Stem Cells & Regenerative Medicine at King’s

The Centre for Stem Cells & Regenerative Medicine at King’s College London is located on the Guy’s Hospital Campus in central London. It acts as a nucleus for a vibrant research community spanning the entire university and the NHS Foundation Trusts of King’s Health Partners (KHP) Academic Health Sciences Centre. The goal of the Centre is to bring together researchers with diverse skill sets and a common interest in elucidating the extrinsic and intrinsic signals that regulate stem cell behaviour. To facilitate collaborations within King’s and with external partners, we have opened a ‘Stem Cell Hotel’ where researchers can access specialist equipment and technical support to study stem cell behaviour at single cell resolution. We also host and run Stem Cells @ Lunch seminars.

This booklet lists many of the investigators within King’s and KHP whose interests include stem cells and regenerative medicine. As you can see, our research portfolio is rich and diverse, ranging from health economics and research ethics, through studies of asymmetric cell division, to clinical trials of autologous and allogeneic cell therapies. We benefit from interactions with scientists across London, including the and Innovate UK’s Cell and Gene Therapy Catapult at Guy’s Hospital.

I hope you will enjoy reading about what we have to offer at King’s, and that you will be inspired to join us, whether by attending seminars or initiating exciting collaborations.

With best wishes,

Fiona M Watt, Centre Director 15th Nov 2018

Centre for Stem Cells & Regenerative Medicine | 1 Researchers at King’s benefit from superb core facilities that underpin a diverse range of laboratory-based and clinical research activities.

Recapitulating embryonic development in vitro using Mouse whole skin showing hair follicles (red) and human induced pluripotent stem cells. blood vessels (green).

2 | Centre for Stem Cells & Regenerative Medicine KCL imaging facilities support the full spectrum of analysis, from super-resolution light microscopy of single cells to PET/CT scanners for clinical imaging. We host a Nikon Imaging Centre, which is a core facility for light microscopy developed as a partnership between King’s and Nikon Instruments UK. The Nikon Centre complements the Centre for Ultrastructural Imaging, which provides access to a full range of electron microscopy equipment.

Our research environment is enriched by expertise in generating human pluripotent and tissue stem cells. We have equipment for single cell gene expression profiling, high content imaging and protein production.

King’s Health Partners (KHP) houses two NIHR Biomedical Research Centres (BRC) and a Dementia Biomedical Research Unit (BRU). Biomedical Research Centres and Units drive progress in translational research in biomedicine into NHS practice. BRC core facilities include flow cytometry, genomics and bioinformatics.

The University has state-of-the art GMP facilities for gene and cell therapy, and is one of the few centres in the UK engaged in cell-based clinical trials.

Centre for Stem Cells & Regenerative Medicine | 3 Background image: Human dermal fibroblasts from a 64 year old donor.

PhD students Chloe Hurling, Arsham Gharamani Postdoctoral research associate Dr Christina and Victor Negri discussing data. Philippeos stains her sections for imaging.

4 | Centre for Stem Cells & Regenerative Medicine International Seminar Series Journal Club We host a series of international seminars Our journal club is run by Davide Danovi by leading researchers in the stem cell Alice Vickers and Chris Lambert. Generous community. Our inaugural speaker was support ensures that there is always plenty Kevin Eggan. Subsequent speakers have of pizza at these events. We meet every included: Irving Weissman (Stanford), week to talk about exciting developments Rusty Gage (Salk), Konrad Hochedlinger and recent publications in the field of stem (Harvard), Lee Rubin (Harvard), Marianne cell research and beyond. Bronner (Caltech), Ken-ichiro Kamei (Kyoto), Jason Burdick (UPenn), Gregg Sando (Cell Medica), Amy Wagers Wellcome Trust 4-year PhD Programme (Harvard), Ed Boyden (MIT), Jody This PhD programme is training a new Rosenblatt (University of Utah) and generation of researchers in regenerative Kathleen Green (Northwestern University). medicine. PhD supervisors have expertise in a wide spectrum of research areas related to regenerative medicine. Collectively, Stem Cells @ Lunch they provide knowledge in diseases of This series of informal seminars was set up unmet clinical need, in innate and adaptive by Sam Woodhouse and Christine Weber and immunity, in organ transplantation and is now run by PostDocs at the Centre. There clinical trials of cell and gene therapies. are two seminars each month, each consisting Supervisors also have scientific expertise of two 20 minute talks, with discussion. The in endogenous tissue repair, and knowledge emphasis is on sharing unpublished research, of bioengineering, disease modelling, drug fostering collaborations and sharing reagents screens and cell tracking. This programme and expertise. equips students to further translate the Presentations by King’s scientists are cell sciences into the clinic. As part of the interspersed with outside speakers. We also programme we host events such as Master discuss topics of general interest, such as Classes and movie nights that are open to all. publishing strategies, preparing applications for career development fellowships and communicating science to the public. Open Innovation The speakers from Stem Cells @ Lunch We actively seek to innovate new technologies also take part in our podcast Stem Cells @ and have strong links with industrial Lunch Digested. These podcasts feature partners: Perkin Elmer has embedded a short interviews with our speakers, in which facility manager within the Stem Cell Hotel they discuss their current research interests who is available to provide training and and their hopes for the future of stem cell support to users; Orchard Therapeutics, research. You can download this podcast a gene therapy company, has chosen the on iTunes. Centre for its UK research and development laboratories; Unilever funds several research projects which benefit from the established capabilities at the Centre.

Centre for Stem Cells & Regenerative Medicine | 5 Background image: Students embroider stem cell trajectories at a public outreach event

Dr Rocio Sancho and PhD student Ana-Maria Cujba discuss A student from a local school learns cell therapies with a visitor at Cancer Survivors Day how extract DNA from strawberries

6 | Centre for Stem Cells & Regenerative Medicine Public Engagement coordinating visits from schools across Patient and public involvement (PPI) London and collaborating with science in research refers to the active partnership outreach initiatives including The London between patients, members of the public International Youth Forum, King’s STARS and researchers. Patients and the public and Native Scientist. can play an important role in contributing Our scientists also create accessible to research as advisers and potentially also online content, including a weekly as co-researchers. They can, for example, podcast series explaining current stem provide insights based on direct experience cell research in an understandable way. of a disease, and they can provide valuable They publish regular blog articles spanning education to early career researchers. a wide variety of topics, and manage a very At the CSCRM we have an active public active social media presence to share our engagement program. Our researchers, research updates and publicised events. whether senior investigators, postdocs, PhD students or research assistants enjoy, and are good at, explaining their research to the public. Along with our research staff, we also have a full-time Public Engagement Officer, Jessica Sells. Jessica is dedicated to bringing awareness of our research to the public, and where possible involving them in our research. She coordinates staff and student activities in a wide variety of public engagement events and platforms. Our researchers regularly take part in public events, including the very popular Pint of Science festival, in which members of the public come to listen to current science projects in a casual pub setting. Students have spoken at music festivals such as Green Man explaining their research on brain development using mini “Really want to do stuff in cell science now robots and fruit fly larvae. Staff have used as it is so cool and you can learn so much” embroidery and origami to explain stem No name, 11, Streatham cell science to patients and visitors of Guy’s and St Thomas’ Hospital at International “At first thought stem cells were boring Clinical Trials Day and Cancer Survivor but now think they’re awesome” Day Events. These are just some of the Connie, 11, Lambeth events that attract hundreds of visitors. We are passionate about connecting with Enjoyed the stem cell embroidery “because our audience in diverse ways, including I developed my stitching and learned about collaborations with fashion brands to the structure of cells” produce stem cell embroidery workshops, Melvina, 15, Deptford and teaming up with multimedia artists to generate exciting science art content for Enjoyed stem cell embroidery “because exhibitions at the Science Gallery London. it was very inclusive and fun” We host a wide range of interactive Emamanuella, 15, Clapham educational activities at our Centre,

Centre for Stem Cells & Regenerative Medicine | 7 Simon Broad selects stem cells stored in liquid nitrogen

