau protein. Oncogene. 2003, 22(26):3992-7. PubMed PMID: 12821933 (IF 6.872).
Maguire J, Holliday E, Sturm J, Golledge J, Lewis MD, Koblar SA, Jannes J, Hankey G, Lincz L, Moscato P, Baker R, Parsons M, Scott R, Attia J and Levi C. Australian stroke genetics collaborative: Genetic associations with ischaemic stroke functional outcome. International Journal of Stroke 2011 6 SUPPL. 1 (44)
Djukic M, Lewis MD, Leung E, Jannes J, Hamilton-Bruce MA, Chataway TK and Koblar SA. Human plasma biomarker investigation of transient ischaemic attack (TIA) by 2D-differential in-gel electrophoresis (DIGE) and mass spectrometry: A pilot study. International Journal of Stroke 2011 6 SUPPL. 1 (42)
Tran H, Rischmueller M, Lester S, Tan LW, Lewis MD, Koblar SA, Lang C and Zalewski P. Inflammasome activation is implicated in disease pathogenesis in asthma and primary Sjogren's syndrome. Internal Medicine Journal 2011 41 SUPPL. 1 (9)
Djukic M, Lewis MD, Leung E, Hamilton-Bruce MA, Chataway TK and Koblar SA. Proteomic analysis of plasma following transient ischaemic attack (TIA). International Journal of Stroke. 2010 6 SUPPL. 1 (38)
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Entry last updated: Wednesday, 23 Sep 2020
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