Sinead O'Donovan, Ph.D.
Assistant Professor
Office: 183 Block Health Science Building
Tel: 419-383-5266
Email: Sinead.ODonovan@utoledo.edu
Education:
2018: Postdoctoral Fellow, Department of Psychiatry & Behavioral Neuroscience, University
of Cincinnati
2014: Postdoctoral Fellow, Institute of Neuroscience & Department of Psychiatry,
Trinity College of Dublin, Ireland
2012: Ph.D., Neuroscience, Institute of Neuroscience & Department of Psychiatry,
Trinity College of Dublin, Ireland
2007: B.A., Moderatorship in Natural Sciences (Neuroscience), Trinity College of
Dublin, Ireland
Research Interests:
My research focus is on gaining a greater understanding of pathophysiological mechanisms underlying severe mental illnesses like schizophrenia and major depression. Taking a reverse-translational approach, this work utilizes postmortem tissue from subjects with neuropsychiatric disorders and applies a range of molecular and "omic" methods to elucidate disease associated changes in human brain.
1. The glutamate transporter in schizophrenia. Having characterized altered gene expression in splice variants of the glutamate transporter EAAT2 in several different brain regions in schizophrenia, current work is focused on determining the extent and consequences of altered localization of EAAT2 at the ultrastructural level. In addition, applying neurochemical assays will characterize changes in the EAAT2 interactome, or the network of metabolic and structural proteins that support the function of EAAT2 in the brain.
2. Aberrant metabolism of the adenosine system in disease. Adenosine modulates the glutamate and dopamine neurotransmitter systems which are dysregulated in schizophrenia and contribute to the positive, negative and cognitive symptoms of schizophrenia. The metabolic pathways responsible for generating adenosine, a ubiquitous and multifunctional nucleoside that is essential for normal brain function, are significantly dysregulated at the gene level in schizophrenia. We have found that cell-specific (neuronal and astrocytic) pathways that generate adenosine are downregulated, which may contribute to hypofunction of the adenosine system in illness. Ongoing work in the laboratory is examining the protein expression and enzyme activity of adenosine metabolism pathways in schizophrenia.
3. Cell-specific kinome analysis in depression. This project examines cell-specific alterations in kinase activity in prefrontal cortex in depression. A role for dysregulated signal transduction pathways have been implicated in the pathophysiology and treatment of depression. Isolating and enriching cell-populations implicated in disease and examining alterations in kinome activity will enhance our understanding of mechanisms underlying this complex and understudied disorder and potentially lead to the development of new treatments of disease.
Publications:
Sex Differences in DEK Expression in the Anterior Cingulate Cortex and its Association
with Dementia Severity in Schizophrenia. SM O’Donovan, V Ghisays, JL Caldwell, V Haroutunian, A Franco-Villaneuva, L M Privette Vinnedge,
RE McCullumsmith, MB Solomon. (2018) Schizophrenia Research. [Epub ahead of print].
Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia. Sullivan CR, Koene RH, Hasselfeld K, SM O'Donovan, Ramsey A, McCullumsmith RE. (2018) Molecular Psychiatry. [Epub ahead of print].
Cell-subtype-specific changes in adenosine pathways in schizophrenia. SM O'Donovan, Sullivan C, Koene R, Devine E, Hasselfeld K, Moody CL, McCullumsmith RE. (2018) Neuropsychopharmacology 43 (8), 1667-1674.
Defects in bioenergetic coupling in schizophrenia. CR Sullivan, SM O’Donovan, RE McCullumsmith, A Ramsey (2017). Biological Psychiatry 83 (9), 739-750.
The role of glutamate transporters in the pathophysiology of neuropsychiatric disorders. SM O’Donovan, CR Sullivan, RE McCullumsmith (2017). npj Schizophrenia 3 (1), 32.