8 | Centre for Stem Cells & Regenerative Medicine Dr Thomas Iskratsch �������������������������������� 34 Professor Peter Jones ����������������������������� 35 Dr Aileen King ������������������������������������������ 36 Dr Robert Knight ��������������������������������������37 Dr Ivo Lieberam ��������������������������������������� 38 Dr Karen Liu ��������������������������������������������� 39 Dr Alexis Lomakin ������������������������������������ 40 Professor Giovanna Lombardi ������������������41 Dr Magnus Lynch �������������������������������������� 42 Dr John Maher FRCPath �������������������������� 43 Professor Michael Malim �������������������������� 44 Professor Manuel Mayr ��������������������������� 45 Professor John McGrath �������������������������� 46 Dr Isabelle Miletich �����������������������������������47 Mr Bijan Modarai FRCS ���������������������������� 48 Professor Ghulam Mufti FRCP ����������������� 49 Dr Joana F Neves ������������������������������������� 50 Dr Aamir Ahmed ���������������������������������������10 Professor Antonio Pagliuca �����������������������51 Professor Stephanie Amiel ���������������������� 11 Professor Carmine Pariante ������������������� 52 Dr Cynthia Lilian Andoniadou ��������������������12 Professor Lucilla Poston Dr Michael Antoniou ����������������������������������13 FMedSci FRCOG ����������������������������������� 53 Dr Linda Barber ����������������������������������������14 Dr S Tamir Rashid ������������������������������������ 54 Dr M Albert Basson ����������������������������������15 Professor Steven Sacks ����������������������������55 Professor Philip Blower ����������������������������16 Professor Brian Salter ���������������������������� 56 Professor Elizabeth Bradbury �������������������17 Dr Rocio Sancho ���������������������������������������57 Professor Juan Burrone ���������������������������18 Professor Rosamund Scott ����������������������58 Dr Ciro Chiappini ��������������������������������������19 Professor Paul Sharpe ����������������������������� 59 Dr Attila Csikász-Nagy ����������������������������� 20 Professor Christopher E Shaw Dr Davide Danovi ��������������������������������������21 FRCP FMedSci �������������������������������������� 60 Professor Francesco Dazzi ���������������������� 22 Dr Tanya Shaw ������������������������������������������61 Professor Anil Dhawan ���������������������������� 23 Professor Chi Wai ‘Eric’ So ���������������������� 62 Professor Lucy (Luciana) Di Silvio ����������� 24 Dr Rita Sousa-Nunes �������������������������������� 63 Dr Georgina Ellison-Hughes ��������������������� 25 Dr Francesca Spagnoli ����������������������������� 64 Dr Gerald Finnerty FRCP ������������������������� 26 Professor Karen Steel ������������������������������ 65 Dr Massimo Garriboli Professor Andrea Streit �������������������������� 66 FEBPS FRCS(Eng) ���������������������������������27 Dr Sandrine Thuret �����������������������������������67 Dr Eileen Gentleman �������������������������������� 28 Professor Abigail Tucker �������������������������� 68 Professor Agi Grigoriadis ������������������������ 29 Dr Alessandra Vigilante ���������������������������� 69 Dr Pierre Guermonprez ��������������������������� 30 Dr Fiona Wardle ����������������������������������������70 Dr Shukry J Habib �������������������������������������31 Professor Fiona M Watt FRS FMedSci �������71 Professor Stephen Harridge ������������������� 32 Professor Qingbo Xu ���������������������������������72 Dr Dusko Ilic ��������������������������������������������� 33 Professor Peter Zammit ���������������������������73

Centre for Stem Cells & Regenerative Medicine | 9 Dr Aamir Ahmed Head of Stem Cell and Prostate Cancer Group BSc (Hons., University of Karachi, 1985); MSc (University of Karachi, 1986); PhD (University of Dundee, October 1987 – February 1991)

Research interests I am interested in discovering how cells respond to their environment, particularly to various signals (proteins and other molecules) that regulate cell division and how ‘controlled’ cell proliferation becomes ‘uncontrolled’ and malignant. I am interested, particularly, in the Wnt signaling network, a critical signaling pathway during development and in disease. The focus of my research is the role Wnt signalling plays in prostate stem cells and prostate cancer. We are investigating how cell electrical activity may regulate this pathway and how this property could be harnessed to develop anti-cancer therapies. A wide range of molecular biological, biochemical, histochemical, live cell imaging and high throughput (genomic, proteomic, electrophysiological and tissue imaging) techniques are used to address fundamental questions regarding Wnt signalling and to translate this knowledge into better therapies and quantitative biomarkers of cancer.

Publications • Arthurs C, Murtaza B, Thomson C, Dickens K, Henrique R, Patel H, Beltran M, Millar M, Thrasivoulou C and Ahmed A. Expression of ribosomal proteins in normal and cancerous human prostate tissue. PLoS ONE. 2017;12(10):e0186047. • Petrou T, Olsen H, Thrasivoulou C, Masters J, Ashmore J and Ahmed A. Intracellular calcium mobilization in response to ion channel regulators via a calcium induced calcium release mechanism. J Pharm Exp Therap. 2017;360:378 –387. • Thrasivoulou C, Millar M, Ahmed A. Activation of intracellular calcium by multiple Wnt ligands and translocation of ß-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/ ßcatenin pathways. J Biol Chem. 2013;288:35651-35659.

10 | Centre for Stem Cells & Regenerative Medicine Professor Stephanie Amiel RD Lawrence Professor of Diabetic Medicine Head of Diabetes & Nutritional Sciences Division MD; PhD

Research interests My research interests include hypoglycemia in diabetes, metabolic neuroimaging, brain insulin sensitivity/resistance, and central responses to eating. My work on the aetiopathogenesis of hypoglycaemia unawareness in Type 1 diabetes is currently focused on pharmacological manipulation of cognitive function; investigation of new technologies in hypoglycaemia avoidance during insulin therapy and the use of neuroimaging to investigate abnormalities in cortical function and counterregulation to hypoglycaemia. The techniques developed to investigate regional brain activation and metabolism in hypoglycaemia are now being applied to the wider issues of brain metabolism and function (including glucose sensing) in other disease states. Working with colleagues in Liver Transplantation, I provide a human islet isolation facility to support an active clinical islet transplant programme for patients with Type 1 diabetes and intractable hypoglycaemia. The programme is also active in research aimed at developing islet surrogates from stem cells and islet cells from exocrine pancreas.

Publications • Dunn JT, Choudhary P, Teh MM, Macdonald I, Hunt KF, Marsden PK, Amiel SA. The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes. Diabetologia. 2018;61:1676–1687. • Crosby-Nwaobi RR, Sivaprasad S, Amiel S, Forbes A. The relationship between diabetic retinopathy and cognitive impairment. Diabetes Care. 2013;36(10):3177-86. • Choudhary, P, Huang, GC, Amiel, S & 20 others. Attainment of metabolic goals in the integrated UK islet transplant program with locally isolated and transported preparations. Am J Transpl. 2013;13(12)3236-43.

Centre for Stem Cells & Regenerative Medicine | 11 Dr Cynthia Lilian Andoniadou Lecturer in Stem Cell Biology BSc (Hons) (Queen Mary ); PhD (National Institute for Medical Research / University College London); PGCAPHE (KCL)

Research interests My research aims to understand the basic biology controlling the regulation of the pituitary stem cell compartment. The pituitary is a central regulator of physiological processes. We have shown that stem cells of this organ are capable of generating new hormone – producing cells throughout life and when deregulated can lead to diseases such as hypopituitarism and tumours. The mechanisms that control the stem cell pool and organ homeostasis are poorly understood. We are studying the signals regulating these processes in mouse with the ultimate goal of safer and better approaches for the treatment of human conditions.

Publications • Mario Gonzalez-Meljem J, Haston S, Carreno G, Apps JR, Pozzi S, Stache C, Kaushal G, Virasami A, Panousopoulos L, Neda Mousavy-Gharavy S, Guerrero A, Rashid M, Jani N, Goding CR, Jacques TS, Adams DJ, Gil J, Andoniadou CL, Martinez-Barbera JP. Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma. Nat Commun. 2017;28;8(1):1819. • Haston S, Pozzi S, Carreno G, Manshaei S, Panousopoulos L, Gonzalez-Meljem JM, Apps JR, Virasami A, Thavaraj S, Gutteridge A, Forshew T, Marais R, Brandner S, Jacques TS, Andoniadou CL, Martinez-Barbera JP. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development. 2017;15;144(12):2141-2152. • Andoniadou CL, Matsushima D, Mousavy Gharavy SN, Signore M, Mackintosh AI, Schaeffer M, Gaston-Massuet C, Mollard P, Jacques TS, LeTissier P, Dattani MT, Pevny LH and Martinez- Barbera JP. Sox2+ stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell. 2013;13(4):433-45.

12 | Centre for Stem Cells & Regenerative Medicine Dr Michael Antoniou Reader in Molecular Genetics PhD

Research interests My interests are characterization of tissue-specific locus control regions (LCRs) and ubiquitous chromatin opening elements (UCOEs) that can bring about long-range remodeling of chromatin. I am exploring their potential use in gene therapy especially lentiviral vectors, generation of animal models of human disease and other biotechnology applications. My principle focus is on exploiting UCOEs that have provided unprecedented stability and cell-to-cell reproducibility of expression within adult, embryonic and induced pluripotent stem cells and their differentiated progeny.

Publications • Neville JJ, Orlando J, Mann K, McCloskey B, Antoniou MN. Ubiquitous Chromatin-Opening Elements (UCOEs): Applications in biomanufacturing and gene therapy. Biotechnol Adv. 2017;35(5):557-564. • Dighe N, Khoury M, Mattar C, Chong M, Choolani M, Chen J, Antoniou MN and Chan JK. Long-Term reproducible expression in human fetal liver hematopoietic stem cells with a UCOE- based lentiviral vector. PLoS ONE. 2014;9(8):e104805. • Pfaff N, Lachmann N, Ackermann M, Kohlscheen S, Brendel C, Maetzig T, Niemann H, Antoniou MN, Grez M, Schambach A, Cantz T, Moritz T. A ubiquitous chromatin opening element (UCOE) prevents transgene silencing in pluripotent stem cells and their differentiated progeny. Stem Cells. 2013;31:488-499.

Centre for Stem Cells & Regenerative Medicine | 13 Dr Linda Barber Senior Lecturer PhD

Research interests My research interests are the study of immune dysfunction in leukaemia and recovery of the immune system after allogeneic haematopoietic stem cell transplantation. Immune signatures indicative of beneficial and detrimental clinical courses are identified by comprehensive phenotypic and functional studies of immunity in patients. The goal is improved monitoring to facilitate rapid and tailored treatment regimens and to develop novel specific immunotherapeutic strategies.

