Ruoli Chen
- Title
- Lecturer in Clinical Pharmacology
- Location
- Hornbeam 2.28
- Role
- Research theme: Therapeutics
- Contact me
- Office or via email
- Phone
- +44 (0) 1782 733849
- r.chen@keele.ac.uk
Biography
I joined the School of Pharmacy as a Lecturer in Clinical Pharmacology in 2011. My background is medicine and I completed my PhD in clinical physiology at National Heart and Lung Institute, Imperial College London in 2002. I then worked as a postdoctoral research fellow at King’s College London and University of Oxford. My research interests focus on stroke medicine, blood-brain barrier, CSF proteomics and hypoxia-inducible factors.
Research and scholarship
ISTM Research theme: Cell & Molecular Medicine
My current research focuses on three main themes:
- Stroke medicine
- Hypoxia inducible factor (HIF) pathway
- blood brain barrier (BBB)
Current research projects are:
1. Pharmacological accumulation of HIF for neuroprotection in cerebral ischaemia
Ischaemic stroke is the leading cause of adult disability and the third biggest killer in the UK after heart attacks and cancer. Fundamental treatment for ischaemic strokes are reperfusion and neuroprotection. An approach to target entire physiological networks has been proposed to influence a number of targets at one time and thereby simultaneously supressed both ischaemic and reperfusion damage. HIF is a transcription factor that mediates essential homeostatic responses to reduced O2 availability in mammals. HIF1 has been implicated in the neuroprotection induced by hypoxia/ischaemia preconditioning in brains. A number of chemicals inhibiting prolyl hydroxylases (PHDs) can accumulate HIF in cells and could protect tissues/organs from ischaemic injury. We are going to study a number of clinical compounds that inhibit HIF PHDs for their potential neuroprotective properties in both in vitro and in vivo, collaborating with two Oxford groups (with Profs. Alastair Buchan and Chris Schofield, University of Oxford).
2. Stem cell culture in hypoxia
The process of expanding adult stem cells has been proven to be challenging not only from the bioengineering standpoint, but also from the perspective of maintaining stem cell characteristics while avoiding or delaying senescence and genetic instability. It is difficult to recapture the in vivo hypoxia environment in culture, unless maintaining the culture under a hypoxic laminar flow hood combined with a hypoxic incubator. It has been proposed that hypoxia-mimetic agents could provide a useful tool to precisely control oxygen levels in stem cell culture to maintain their native characteristics. Hypoxia-mimetic agents “artificially” induce hypoxia through blocking the degradation of HIF-1a via prolyl hydroxylase (PHD) inhibition. We are going to study some novel, selective, small molecule inhibitors of PHDs on stem cell culture to identify key gene expression and signal pathways for optimal stem cell expanding in vitro. The outcome will be informed to chemists to synthesize highly potent, more specific PHD inhibitors (with Dr Nicholas Forsyth, Keele University and Prof. Chris Schofield, University of Oxford).
3. Blood brain barrier integrity and function in ageing and in neurodegenerative diseases
Hypoxia/ischemic preconditioning is considered the next most powerful experimental neuroprotective strategy after hypothermia. HIF is of central importance in the response to hypoxia/ischaemia, and is essential for cerebral ischaemia tolerance induced by hypoxic preconditioning. Ischaemic stroke firstly affects brain endothelial cells, which form the BBB. BBB function and integrity during ischaemic stroke contribute substantially to neuropreotection and the outcomes of stroke patients. We shall investigate effects of brief exposure of BBB to hypoxia / PHD inhibition on BBB integrity and function during subsequent prolonged ischaemia (OGD). This study will identify novel therapeutic targets to prevent and treat ischaemic stroke (with Prof. Christine Roffe, Keele University and Dr Jane Preston, King’s College London).
Teaching
I teach elements of the undergraduate curriculum for the Keele University MPharm in the School of Pharmacy.