Contrasting the Role of xCT and GLT-1 Upregulation in the Ability of Ceftriaxone to Attenuate the Cue-Induced Reinstatement of Cocaine Seeking and Normalize AMPA Receptor Subunit Expression AL LaCrosse, SM O'Donovan, MT Sepulveda-Orengo, RE McCullumsmith, KJ Reissner, M Schwendt and LA Knackstedt (2017). Journal of Neuroscience 37 (24), 5809-5821.
Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study. KM Ryan, A Glaviano, SM O'Donovan, E Kolshus, R Dunne, A Kavanagh, A Jelovac, M Noone, GM Tucker, MJ Dunn, DM McLoughlin (2017). Translational Psychiatry 7 (3), e1073.
Abnormalities of signal transduction networks in chronic schizophrenia. JL McGuire, EA Depasquale, AJ Funk, SM O’Donovan, K Hasselfeld, Shruti Marwaha, JH Hammond, V Hartounian, JH Meador-Woodruff, J Meller, RE McCullumsmith (2017). npj Schizophrenia 3 (30).
Shaping plasticity: Alterations in glutamate transporter localization as a pathophysiological mechanism in severe mental illness. RE McCullumsmith, SM O'Donovan, JB Drummond, FS Benesh, M Simmons, R Roberts, T Lauriat, V Haroutunian, JH Meador-Woodruff (2016). Molecular Psychiatry 21 (6), 723.
Cell-specific abnormalities of glutamate transporters in schizophrenia: sick astrocytes and compensating relay neurons? RE McCullumsmith, SM O’Donovan, JB Drummond, FS Benesh, M Simmons, R Roberts, T Lauriat, V Haroutunian, JH Meador-Woodruff (2016). Molecular Psychiatry 21 (6), 823-830.
Glutamate transporter splice variant expression in an enriched pyramidal cell population
in schizophrenia. SM O'Donovan, K Hasselfeld, D Bauer, M Simmons, P Roussos, V Haroutunian, JH Meador-Woodruff,
RE McCullumsmith (2015). Translational Psychiatry 5 (6), e579.
The Effects of Chronic Electroconvulsive Stimulation on the Rodent Hippocampal Proteome.
SM O’Donovan, VS Dalton, MJ Dunn, DM McLoughlin (2015). Current Proteomics 12 (4), 227-235.
The persisting effects of electroconvulsive stimulation on the hippocampal proteome. SM O’Donovan, S O’Mara, MJ Dunn, DM McLoughlin (2014). Brain Research 1593, 106-116.
Acute phase plasma proteins are altered by electroconvulsive stimulation. *A Glaviano, *SM O’Donovan, K Ryan, S O’Mara, MJ Dunn, DM McLoughlin (2014). Journal of Psychopharmacology 28 (12), 1125-1134 *contributed equally to this work.
Effects of brief pulse and ultrabrief pulse electroconvulsive stimulation on rodent brain and behaviour in the corticosterone model of depression. SM O'Donovan, V Dalton, A Harkin, DM McLoughlin (2014). International Journal of Neuropsychopharmacology 17 (9), 1477-1486.
Electroconvulsive stimulation alters levels of BDNF-associated microRNAs. KM Ryan, SM O’Donovan, DM McLoughlin (2013). Neuroscience Letters 549, 125-129.
A comparison of brief pulse and ultrabrief pulse electroconvulsive stimulation on rodent brain and behaviour. SM O'Donovan, M Kennedy, B Guinan, S O'Mara, DM McLoughlin (2012). Progress in Neuro-Psychopharmacology and Biological Psychiatry 37 (1), 147-152.
Facing challenges in Proteomics today and in the coming decade: Report of Roundtable Discussions at the 4th EuPA Scientific Meeting, Portugal, Estoril 2010. J Cox, RMA Heeren, P James, JV Jorrin-Novo, E Kolker, F Levander, N Morrice, P Picotti, PG Righetti, JC Sánchez, CW Turck, R Zubarev, BM Alexandre, FJ Corrales, G Marko-Varga, SM O'Donovan, S O'Neil, J Prechl, T Simões, W Weckwerth, D Penque (2010). Journal of Proteomics 75 (1), 4-17.