Publications • Grimaldi F, Potter V, Perez-Abellan P, Veluchamy JP, Atif M, Grain R, Sen M, Best S, Lea N, Rice C Pagliuca A, Mufti1 GJ, Marsh JCW, Barber LD. Mixed T-cell chimerism after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia using an alemtuzumab-containing regimen is shaped by persistence of recipient CD8 T cells. Biol Blood Marrow Transplant. 2017;23:293-299. • Madrigal JA, Barber LD. Matching inside and outside the HLA molecule in allogeneic hematopoietic stem cell transplantation. Haematologica. 2016;101:1131-1132. • Tye GJ, Ioannou K, Amofah E, Quartey-Papafio R, Westrop SJ, Krishnamurthy P, Noble A, Harrison PM, Gaensler KML, Barber LD*, Farzaneh F*. *equal contributions. The combined molecular adjuvant CASAC enhances the CD8+ T cell response to a tumour-associated self-antigen in aged, immunosenescent mice. Immunity & Ageing. 2015;2:6.

14 | Centre for Stem Cells & Regenerative Medicine Dr M Albert Basson Reader in Developmental and Stem Cell Biology BSc (Hons) (1990); MSc (1992); PhD (1996)

Research interests My group is interested in the mechanisms that maintain cell signalling and gene expression at physiological levels during embryonic and postnatal development and within adult stem cells. We have uncovered key mechanisms that regulate FGF signalling during development. Previous work in collaboration with the Brack laboratory at MGH (Boston) has implicated the deregulation of FGF2 expression in the adult muscle stem cell niche as playing a role in muscle stem cell decline during ageing. Current work is focused on elucidating the role(s) and mechanism of action of chromatin remodelling factors of the CHD family in neural development, stem cell function and autism. In addition, we are interested in understanding the interaction between genes implicated in autism and non-genetic (environmental and epigenetic) factors. In vivo mouse models, in vitro embryonic stem cell systems and genomic and biochemical approaches are employed. iPS cells generated from patients with autism will be particularly useful in exploring gene-environment interactions in the aetiology of autism.

Publications • Whittaker DE, Riegman KLH, Kasah S, Mohan C, Yu T, Pijuan Sala B, Hebaishi H, Caruos A, Marques AC, Michetti C, Sanz Smachetti ME, Shah A, Sabbioni M, Kulhanci O, Tee WW, Reinberg D, Scattoni ML, Volk H, McGonnell I, Wardle F, Fernandes C, Basson MA. The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression. J Clin Invest. 2017;1;127(3):874- 887. • Jones KM, Saric N, Scambler PJ & Basson MA. CHD7 maintains neural stem cell quiescence and prevents premature stem cell depletion in the adult hippocampus. Stem Cells. 2015;33:196-210. • Chakkalakal J, Jones K, Basson MA & Brack AS. The aged niche disrupts muscle stem cell quiescence. Nature. 2012;490:355-360.

Centre for Stem Cells & Regenerative Medicine | 15 Professor Philip Blower Professor of Imaging Chemistry BA 1981; Dphil 1984; Cchem FRSC.

Research interests My research focuses on designing contrast agents for medical imaging, using positron emission tomography (PET), single photon emission tomography, magnetic resonance imaging (MRI) and optical imaging to detect disease and measure response to therapy. These include cell tracking methods, combining direct radiolabelling methods and reporter gene engineering, and development of specific radiotracers for these reporter genes, enabling cell tracking in vivo over days to years. Our multidisciplinary team of academics, including chemists, radiochemists, molecular biologists and radiobiologists contributes expertise in all disciplines required to develop these technologies from bench to bedside. We have developed the first long half life PET tracer for cell tracking (89Zr-oxine), cancer models expressing reporter genes including the human sodium iodide symporter (hNIS), and the first 18F-labelled tracers for imaging hNIS- expressing cells. We have developed PET imaging agents for other targets such as the prostate specific membrane antigen, and a range of nanoparticulate multimodality contrast agents.

Publications • Khoshnevisan A, Chuamsaamarkkee K, Boudjemeline M, Jackson A, Smith GE, Gee AD, Fruhwirth GO, Blower PJ. 18F-Fluorosulfate for PET imaging of the sodium/iodide symporter: synthesis and biological evaluation in vitro and in vivo. J Nucl Med. 2017;58(1)156-161. • Charoenphun P, Meszaros LK, Chuamsaamarkkee K, Sharif- Paghaleh E, Ballinger JR, Ferris TJ, Went MJ, Mullen GED, Blower PJ. [89Zr]-Zr(oxinate)4 for long term in vivo cell tracking by positron emission tomography. Eur J Nucl Med Mol Imaging. 2014;42:278-287. • Fruhwirth GO, Diocou S, Blower PJ, Ng T, Mullen GE. A whole-body dual-modality radionuclide optical strategy for preclinical imaging of metastasis and heterogeneous treatment response in different microenvironments. J Nucl Med. 2014;55:686-694.

16 | Centre for Stem Cells & Regenerative Medicine Professor Elizabeth Bradbury Professor of Regenerative Medicine & Neuroplasticity and MRC Senior Non-Clinical Fellow BA; MSc; PhD

Research interests My major research interests are focused on understanding processes of injury and repair and developing therapies to restore function following central nervous system trauma, with a particular interest in glial scarring, extracellular matrix modification and neuroplasticity after spinal cord injury. Current projects include novel gene therapy approaches to target molecules in injury scar tissue that block nerve repair and regeneration; neurorehabilitative techniques to restore upper limb and hand function following spinal cord injury; proteomics and systems wide approaches to identify novel targets and biomarkers for spinal cord injury and transgenic methods to understand spontaneous repair and remyelination. We use a range of techniques from molecular and cellular biology to functional and anatomical assessments in clinically relevant injury models in vivo. We have a wide network of collaborators ranging from viral vector, genetic engineering and organic chemistry labs (The Netherlands; Cambridge; Caltech) to physiology, imaging and bioinformatics (King’s; Oxford; Switzerland) to clinicians and spinal surgeons conducting clinical trials in spinal injured patients (Miami Project to Cure Paralysis; the London Spinal Cord Injury Centre, Stanmore), making our research at the forefront of translational regenerative medicine.

Publications • Burnside ER, De Winter F, Didangelos A, James ND, Andreica EC, Layard-Horsfall H, Muir EM, Verhaagen J, Bradbury EJ. Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury. Brain. 2018;141;8:2362–2381. • Didangelos A, Puglia M, Iberl M, Sanchez-Bellot C, Roschitzki B, Bradbury EJ. High-throughput proteomics reveal alarmins as amplifiers of tissue pathology and inflammation after spinal cord injury. Sci Rep. 2016;6:21607. • Ramer LM, Ramer MS, Bradbury EJ. Restoring function after spinal cord injury: towards clinical translation of experimental strategies. Lancet Neurol. 2014;13:1241-1256.

Centre for Stem Cells & Regenerative Medicine | 17 Professor Juan Burrone Professor of Development Neurophysiology PhD

Research interests My research interests are in understanding how neurons wire up to form a functional network in the brain. My lab focuses on three aspects of neuronal and circuit function: synaptic transmission and integration; synapse formation and maturation; and homeostatic plasticity of synapses.

Publications • Glebov OO, Jackson RE, Winterflood CM, Owen DM, Barker EA, Doherty P, Ewers H, Burrone J. Nanoscale structural plasticity of the active zone matrix modulates presynaptic function. Cell Rep. 2017;18(11):2715-2728. • Andreae LC & Burrone J. Spontaneous neurotransmitter release shapes dendritic arbors via long-range activation of NMDA receptors. Cell Rep. 2015;pii:S2211-1247. • Andreae L, Ben Fredj N, & Burrone J. Independent vesicle pools underlie different modes of release during neuronal development. J Neurosci. 2012;32:1867–74.

18 | Centre for Stem Cells & Regenerative Medicine Dr Ciro Chiappini Lecturer in Nanomaterials and Biointerfaces PhD (2011)

Research interests My research blends nanotechnology, bioengineering and cell biology to develop functional materials that direct cell behaviour. These materials interact dynamically with the intracellular milieu to detect, study and control biological processes at the molecular level. I leverage these controlled cell interactions to engineer platforms for regenerative medicine and precision medicine.

Publications • Chiappini C. Nanoneedle-based sensing in biological systems. ACS Sens. 2017;2(8):1086-1102. • Chiappini C, De Rosa E, Martinez JO, Liu X, Steele J, Stevens MM, Tasciotti E. Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization. Nat Mater. 2015;14:532-539. • Chiappini C, Campagnolo P, Almeida CS, Abbassi-Ghadi N, Chow LW, Hanna GB, Stevens MM. Mapping local cytosolic enzymatic activity in human esophageal mucosa with porous silicon nanoneedles. Adv mater. 2015;27, 5147 – 5152.

Centre for Stem Cells & Regenerative Medicine | 19 Dr Attila Csikász-Nagy Senior Lecturer in Computational and Systems Biology MSc (1998), PhD (2000)

Research interests We investigate molecular interaction networks, translate the proposed wiring diagram into mathematical forms and analyse the equations to understand the physiological responses the system might give. Key questions we investigate with this technique are related to the regulation of the cell cycle and pathways that influence cell division (such as cell growth, DNA damage and the circadian clock). We investigate cell-to-cell interactions from a “games on a cell-network” perspective. We consider the cell-to-cell interaction network as a graph and different cell types as players of a game. By applying rules from evolutionary game theory we follow how cells spread and tissue architecture changes in time.