Selected Publications
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2020. Characterizing Ischaemic Tolerance in Rat Pheochromocytoma (PC12) Cells and Primary Rat Neurons. Neuroscience, vol. 453, 17-31. link> doi> full text>
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2021. Hypoxia in Alzheimer's disease: effects of hypoxia inducible factors. Neural Regen Res, vol. 16(2), 310-311. link> doi> full text>
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2020. Post-Ischaemic Immunological Response in the Brain: Targeting Microglia in Ischaemic Stroke Therapy. Brain Sci, vol. 10(3). link> doi> full text>
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2020. Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors induce autophagy and have a protective effect in an in-vitro ischaemia model. Sci Rep, vol. 10(1), 1597. link> doi> full text>
Full Publications List show
Journal Articles
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2020. Characterizing Ischaemic Tolerance in Rat Pheochromocytoma (PC12) Cells and Primary Rat Neurons. Neuroscience, vol. 453, 17-31. link> doi> full text>
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2021. Hypoxia in Alzheimer's disease: effects of hypoxia inducible factors. Neural Regen Res, vol. 16(2), 310-311. link> doi> full text>
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2020. Post-Ischaemic Immunological Response in the Brain: Targeting Microglia in Ischaemic Stroke Therapy. Brain Sci, vol. 10(3). link> doi> full text>
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2020. Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors induce autophagy and have a protective effect in an in-vitro ischaemia model. Sci Rep, vol. 10(1), 1597. link> doi> full text>
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2019. Editorial: The Development of New Classes of Hypoxia Mimetic Agents for Clinical Use. Front Cell Dev Biol, vol. 7, 120. link> doi> full text>
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2018. Reactive Oxygen Species Formation in the Brain at Different Oxygen Levels: The Role of Hypoxia Inducible Factors. Front Cell Dev Biol, vol. 6, 132. link> doi> full text>
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2018. Proteomic analysis of age-related changes in ovine cerebrospinal fluid. Exp Gerontol, vol. 108, 181-188. link> doi> full text>
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2017. Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral edema in mice. Brain Behav Immun, vol. 64, 266-275. link> doi> full text>
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2016. EFFECTS OF TRANSTHYRETIN ON THYROXINE AND β-AMYLOID REMOVAL FROM CEREBROSPINAL FLUID IN MICE. Clinical and Experimental Pharmacology and Physiology. doi> full text>
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2016. Effects of transthyretin on thyroxine and β-amyloid removal from cerebrospinal fluid in mice. Clinical and experimental pharmacology & physiology. doi> full text>
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2015. Socioeconomic deprivation and survival after stroke in China: a systematic literature review and a new population-based cohort study. BMJ Open, vol. 5(1), e005688. link> doi> full text>
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2015. Socioeconomic deprivation and survival after stroke in China: a systematic literature review and a new population-based cohort study. BMJ Open, vol. 5(1). doi> full text>
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2014. Changes of synovial fluid protein concentrations in Supra-Patellar Bursitis patients after the injection of different molecular weight hyaluronic acids. Experimental Gerontology, vol. 52, 30-35. doi>
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2014. HIF prolyl hydroxylase inhibition prior to transient focal cerebral ischaemia is neuroprotective in mice. J Neurochem, vol. 131, 177-189. doi>
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2013. Stem cell therapy for ischaemic stroke: translation from preclinical studies to clinical treatment. CNS Neurol Disord Drug Targets, vol. 12(2), 209-219. link> doi> full text>
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2013. Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy. doi>
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2012. Changes in kinetic of amino acids uptake at the ageing ovine blood-cerebrospinal fluid barrier. Neurobiology of Aging, 121-133.
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2012. Roles of Individual Prolyl-4-Hydroxylases Subtypes (PHD1-3) in Cerebral Ischaemia: Insights from Genetically Modified Mice. Journal of Physiology, 4079-4091.
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2010. Elevation of CSF albumin in old sheep : relations to CSF turnover and albumin extraction at blood CSF barrier. Journal of Neurochemistry, 1230-1239.
Other
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Conference paper.
PhD Students
I welcome applications from students who wish to undertake PhD or MPhil postgraduate studies in my team. Interested students can contact me directly on r.chen@keele.ac.uk to discuss potential projects as well as the application process for these degrees.
My current research interests are as indicated on the "Research and Scholarship" tab. Currently, we are studying a novel class of small molecule HIF prolyl hydroxylase inhibitors for neuroprotection in ischaemic stroke both in vitro and in vivo.
My team works closely with those of other investigators interested in neuroscience as part of Molecular Medicine providing a stimulating collegiate environment for postgraduate research students, regular contact with your supervisory team and access to modern research facilities.
