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Lorna R. Fiedler

PhD


Postdoctoral Scientist in Cardiovascular Biology

  • Senior Researcher, OxStem Cardio

Life and Death in the Heart - Molecular Mechanisms and Translational Studies

Lorna joined OxStem Cardio in 2017, having previously held a research fellowship position at Duke-NUS Singapore (2015-2016) and completing postdoctoral training at Imperial College London (2009-2014), University College London (UCL, 2008-2009) and Cardiff University College of Medicine, where she also gained her PhD in vascular extracellular matrix biology (2007). Prior to this, she worked in the biotechnology sector for two years (Adprotech, 2001-2003).

Her interest is in understanding the molecular mechanisms of cardiovascular disease and translating this knowledge for clinical use. She works at the interface between basic science and drug discovery, and previously used a target-based approach to develop a novel therapy to suppress cell death in the heart following infarction.

Together with Professors Roger Patient and Paul Riley, as part of OxStem Cardio, she is currently applying phenotype based approaches to identify drugs to regenerate the heart and improve recovery following infarction.

Despite investment in new treatments, cardiovascular conditions continue to have a substantial impact on quality of life, mortality and health resources. The impact of new cardiovascular therapies is hampered by lack of mechanistic understanding of disease, poor clinical translation and drug cardiotoxicity. To address these issues, she has an interest in developing highly translational workflows. These encompass use of human cell based models; induced pluripotent or embryonic stem cell-derived, healthy or from patients. Another approach is to use 3-dimensional models to more closely recapitulate the intact heart, such as engineered human heart tissue (EHT) or living cardiac slices from murine models or teleost fish. More relevant pre-clinical models such as these, along with detailed knowledge of the underlying signalling mechanisms involved in both disease and treatments will provide a firm foundation for progression to the clinical stage. She is also interested in developing models specifically designed to mitigate risk of cardiotoxicity and arrhythmia in clinical trials.

Previous Projects

i) Target based approaches for drug discovery: Validation of the STE20 MAP4 kinase MAP4K4/HGK as a therapeutic target in mitigating cardiomyocyte cell death and development of cardioprotective pharmacological inhibitors - Currently funded by a Wellcome Trust Seeding Drug Discovery Grant (Michael Schneider), manuscript under revision (Cell Stem Cell).

ii) Titin mutations, prevalent in dilated cardiomyopathy, induce hyperactivation of mTOR and metabolic reprogramming rendering the heart susceptible to failure – Published in Nat Genet 2016.

iii) The cardiovascular disease associated nitric oxide inhibitor ADMA inhibits angiogenesis through impaired Rho GTPase signalling - Published in ATVB, Biochem J, Cell Adh Migr.

iv) Decorin, an extracellular matrix component, signals in endothelial cells during angiogenesis, though IGF-1R and alpha2beta1 integrin dependent mechanisms – Published in JBC, Cell Adh Migr

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