Publications • Hernansaiz-Ballesteros RD, Cardelli L, Csikász-Nagy A. Single molecules can operate as primitive biological sensors, switches and oscillators. BMC Syst Biol. 2018;12(1):70. • Rizzetto S, Priami C, Csikász-Nagy A. Qualitative and quantitative protein complex prediction through proteome-wide simulations. PLoS Comput Biol. 2015;11(10):e1004424. • Honeth G, Schiavinotto T, Vaggi F, Marlow R, Kanno T, Shinomiya I, Lombardi S, Buchupalli B, Graham R, Gazinska P, Ramalingam V, Burchell J, Purushotham AD, Pinder SE, Csikász-Nagy A, Dontu G. Models of breast morphogenesis based on localization of stem cells in the developing mammary lobule. Stem Cell Rep. 2015;4:699-711.

20 | Centre for Stem Cells & Regenerative Medicine Dr Davide Danovi Director, Cell Phenotyping MD (Universita’ degli studi di Milano, 2000); PhD (European Institute of Oncology, Milan / Open University, 2004)

Research interests I am passionate about the biology of stem cells and their use as screening beds for high content imaging to model diseases and discover therapeutics. I have had the privilege to experience research in this domain in both academia and biotech. I believe the synergy between the academic and commercial world can effectively bring answers to important questions and solutions to unmet medical needs. Our group works within the framework of the Human Induced Pluripotent Stem Cells Initiative (HipSci) project (http://www.hipsci.org), funded by the Wellcome Trust and MRC. We study how intrinsic and extrinsic signals impact on human cells from healthy individuals and patients and provide a dedicated laboratory space for collaborative cell phenotyping.

Publications • Kilpinen H, Goncalves A, Leha A, Afzal V, Alasoo K, Ashford S, Bala S, Bensaddek D, Casale FP, Culley OJ, Danecek P, Faulconbridge A, Harrison PW, Kathuria A, McCarthy D, McCarthy SA, Meleckyte R, Memari Y, Moens N, Soares F, Mann A, Streeter I, Agu CA, Alderton A, Nelson R, Harper S, Patel M, White A, Patel SR, Clarke L, Halai R, Kirton CM, Kolb-Kokocinski A, Beales P, Birney E, Danovi D, Lamond AI, Ouwehand WH, Vallier L, Watt FM, Durbin R, Stegle O, Gaffney DJ. Common genetic variation drives molecular heterogeneity in human iPSCs. Nature. 2017;546(7658): 370-375. • Kerz M, Folarin A, Meleckyte R, Watt FM, Dobson RJ, Danovi D. A novel automated high-content analysis workflow capturing cell population dynamics from induced pluripotent stem cell live imaging data. J Biomol Screen. 2016;21(9):887-96. • Leha A, Moens N, Meleckyte R, Culley OJ, Gervasio MK, Kerz M, Reimer A, Cain SA, Streeter I, Folarin A, Stegle O, Kielty CM; HipSci Consortium., Durbin R, Watt FM, Danovi D. A high-content platform to characterise human induced pluripotent stem cell lines. Methods. 2016;1;96:85-96.

Centre for Stem Cells & Regenerative Medicine | 21 Professor Francesco Dazzi Professor of Regenerative and Haematological Medicine, KHP Lead for Cellular Therapies MD (Padua University Medical School); PhD (Padua University Medical School)

Research interests My main interest is the biology and clinical applications of cellular therapies in stem cell transplantation. I have pioneered a large immunotherapy programme for leukaemia patients and used animal models to investigate outstanding clinical problems. I have described and characterised the immunosuppressive effects of mesenchymal stromal cells (MSC), thereby identifying a new mechanism of immune tolerance with distinctive tissue repair activity. My current research programme is aimed at understanding the molecular basis of MSC anti-inflammatory properties and the interaction of MSC with myeloid cells. In parallel, after successfully testing MSC in pre-clinical models, we are now conducting UK wide clinical studies for their use in graft-versus- host disease and autoimmune disorders. The GMP-grade MSC preparations manufactured under my supervision at Imperial College and King’s College have been made available and more than 100 patients have been treated so far with exciting results.

Publications • Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Cheung TS, von Bonin M, Barbieri L, Halai K, Ward S, Weng L, Chakraverty R, Lombardi G, Watt FM, Orchard K, Marks DI, Apperley J, Bornhauser M, Walczak H, Bennett C, Dazzi F. Apoptosis in mesenchymal stromal cells induces in vivo recipientmediated immunomodulation. Sci Transl Med. 2017;9(416). • Raffaghello L, Dazzi F. Classification and biology of tumour associated stromal cells. Immunol Lett. 2015;168(2):175-82 • Fibbe WE, Dazzi F, LeBlanc K. MSCs: science and trials. Nat Med. 2013;19(7):812-3. • Lymperi S, Ersek A, Ferraro F, Dazzi F, Horwood NJ. Inhibition of osteoclast function reduces hematopoietic stem cell numbers in vivo. Blood. 2011;117(5):1540-9.

22 | Centre for Stem Cells & Regenerative Medicine Professor Anil Dhawan Director King’s Cell Therapy Unit, NIHR/Wellcome Clinical Research Facility, Cell Therapy Unit; Head, Hepatocyte Biology and Transplantation, Institute of Liver Studies, King’s College Hospital; Director Paediatric Liver GI and Nutrition Centre MBBS (1986), MD 1990

Research interests I established the first human hepatocyte transplantation programme in the UK. My laboratory has been active in translating human hepatocyte research such as the use of cryopreserved cells for clinical transplantation. Our latest success has been in-house development of hepatocytes embedded in alginate beads and their application to treat children with acute liver failure. Our current research is on the use of co-cultures of MSC and human hepatocytes for clinical transplantation. Mechanistic aspects of human hepatocyte biology as related to clinical transplantation and use of MSC and non-parenchymal cells has been our recent research interest. Several children with metabolic liver disease and acute liver failure have been the beneficiaries of our research in the last 10 years.

Publications • Iansante V, Chandrashekran A, Dhawan A. Cell-based liver therapies: past, present and future. Philos Trans R Soc Lond B Biol Sci. 2018;373(1750). • Filippi C, Dhawan A. Current status of human hepatocyte transplantation and its potential for Wilson Disease. Ann NY Acad Sci. 2014;1315(1):50-5. • Hughs RD, Mitry RR, Dhawan A. Current status of hepatocyte transplantation. Transplantation. 2012;93(4):342-7.

Centre for Stem Cells & Regenerative Medicine | 23 Professor Lucy (Luciana) Di Silvio Head of Tissue Engineering & Biophotonics, King’s College Dental Institute PhD (University College London)

Research interests Tissue engineering represents a major change in the treatment of diseased tissues and organs, which, until now, has generally involved organ transplantation or the use of conventional medical devices. The ageing population, sports injuries, trauma and cancer in younger people necessitates the development of more biological treatment modalities. My research focuses on a multidisciplinary approach for the repair and regeneration of biological tissues that can be guided through application of cells, materials (scaffolds) and biological signalling molecules. Our interests include establishing 2D/ 3D cell models to understand cell-material interactions and biocompatibility of novel materials for use as acellular or cellular scaffolds for tissue repair and regeneration. Applications include cell-seeded scaffolds to direct differentiation of stem cells for in vivo bone regeneration, vascularization of grafts ex-vivo and their integration with host tissue.

Publications • Tan Z, Parisi C, Di Silvio L, Dini D, Forte AE. Cryogenic 3D printing of super soft hydrogels. Sci Rep. 2017;7(1):16293. • Herath HM, Di Silvio L, Evans JR. Osteoblast response to zirconia with different topographies. Mater Sci Eng C Mater Biol Appl. 2015;57:363-70. • Buranawat B, Di Silvio L, Deb S, Nannmark U, Sennerby L, Palmer RM. Evaluation of a β-calcium metaphosphate bone Graft containing bone morphogenetic protein-7 in rabbit maxillary defects. J Periodontol. 2014;85(2):298-307.

24 | Centre for Stem Cells & Regenerative Medicine Dr Georgina Ellison-Hughes Reader in Physiology BSc (2000); PhD (2004)

Research interests My research focuses on understanding the role of tissue-specific stem cells in the homeostasis and regeneration of striated (skeletal and cardiac) muscle. Projects investigate cell homeostasis and response following injury; regeneration and repair therapies using resident stem-progenitor cells; the role of stem-progenitor cells in adaptive response to physiological exercise stimuli; the identification of mechanisms that govern stem-progenitor cell fate; and the effects of ageing and pathological status on stem-progenitor cell biology.

Publications • Vicinanza C, Aquila I, Scalise M, Cristiano F, Marino F, Cianflone E, Mancuso T, Marotta P, Sacco W, Lewis FC, Couch L, Shone V, Gritti G, Torella A, Smith AJ, Terracciano CMN, Britti D, Veltri P, Indolfi C, Nadal-Ginard B, Ellison-Hughes GM, Torella D. Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification. Cell Death Differ. 2017;24:2101-2116. • Smith AJ, Lewis FC, Aquila I, Waring CD, Nocera A, Agosti V, Nadal-Ginard B, Torella D, Ellison GM. Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart. Nat Protoc. 2014;9(7):1662- 81. • Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, Waring CD, Henning BJ, Stirparo GG, Papait R, Scarfò M, Agosti V, Viglietto G, Condorelli G, Indolfi C, Ottolenghi S, Torella D, Nadal-Ginard B. Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell. 2013;154(4):827-842.

