Stipendiary Lecturer; BHF CRE Intermediate Transition Research Fellow
Some chemotherapeutic agents, such as doxorubicin, have severe cardiotoxic side effects, which can lead to congestive heart failure in 5% of patients.
There are currently no imaging techniques available to detect patients before the onset of functional decline and there are no specific cardio-protective drugs. My research focuses on both the early detection of cardiotoxicity using the novel metabolic imaging technique, hyperpolarized magnetic resonance imaging (MRI) and the repurposing of existing drugs that target cardiac metabolism as potential cardio-protective therapy.
Before I came to the UK I trained as a vet at the Freie Universitaet Berlin (Germany). I then undertook an MRes in “In Vivo Imaging in Biology and Medicine” and a PhD in Biochemistry at the University of Cambridge. During my PhD in Prof Kevin Brindle’s laboratory I used hyperpolarized MRI to assess tumour metabolism and redox state in mouse models of cancer. I was then awarded a British Heart Foundation (BHF) Immediate Postdoctoral Basic Science Research Fellowship to move to the Department of Physiology Anatomy and Genetics (DPAG) at the University of Oxford. During my time in Prof Damian Tyler’s lab at DPAG I established a clinically-relevant rat model of doxorubicin-induced cardiotoxicity and found that hyperpolarized MRI can detect early changes in cardiac mitochondrial metabolism that precede functional decline. I am now in the process of testing existing drugs that boost mitochondrial metabolism and have some early encouraging data that shows prevention of functional decline with this approach in rats treated wit doxorubicin.
In addition to my role as Career Development Fellow at the Department of Pharmacology, I am also the Isobel Laing Career Development Fellow in Medical Sciences at Oriel college. This involves tutorial teaching in metabolism for first year Medical and Biomedical Sciences students. I am furthermore a Stipendiary Lecturer in Medicine at Somerville College (since 2017), where I conduct tutorials in the ‘Organisation of the Body’ course for first year medics, for whom I am also personal tutor. In addition I offer FHS tutorials in cancer metabolism and I act as College Adviser to graduate students in Medical Sciences. In the past I was a Lecturer in Metabolism at Corpus Christi College (2016-2020). I am passionate about disseminating research to the wider public and have thus taken part in outreach events such as ‘Pint of Science’ and ‘FameLab’ as well as events organised by the BHF and Somerville College.
‘L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI’
Savic D. et al, (2021), Metabolites, 11
‘Hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart
SAVIC D. et al, (2021), NMR in Biomedicine
‘Rapid, $B_1$-insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux’
Miller JJ. et al, (2020), Magnetic Resonance in Medicine
‘Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI’
Timm KN. et al, (2020), Commun Biol, 3
‘Nicotinic acid receptor agonists impair myocardial contractility by energy starvation’
Watson WD. et al, (2020), FASEB J
‘Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR’
Marco-Rius I. et al, (2020), MAGMA
‘A 3D hybrid-shot spiral sequence for hyperpolarized 13 C imaging.’
Tyler A. et al, (2020), Magn Reson Med
‘A 3D hybrid-shot spiral sequence for hyperpolarized 13C imaging’
TYLER D. et al, (2020), Magnetic Resonance in Medicine
‘Rescue of myocardial energetic dysfunction in diabetes through the correction of mitochondrial hyperacetylation by honokiol.’
Kerr M. et al, (2020), JCI Insight, 5
‘The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity’
Timm KN. and Tyler DJ., (2020), Cardiovasc Drugs Ther, 34, 255 – 269