Chris Denning

Biography

Chris Denning is a Professor in, and Head of Department of, Stem Cell Biology. He leads the University's Research Priority Area in Regenerative Medicine & Stem Cells. His lab's interests are in cardiomyocyte (heart cell) differentiation of human pluripotent stem cells (hPSCs: human embryonic stem cells [hESCs] and human induced pluripotent stem cells [hiPSCs]) for use in drug screening and in production of new in vitro models of genetic-based cardiovascular disease. Broadly, the lab works in 3 main areas: 1) Disease modelling. Enabled via human induced pluripotent stem cells with or without additional manipulation by nuclease-mediated gene targeting technologies (including Cas9/CRISPR). As examples, the lab investigate diseases associated with defects in electrophysiology (e.g. long QT syndrome, CPVT, myotonic dystrophy), structure (e.g. myosin heavy chains, alpha-actin), survival (e.g. DMD) and signalling (e.g. b-adrenoceptors, GRK5). We also use gene targeting for knockout and knockin studies. 2) Platforms for cardiotoxicity evaluation. As an example, Chris leads the multinational CRACK-IT consortium, which aims to improve stem cell-cardiomyocyte models in the predictivity of drug-induced cardiotoxicity. The consortium includes 3 additional academic groups (Christine Mummery, Holland; Thomas Eschenhagen, Germany; Godfrey Smith, Scotland), 2 biotechs (ClydeBiosciences; Pluriomics) and Pharma (GlaxoSmithKline). This is facilitated by high throughput phenotyping platforms to assess changes in electrophysiology, calcium and contractility. 3) Automation and interdisciplinary approaches. Over the last 5 years, Chris has developed a £2M automation and phenotyping suite. This is embedded in a world-class stem cell culture facility, which includes 25 class II cell culture cabinets. This enables projects such as screening of an 83,000 compound library to find chemistries that improve cardiomyocyte maturity, as well as development of stem cell quality metrics. High throughput approaches have also enabled screening of polymer microarrays to identify chemistries that can alter stem cell and cardiomyocyte fate. Appointments in brief: PhD in Cancer Gene Therapy, Glasgow, 1997; Postdoc: Institute for Stem Cell Research, Edinburgh 1997-98; Postdoc: Roslin Institute 1998-2001; Fellow (2001), Lecturer (2006), Reader (2008), Professor (2011) in Stem Cell Biology; from 2014 Head of Department of Stem Cell Biology, University of Nottingham Education and appointments First class hons in Biochemistry with Molecular Biology, University of Leeds 1994; PhD in Cancer Gene Therapy at Beatson Institute for Cancer Research, University of Glasgow, 1997; Postdoctoral Research Fellow - gene targeting in mouse ES cells, Institute for Stem Cell Research, University of Edinburgh, 1997-1998; Postdoctoral Research Fellow - gene targeting / cloning in somatic cells, Roslin Institute 1998-2001; Principal Investigator, University of Nottingham, 2001-2003; Medical Research Council Fellow, University of Nottingham, 2003-2006; Lecturer, University of Nottingham, 2006-2008; Reader, University of Nottingham 2008-2011; Professor in Stem Cell Biology, University of Nottingham 2011-

Research Interest

Chris' interests are in cardiomyocyte (heart cell) differentiation of human pluripotent stem cells (hPSCs: human embryonic stem cells [hESCs] and human induced pluripotent stem cells [hiPSCs]) for use in drug screening and in production of new in vitro models of genetic-based cardiovascular disease. Broadly, the lab works in 3 main areas: 1) Disease modelling. Enabled via human induced pluripotent stem cells with or without additional manipulation by nuclease-mediated gene targeting technologies (including Cas9/CRISPR). As examples, the lab investigate diseases associated with defects in electrophysiology (e.g. long QT syndrome, CPVT, myotonic dystrophy), structure (e.g. myosin heavy chains, alpha-actin), survival (e.g. DMD) and signalling (e.g. b-adrenoceptors, GRK5). We also use gene targeting for knockout and knockin studies.