Centre for Stem Cells & Regenerative Medicine | 25 Dr Gerald Finnerty FRCP Honorary Consultant Neurologist MA, MB, BS. PhD, FRCP

Research interests My interests include the role of experience-dependent plasticity in learning and disease; electrophysiology, confocal microscopy and functional magnetic resonance imaging to understand how the brain reorganises when challenged; application of this knowledge to develop treatments for acute neurological conditions such as stroke and chronic neurodegenerative diseases such as Alzheimer’s disease. Part of my research concerns disease modeling with human iPS cells.

Publications • Bennett SH, Kirby AJ, Finnerty GT. Rewiring the connectome: Evidence and effects. Neurosci Biobehav Rev. 2018;88:51- 62. • Barnes SJ, Cheetham CE, Liu Y, Bennett SH, Albieri G, Jorstad AA, Knott GW, Finnerty GT. Delayed and temporally imprecise neurotransmission in reorganizing cortical microcircuits. J Neurosci. 2015;35:9024-9037. • Cheetham CE, Barnes SJ, Albieri G, Knott G & Finnerty GT. Pansynaptic enlargement at adult cortical connections strengthened by experience. Cerebral Cortex. 2014;24:521 – 531.

26 | Centre for Stem Cells & Regenerative Medicine Dr Massimo Garriboli FEBPS FRCS(Eng) Consultant Paediatric Urologist, Evelina London Children’s Hospital; Honorary Senior Lecturer, King’s College London MD (Università Vita-Salute San Raffaele, Milan) Specialist in Paediatric Surgery (Università degli Studi di Milano); FRCS(Eng); FEBPS

Research interests My research interest is in amniotic fluid stem cells and decellularisation of organs for tissue engineering. In collaboration with Prof Paolo De Coppi (UCL) I have developed a decellularisation technique for obtaining acellular scaffolds from the bladder and other organs (intestine, oesophagus, lungs), in various species (rat, sheep, pig, human). In particular my main interest is focused on bladder replacement and I am exploring whether bladder reconstruction can be obtained by using the “composite cystoplasty”. I am attempting to develop a technique to augment the bladder using a vascularised de-epithelialised smooth muscle host tissue (eg colon) that is lined by autologous urothelium generated in cell culture.

Publications • Davidson JR, Wright NJ, Garriboli M. Urethral duplication with two hypospadic meati-an unusual variant. European J Pediatr Surg Rep. 2016;4(1):37-40. • Garriboli M, Radford A, Southgate J. Regenerative medicine in urology. Eur J Pediatr Surg. 2014;24(3):227-36. • Totonelli G, Maghsoudlou P, Georgiades F, Garriboli M, Koshy K, Turmaine M, Ashworth M, Sebire NJ, Pierro A, Eaton S, De Coppi P. Detergent enzymatic treatment for the development of a natural acellular matrix for oesophageal regeneration. Pediatr Surg Int. 2013;29(1):87-95.

Centre for Stem Cells & Regenerative Medicine | 27 Dr Eileen Gentleman Senior Research Fellow PhD (Tulane University 2005)

Research interests My research interests are in tissue engineering and regenerative medicine. My lab focuses on engineering the 3D cell niche to control stem cell differentiation for tissue engineering, particularly to regenerate bone and cartilage. We develop biomaterials that allow us to explore the roles mechanosensing and physical cues play in directing stem cell fate. We do this by designing, synthesising and testing highly defined hydrogel networks that allow us to explore fundamental questions in stem cell biology and enable us to create tissue engineering-based therapies. My other research interests include biomineralisation, materials-based characterisation of engineered tissues and the role of mechano- sensing in tissue development.

Publications • Ferreira SA, Faull PA, Seymour AJ, Yu TTL, Loaiza S, Auner HW, Snijders AP, Gentleman E. Neighboring cells override 3D hydrogel matrix cues to drive human MSC quiescence. Biomaterials. 2018;176:13-23. • Walters NJ, Gentleman E. Evolving insights in cell–matrix interactions: Elucidating how non-soluble properties of the extracellular niche direct stem cell fate. Acta Biomaterialia. 2015;11:3-16. • Autefage H, Gentleman E, Littmann E, Hedegaard MAB, von Erlach T, O’Donnell MD, Burden FR, Winkler DA, Stevens MM. Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials. Proc Natl Acad Sci USA. 2015;112(14):4280-85.

28 | Centre for Stem Cells & Regenerative Medicine Professor Agi Grigoriadis Professor of Bone & Cartilage Cell Biology BSc (University of Toronto, 1982); MSc (University of Toronto, 1984); PhD (University of Toronto, 1989)

Research interests My research interests are in the mechanism of bone and cartilage cell lineage commitment and activity during embryonic development as well as in adult bone/cartilage remodelling disorders and skeletal malignancies. We use mouse and human pluripotent stem cell approaches for the directed differentiation of stem cells to functional bone-forming osteoblasts, bone-resorbing osteoclasts and cartilage- forming chondrocytes; to better understand embryonic lineage specification and differentiation; and to provide suitable stem cell/precursor populations for regenerative and tissue engineering strategies. Transgenic and knockout mouse models are also being used to investigate Fos/AP-1 and FGFR signalling in bone tumour development and metastasis, and to study the role of osteoclasts in mammalian bone-remodelling disorders such as osteopetrosis.

Publications • Gharibi B, Ghuman MS, Cama G, Rawlinson SCF, Grigoriadis AE, Hughes FJ. Site-specific differences in osteoblast phenotype, mechanical loading response and estrogen receptor-related gene expression. Mol Cell Endocrinol. 2018;(18)30197-7. • Weekes D, Kashima TG, Zandueta C, Perurena N, Thomas DP, Sunters A, Vuillier C, Bozec A, E-Emir E, Miletich I, Patiño-Garcia A, Lecanda F and Grigoriadis AE. Regulation of osteosarcoma cell lung metastasis by the c-Fos/AP-1 target FGFR1. Oncogene. 2016;35:2852-2861. • Craft AM, Ahmed N, Rockel JS, Baht GS, Alman BA, Kandel RA, Grigoriadis AE and Keller GM. Specification of chondrocytes and cartilage tissues from embryonic stem cells. Development. 2013;140:2597-2610.

Centre for Stem Cells & Regenerative Medicine | 29 Dr Pierre Guermonprez Head of the Laboratory of Phagocyte Immunobiology PhD (Paris VI University, 2000)

Research interests My research addresses the role of monocytes and dendritic cells in adaptive immune responses. We are trying to understand i) how phagocytes develop from haematopoietic stem cells in homeostasis and during inflammation, ii) what cellular pathways underlie the ability of dendritic cells to activate T lymphocytes. In addition, we are developing new methods to induce the differentiation of iPSCs into dendritic cells for both basic and translational purposes such as cancer immunotherapy. iPSCs offer a convenient platform for gene editing via the CRISPR/Cas9 technology. iPSCs, dendritic cells deficient in immunoregulatory genes such as PD-L1 represent an attractive source of antigen presenting cells for adoptive immunotherapy.

Publications • Péan CB, Schiebler M, Tan SW, Sharrock JA, Kierdorf K, Brown KP, Maserumule MC, Menezes S, Pilátová M, Bronda K, Guermonprez P, Stramer BM, Andres Floto R, Dionne MS. Regulation of phagocyte triglyceride by a STAT-ATG2 pathway controls mycobacterial infection. Nat Commun. 2017;8:14642. Menezes S, Melandri D, Anselmi G, Perchet T, Loschko J, Dubrot J, Patel R, Gautier EL, Hugues S, Longhi MP, Henry JY, Quezada SA, Lauvau G, Lennon-Duménil AM, Gutiérrez- Martínez E, Bessis A, Gomez-Perdiguero E, Jacome-Galarza CE, Garner H, Geissmann F, Golub R, Nussenzweig MC, Guermonprez P. The heterogeneity of Ly6Chi monocytes controls their differentiation into iNOS, macrophages or monocyte-derived dendritic cells. Immunity. 2016;45(6): 1205-1218. • Guermonprez P, Helft J, Claser C, Deroubaix S, Karanje H, Gazumyan A, Darasse-Jèze G, Telerman SB, Breton G, Schreiber HA, Frias-Staheli N, Billerbeck E, Dorner M, Rice CM, Ploss A, Klein F, Swiecki M, Colonna M, Kamphorst AO, Meredith M, Niec R, Takacs C, Mikhail F, Hari A, Bosque D, Eisenreich T, Merad M, Shi Y, Ginhoux F, Rénia L, Urban BC, Nussenzweig MC. Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection. Nat Med. 2013(6):730-8.

30 | Centre for Stem Cells & Regenerative Medicine Dr Shukry J Habib Sir Henry Dale Research Fellow BSc (Technion, Israel, 2000); MSc (Tel Aviv University, 2002); PhD (LMU Munich, 2006)

Research interests Stem cells have the ability to make more stem cells (self-renew) and also to give rise to differentiated cells. We are interested in the external and internal cues that regulate mammalian stem cell division and cell fate choice. We aim to study and compare these cues during homeostasis, tissue regeneration and tumorigenesis. Our main focus lies on the role of Wnt signals in asymmetric cell division of embryonic and adult stem cells. To that end, we apply principles from organic chemistry, biochemistry, and stem cell biology in conjunction with advanced imaging techniques to further probe this biological phenomenon.

Publications • Lowndes M, Junyent S, Habib SJ. Constructing cellular niche properties by localized presentation of Wnt proteins on synthetic surfaces. Nat Protoc. 2017(7):1498-1512. • Lowndes M, Rotherham M, Price J, El Haj AJ, and Habib SJ. Immobilized WNT proteins act as a stem cell niche for tissue engineering. Stem Cell Rep. 2016;7(1):126-37. • Habib SJ, Chen BC, Tsai FC, Anastassiadis K, Meyer T, Betzig E, Nusse R. A localized Wnt signal orients asymmetric stem cell division in vitro. Science. 2013;339(6126):1445-8.

Centre for Stem Cells & Regenerative Medicine | 31 Professor Stephen Harridge Professor of Human and Applied Physiology, Director, Centre of Human & Aerospace Physiological Sciences to Centre for Human & Applied Physiological Sciences PhD (University of Birmingham, 1993)

Research interests My research takes a multidisciplinary approach to studying human skeletal muscle function and plasticity, with a particular focus on ageing. My laboratory uses primary cell culture techniques to study the behaviour of human muscle-derived stem cells, including both myogenic (satellite cells) and non-myogenic cells (fibroblasts). This is coupled to research on the physiology of the human ageing process using both whole body and single-fibre muscle mechanics approaches. In addition my laboratory is involved in a number of projects with clinical colleagues studying conditions where muscle mass is lost and function is impaired. These include patients in critical care acquired muscle weakness and patients with obesity hypoventilation syndrome.

Publications • Pollock RD, O’Brien KA, Daniels LJ, Nielsen KB, Rowlerson A, Duggal NA, Lazarus NR, Lord JM, Philp A, Harridge SDR. Properties of the vastus lateralis muscle in relation to age and p hysiological function in master cyclists aged 55-79 years. Aging Cell. 2018;17(2). • Agley CC, Lewis FC, Jaka O, Lazarus NR, Velloso C, Francis- West P, Ellison-Hughes GM & Harridge SDR. Active GSK3β and an intact β-catenin TCF complex are essential for the differentiation of human myogenic progenitor cells. Sci Rep. 2017;7(1):13189. • Agley CC, Rowlerson A, Velloso CP, Lazarus NR & Harridge SDR. Human skeletal muscle fibroblasts, but not myogenic cells, readily undergo adipogenic differentiation. J Cell Sci. 2013;126(24):5610-25.

32 | Centre for Stem Cells & Regenerative Medicine Dr Dusko Ilic Reader in Stem Cell Science MD (University of Belgrade, 1985); BSc (University of Belgrade, 1987); MSc (University of Belgrade, 1989); PhD (University of Tokyo, 1995)

Research interests My research interest lies in hESC, iPSC, MSC, reproductive and regenerative medicine. Key objectives of my work are to raise the standard of derivation and culture of human stem cells making them acceptable for cell-based therapies, to understand the molecular mechanisms of diseases using stem cells, and to realise the potential of normal and specific mutation-carrying pluripotent stem cells in drug discovery.

Publications • Floros VI, Pyle A, Dietmann S, Wei W, Tang WCW, Irie N, Payne B, Capalbo A, Noli L, Coxhead J, Hudson G, Crosier M, Strahl H, Khalaf Y, Saitou M, Ilic D, Surani MA, Chinnery PF. Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos. Nat Cell Biol. 2018(2):144-151. • Petrova A, Cell A, Jacquet L, Dafou D, Crumrine D, Hupe M, Arno M, Hobbs C, Cvoro A, Karagiannins P, Devito L, Sun R, Adame LC, Vaughan R, McGrath JA, Mauro TM, Ilic D. 3D in vitro model of a functional epidermal permeability barrier from hESC and iPSC. Stem Cell Rep. 2014;2(5):675-689. • Jacquet L, Stephenson E, Collins R, Patel H, Trussler J, Al- Bedaery R, Renwick P, Ogilvie C, Vaughan R, Ilic D. Strategy for the creation of clinical grade hESC line banks that HLA- match a target population. EMBO Mol Med. 2013;5(1):10-7.

Centre for Stem Cells & Regenerative Medicine | 33 Dr Thomas Iskratsch Research Fellow PhD

Research interests The cellular microenvironment, which is defined by both chemical and physical/mechanical parameters, guides cell migration, growth or differentiation during development to shape the heart and other organs. My research addresses fundamental mechanisms of how mechanical forces regulate cell behavior and in particular the formation and maintenance of the contractile myofibrils in heart cells during heart development and in cardiac disease. To answer these questions I use stem cell derived cardiomyocytes together with picoNewton (pN) strength force probing (micropillar arrays), micro printing, live cell (superresolution) fluorescent imaging, and specifically designed protein activity sensors (fluorescence quenching FRET).

Publications • Iskratsch T, Yu CH, Mathur A, Liu SM, Stévenin V, Dwyer J, Hone J, Ehler E, Sheetz M. FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration. Dev Cell. 2013;27(5):545-59. • Iskratsch T, Reijntjes S, Dwyer J, Toselli P, Dégano IR, Dominguez I, Ehler E. Two distinct phosphorylation events govern the function of muscle FHOD3. Cell Mol Life Sci. 2013;70(5):893-908. • Iskratsch T, Lange S, Dwyer J., Kho AL, dos Remedios C, Ehler E. Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance. J Cell Biol. 2010;191(6):1159-72.

34 | Centre for Stem Cells & Regenerative Medicine Professor Peter Jones Professor of Endocrine Biology BSc (1979); PhD (1983)

Research interests My research interests have been focused on the regulation of hormone secretion. I obtained my PhD studying peptide hormones in the central nervous system at the National Institute for Medical Research, London. I started working on beta-cell function in diabetes as a postdoctoral fellow at Queen Elizabeth College in 1984 and my main research interest remains the pancreatic beta- cell. Current work is focused on improving islet transplantation as a therapy for Type 1 diabetes by the generation of functional beta- cell substitutes, and by using mesenchymal stem cells to enhance graft survival and function. I am also interested in the regulation of beta-cell mass during pregnancy and in G-protein coupled receptors as therapeutic targets for Type 2 diabetes. Experimental approaches range from in vitro molecular/cell biology of the beta-cell to animal models of diabetes and islet transplantation.

Publications • Arzouni AA, Vargas-Seymour A, Rackham C, Dhadda P, Huang G-C, Choudhary P, King A and Jones PM. Mesenchymal stromal cells improve human islet function through secreted products and extracellular matrix. Clin Sci (Lond). 2017;131(23):2835-2845. • Rackham CL, Vargas A, Hawkes RG, Amisten S, Persaud SJ, Austin AL, King AJF, Jones PM. Annexin A1 is a key modulator of MSC-mediated improvements in islet function. Diabetes. 2016;65:129-139. • Clarkin CE, King AJ, Dhadda P, Chagastelles P, Nardi N, Wheeler-Jones CP, Jones PM. ALK5 inhibition reverses impairment of islet endothelial cell viability by endogenous mesenchymal stromal cells. Stem Cells. 2013;31:547-559.

Centre for Stem Cells & Regenerative Medicine | 35 Dr Aileen King Senior Lecturer in Pharmacology BSc (1995); PhD (2001)

Research interests My research focuses on mouse models of diabetes. My particular interest is the improvement of islet transplantation outcome. Approaches that I use include encapsulation strategies, adjunctive stem cell therapies (co-transplantation with mesenchymal stem cells) and pharmacological strategies that may improve beta- cell and/or endothelial cell survival. We have transplanted islets into a variety of sites in diabetic mice including subcutaneously, intraperitoneally, under the kidney capsule and into the liver through the portal vein. Graft outcome is monitored by blood glucose measurements, serum insulin and immunohistochemistry analysis of the graft. Recent experiments using mesenchymal stem cells as an adjunctive therapy in islet transplantation have shown improvements in blood glucose homeostasis as well as increased revascularization of the grafts. Our current research is focused on understanding some of the underlying mechanisms.

Publications • Rackham CL, Dhadda PK, Simpson SJS, Godazgar M, King AJF, Jones PM. Composite mesenchymal stromal cell Islets: Implications for transplantation via the clinically preferred intraportal route. Transplant Direct. 2018;4(4):e354. • King AJ, Griffiths LA, Persaud SJ, Jones PM, Howell SL, Welsh N. Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome. Ups J Med Sci. 2016;121(2):140-5. • Kerby A, Jones ES, Jones PM, King AJ. Co-transplantation of islets with mesenchymal stem cells in microcapsules demonstrates graft outcome can be improved in an isolated-graft model of islet transplantation in mice. Cytotherapy. 2013;15(2):192-200.

36 | Centre for Stem Cells & Regenerative Medicine Dr Robert Knight Lecturer – Developmental Genetics PhD

Research interests My group is interested in the molecules and cellular events that are important for the development of the vertebrate head. In particular, we wish to understand how the muscles, connective tissues and motor nerves are coordinated to form such a complicated but essential structure. We use the zebrafish as a model for understanding how the vertebrate head develops as embryos are transparent, allowing us to observe them in vivo. By combining this with fluorescence microscopy, we are able to observe cell behaviour under different experimental conditions. We are currently focusing on two signalling pathways that are potentially important for both muscle and motor neuron development. Our current data suggests that a set of functionally related muscles requires one of these pathways for their development. It also appears to be important for the development of motor nerves that contact these muscles, suggesting a mechanism for coordinating the development of two different cell types that form a functional neuromuscular unit. Some aspects of head development such as motor nerve innervation are well conserved between different vertebrates, but others, such as muscle shape and position in the head, are not. Ultimately, we aim to show whether our results from zebrafish are relevant to the development of head muscles and motor neurons in other animals.

Publications • Mitchell CA, Poland SP, Seyforth J, Nedbal J, Gelot T, Huq T, Holst G, Knight RD, Ameer-Beg S. Functional in vivo imaging using fluorescence lifetime light-sheet microscopy. Opt Lett. 2017;42,7;1269-1272. • Moyle LA, Blanc E, Jaka O, Prueller J, Banerji CR, Tedesco FS, Harridge SD, Knight RD, Zammit PS. Ret function in muscle stem cell function points to tyrosine kinase inhibitor therapy for fascioscapulohumeral muscle dystrophy. eLife. 2016;5. pii: e11405 • Knappe S, Zammit P, Knight RD. A population of Pax7- expressing muscle progenitor cells show differential responses to muscle injury dependent on developmental stage and injury extent. Front Aging Neurosci. 2015;7:161.

Centre for Stem Cells & Regenerative Medicine | 37 Dr Ivo Lieberam Senior Lecturer Dr. rer. nat (University of Cologne, 2000)

Research interests The aim of my current research program is to explore how pluripotent stem cell technology can be harnessed to understand the formation, function and dysfunction of neural circuits that control motor behaviour, and how stem cell-derived tissue can be used to restore motor function in humans. To this end, my group is developing: 1. Bio-chips that carry neuromuscular circuits assembled from stem cell-derived, defined cell populations, such as motor neurons, astrocytes and muscle. The aim of this project is to study normal neural development and degenerative disease processes in vitro. 2. A new type of implantable neural prosthesis capable of pacing skeletal muscle. The device is composed of optogenetic stem cell- derived neural tissue, as well as an opto-electronic pacemaker. In the long-run, we intend to use this device to restore vital motor functions, such as breathing, in patients that have lost motor neurons as a result of spinal cord injury or motor neuron disease.

Publications • Bryson JB, Machado CB, Lieberam I, Greensmith L. Restoring motor function using optogenetics and neural engraftment. Curr Opin Biotechnol. 2016;40:75-81. • Bryson JB, Machado CB, Crossley M, Stevenson D, Bros-Facer V, Burrone J, Greensmith L, Lieberam I. Optical control of muscle function by transplantation of stem cell-derived motor neurons in mice. Science. 2014;344(6179):94-7. • Machado CB, Kanning KC, Kreis P, Stevenson D, Crossley M, Nowak M, Iacovino M, Kyba M, Chambers D, Blanc E, Lieberam I. Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons. Development. 2014;141(4):784-94.

38 | Centre for Stem Cells & Regenerative Medicine Dr Karen Liu Reader in Signalling & Development King’s Innovation Fellow AB (Columbia University, 1994); PhD (University of California Berkeley, 2003)

Research interests Our lab focuses on the development of the neural crest. Undifferentiated neural crest cells undergo epithelial-mesenchymal transformations (EMT), migrate from the neural tube, and populate distant destinations. These cells display incredible plasticity, giving rise to diverse tissues ranging from bone and cartilage to adipocytes and neurons. Our research makes use of multiple animal models, including frog, mouse, chick and humans. We also bring together biology and chemistry, designing new tools to study development and differentiation over time. Current projects include work on mammalian neural crest stem cells, migratory neural crest, contributions of the neural crest to head structures, and human craniofacial anomalies.

Publications • Gonzalez Malagon SG, Lopez Muñoz AM, Doro D, Bolger TG, Poon E, Tucker ER, Adel Al-Lami H, Krause M, Phiel CJ, Chesler L, Liu KJ. Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus. Nat Commun. 2018;9(1):1126. • Tabler JM, Barrell WB, Szabo-Rogers HL, Healy C, Yeung Y, Perdiguero EG, Schulz C, Yannakoudakis BZ, Mesbahi A, Wlodarczyk B, Geissmann F, Finnell RH, Wallingford JB, Liu KJ. Fuz mutant mice reveal shared mechanisms between ciliopathies and FGF-related syndromes. Dev Cell. 2013;25: 623-635. • Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science. 2012;336:86-90.

Centre for Stem Cells & Regenerative Medicine | 39 Dr Alexis Lomakin King’s Prize Fellow PhD (Lomonosov Moscow State University, Russia and the University of Connecticut, USA, 2010)

Research interests Cells that make up tissues and organs in our bodies experience various spatial and mechanical constraints depending on their anatomical location. To cope with such constraints, the cells alter their shape and size in an adaptive response essential for normal cell division, movements, and survival. Our lab is interested in how cells decode external spatio-mechanical signals into internal biochemical cues controlling morphogenetic cell behaviors in different environmental contexts. To answer this question, we employ an interdisciplinary approach combining bioengineering technologies with molecular genetics, experimental cell biophysics, quantitative videomicroscopy, and computational modeling. This knowledge is a fundamental prerequisite for understanding the etiology and pathogenesis of acquired and congenital diseases that involve defects in mechanical cell regulation, including laminopathies and tumor progression to metastasis.

Publications • Lomakin AJ, Nader G, Piel M. Forcing entry into the nucleus. Dev Cell. 2017(43):547-548. • Lomakin AJ, Lee KC, Han SJ, Bui DA, Davidson M, Mogilner A, Danuser G. Competition for actin between two distinct F-actin networks defines a bistable switch for cell polarization. Nat Cell Biol. 2015(11):1435-1445. • Lomakin AJ, Semenova I, Zaliapin I, Kraikivski P, Nadezhdina E, Slepchenko BM, Akhmanova A, Rodionov V. CLIP-170-dependent capture of membrane organelles by microtubules initiates minus-end directed transport. Dev Cell. 2009;17(3):323-33.

40 | Centre for Stem Cells & Regenerative Medicine Professor Giovanna Lombardi Professor of Human Transplant Immunology BSc (University of Rome, 1978); PhD (University of Rome, 1981)

Research interests My scientific interest is in the mechanisms of graft rejection and the role of regulatory T cells (Tregs) in the maintenance of tolerance. The projects in my laboratory focus on different aspects of Treg biology, from their heterogeneity to the role of innate receptors in their function. In recent years, my laboratory has developed protocols for the use of Tregs in the clinic. Tregs have been manipulated in vitro to confer specificity for donor antigens, demonstrating the advantage of this approach. In collaboration with other scientists and clinicians within KHP and other groups within the UK and abroad I have completed two clinical trials in which expanded polyclonal Tregs have been injected into patients that have received either renal or liver transplants with the aim of inducing transplantation tolerance. New clinical trials in transplant patients using donor-specific Tregs are in preparation. Based on my experience in solid organ transplantation, my interest in stem cells is to evaluate whether once transplanted they are immunogenic, with a view to applying Treg therapy to prolong their survival.

Publications • Boardman DA, Philippeos C, Fruhwirth GO, Ibrahim MA, Hannen RF, Cooper D, Marelli-Berg FM, Watt FM, Lechler RI, Maher J, Smyth LA, Lombardi G. Expression of a chimeric antigen receptor specific for donor HLA class I enhances the potency of human regulatory T cells in preventing human skin transplant rejection. Am J Transplant. 2017;17(4):931-943. • Halim L. Romano M, McGregory R, Correa I, Pavlidis P, Grageda N, Hoong SJ, Yuksel M, Jassem W, Hannen RF, Ong M, Mckinney O, Havee B, Karagiannis SN, Powell N, Lechler RI, Nova-Lamperti E*, Lombardi G*. *equal contribution. An atlas of human regulatory T helper-like cells reveals features of TH2-like Tregs that support a tumorigenic environment. Cell Rep. 2017;20: 757-770. • Sagoo P, Ali N, Garg G, Nestle FO, Lechler RI, Lombardi G. Human Tregs with alloantigenspecificity are more potent inhibitors of alloimmune damage to human skin grafts than polyclonal Tregs. Sci Transl Med. 2011;(3):83.

Centre for Stem Cells & Regenerative Medicine | 41 Dr Magnus Lynch Consultant Dermatologist and Senior Lecturer MA MB BChir (University of Cambridge, 2003); DPhil (University of Oxford, 2011); MRCS(Royal College of Surgeons, 2005); MRCP (Royal College of Physicians, 2006); MRCP(Derm) (Royal College of Physicians, 2017)

Research Interests My interests lie in the application of single cell technologies to understand the mechanisms by which cellular identity is established and maintained in a three-dimensional mammalian tissue – the human skin. Previous work has combined ultra deep sequencing with computational modeling to study the earliest stages in the clonal evolution of non-melanoma skin cancer and single-cell and spatial transcriptional profiling to dissect lineage relationships of fibroblasts within the human dermis. An objective of future work is to combine single cell genetic and epigenetic profiling with advanced imaging methodologies to build integrative computational models describing the spatial and temporal dynamics of cells within the human skin in both health and disease.

Publications • Philippeos C, Telerman S, Oulès B, Pisco A, Shaw T, Elgueta R, Lombardi G, Driskell R, Soldin M, Lynch MD* and Watt F*. *equal contribution. Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations. J Invest Dermatol. 2018;38(4):811-825. • Lynch MD, Watt FM. Fibroblast heterogeneity: Implications for human disease. J Clin Invest. 2018;128(1):26-35. • Lynch MD, Lynch CNS, Craythorne E, Liakath-Ali K, Mallipeddi R, Barker JN and Watt FM. Spatial constraints govern competition of mutant clones in human epidermis. Nature Commun. 2017(1):1119.

42 | Centre for Stem Cells & Regenerative Medicine Dr John Maher FRCPath Hon. Consultant and Senior Lecturer in Immunology, KCL and King’s College London NHS Foundation Trust; Consultant in Immunology, Barnet Hospital and Royal Free NHS Foundation Trust BA Mod (Biochem, 1984); MB BCh BAO (1987); MRCPI (1989); MRCP(UK) (1990); PhD (1995); MSc (1998); MRCPath (Immunol; by examination) (2003); FRCPath (2008)

Research interests My group is interested in developing adoptive T-cell immunotherapy approaches for cancer (and potentially other diseases) using chimeric antigen receptor (CAR)-engineered and gamma delta T-cells. The primary focus of our work is to develop innovative approaches to improve efficacy, safety and quality of cell products that may be applied to the treatment of solid and haematological malignancy in humans. Our first phase I trial of CAR T-cell immunotherapy has recently been initiated (clinicaltrials.gov; NCT01818323).

Publications • Thayaparan T, Petrovic RM, Achkova DY, Zabinski T, Davies DM, Klampatsa A, Parente-Pereira AC, Whilding LM, van der Stegen SJ, Woodman N, Sheaff M, Cochran JR, Spicer JF, Maher J. CAR T-cell immunotherapy of MET- expressing malignant mesothelioma. Oncoimmunology. 2017;6(12):e1363137. • Parente-Pereira AC, Shmeeda H, Whilding L, Zambirinis C, Foster J, van der Stegen SJC, Mather S, Beatson R, Zabinski T, Brewig N, Sosabowski J, Ghaem-Maghami S, Gabizon A, Wilkie S, Maher J. Adoptive immunotherapy of epithelial ovarian cancer with Vγ9Vδ2 T-cells, potentiated by liposomal alendronic acid. J Immunol. 2014;193(11):5557-66. • Davies DM, Foster J, van der Stegen S, Parente ACP, Chiapero- Stanke L, Delinassios G, Burbridge SE, Kao V, Liu Z, Bosshard- Carter L, van Schalkwyk MCI, Box C, Eccles SA, Mather SJ, Wilkie S, Maher J. Flexible targeting of ErbB dimers that drive tumorigenesis using genetically engineered T-cells. Mol Med. 2012;18(1):565-76.

Centre for Stem Cells & Regenerative Medicine | 43 Professor Michael Malim Professor of Infectious Diseases Head of Division of Immunology, Infection & Inflammatory Disease; Director, MRC DTP in Biomedical Sciences DPhil

Research interests The outcome of viral infection is determined by competition between the virus and its host, and in particular the balance between host-encoded dependency factors whose exploitation promotes virus growth, and immune and inflammatory responses that control or eliminate infection. Our group focuses on the retrovirus HIV-1, the etiologic agent of AIDS, where we employ an array of molecular-genetic, cultured cell, biochemical, structural, bioinformatic and cohort-based methods to address the biological principles that underpin virus replication and disease. Our collaboration with CSCRM research is based on the concept of using natural variation in human iPSC phenotype as the basis for identifying novel regulators of HIV-1 infection. Accordingly, we are exploiting in vitro variability in the susceptibility of iPSC lines to HIV-1 infection to seek correlations with genetic, transcriptomic and proteomic signatures. The goal is to drive targeted experiments defining molecular causation, identify new regulatory pathways governing HIV-1 infection, and help inform future genome modification strategies.

Publications • Pollpeter D, Parsons M, Sobala AE, Coxhead S, Lang RD, Bruns AM, Papaioannou S, McDonnell JM, Apolonia L, Chowdhury JA, Horvath CM, Malim MH. Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G. Nat Microbiol. 2018;3(2):220-233. • Apolonia L, Schulz R, Curk T, Rocha P, Swanson CM, Schaller T, Ule J, Malim MH. Promiscuous RNA binding ensures effective encapsidation of APOBEC3 proteins by HIV-1. PLoS Pathog. 2015;11(1):e1004609. • Goujon C, Moncorgé O, Bauby H, Doyle T, Ward CC, Schaller T, Hué S, Barclay WS, Schulz R, Malim MH. Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature. 2013;502(7472):559-62.

44 | Centre for Stem Cells & Regenerative Medicine Professor Manuel Mayr British Heart Foundation Professor in Cardiovascular Proteomics MD (1998, Institute of Pathophysiology, Innsbruck, Austria); Medical degree with distinction “sub auspiciis presidentis rei publicae“; PhD (University of London, United Kingdom 2005); Visiting Professor (University of Heidelberg, Germany 2014)

Research interests My group uses proteomics in combination with other postgenomics technologies, such as lipidomics and microRNA profiling, to integrate molecular information in biological networks. While studying molecular interactions has been a research focus for many years and has provided important insights, the attention has now shifted towards a more integrative biology approach. Using proteomics, we have made a major contribution to the longstanding debate about whether endothelial progenitors are true stem cells. Other examples of recent research include our systematic study on circulating microRNAs to identify characteristic signatures of small non-coding RNAs for diabetes and extracellular matrix proteomics to identify inflammatory mediators that can predict cardiovascular events before they manifest.

Publications • Langley SR, Willeit K, Didangelos A, Matic LP, Skroblin P, Barallobre-Barreiro J, Lengquist M, Rungger G, Kapustin A, Kedenko L, Molenaar C, Lu R, Barwari T, Suna G, Yin X, Iglseder B, Paulweber B, Willeit P, Shalhoub J, Pasterkamp G, Davies AH, Monaco C, Hedin U, Shanahan CM, Willeit J, Kiechl S, Mayr M. Extracellular matrix proteomics identifies molecular signature of symptomatic carotid plaques. J Clin Invest. 2014;15(2):13953. • Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res Circ Res. 2010;107(6):810-7. • Prokopi M, Pula G, Mayr U, Devue C, Gallagher J, Xiao Q, Boulanger CM, Westwood N, Urbich C, Willeit J, Steiner M, Breuss J, Xu Q, Kiechl S, Mayr M. Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures. Blood. 2009;114:723-732.

Centre for Stem Cells & Regenerative Medicine | 45 Professor John McGrath Mary Dunhill Chair in Cutaneous Medicine MBBS MD FRCP FMedSci, MD (Guy’s Hospital, 1985)

Research interests My research interest lies in discovering what causes inherited skin diseases, how these abnormalities disrupt skin structure and function, and what we – as clinician-scientists – can do to develop new clinical and therapeutic benefits for people with genetic skin diseases. Key objectives are to improve and expand prenatal testing options for families at risk for inherited skin diseases and to advance new therapies for affected individuals, which include cell-based, gene, protein and drug treatments.

Publications • Lee JYW, Hsu CK, Michael M, Nanda A, Liu L, McMillan JR, Pourreyron C, Takeichi T, Tolar J, Reid E, Hayday T, Blumen SC, Abu-Mouch S, Straussberg R, Basel-Vanagaite L, Barhum Y, Zouabi Y, Al-Ajmi , Huang HY, Lin TC, Akiyama M, Lee JYY, McLean WHI, Simpson MA, Parsons M, McGrath JA. Large intragenic deletion in DSTYK underlies autosomal recessive complicated spastic paraparesis, SPG23. Am J Hum Genet. 2017;100:364-370. • Zhong FL, Mamaï O, Sborgi L, Boussofara L, Hopkins R, Robinson K, Szeverényi I, Takeichi T, Balaji R, Lau A, Tye H, Roy K, Bonnard C, Ahl PJ, Jones LA, Baker PJ, Lacina L, Otsuka A, Fournie PR, Malecaze F, Lane EB, Akiyama M, Kabashima K, Connolly JE, Masters SL, Soler VJ, Omar SS, McGrath JA, Nedelcu R, Gribaa M, Denguezli M, Saad A, Hiller S, Reversade B. Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation. Cell. 2016;167:187-202. • Petrof G, Lwin SM, Martinez-Queipo M, Abdul-Wahab A, Tso S, Mellerio JE, Slaper-Cortenbach I, Boelens JJ, Tolar J, VeysP, Ofuya M, Peacock JL, Martinez AE, McGrath JA. Potential of systemic allogeneic mesenchymal stromal cell therapy for children with recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2015;135(9):2319-2321.

46 | Centre for Stem Cells & Regenerative Medicine Dr Isabelle Miletich Lecturer – Craniofacial Development & Stem Cell Biology DDS (Bordeaux II University, France, 1994); BSc (Bordeaux II University, France, 1994); MSc (Paris XI, France, 1996); PhD (Paris XI, France 2000)

Research interests My main research interest is the biology of salivary gland stem cells, with a focus on the characterization of salivary gland stem/ progenitor cells and the signalling pathways activating these cells following salivary gland injury. Most of our studies are carried out in transgenic mice in which genetically labeled cell populations can be monitored during salivary gland injury and repair. My laboratory is also interested in the signalling pathways controlling the early steps of salivary gland embryonic development.

Publications • Star H, Chandrasekaran D, Miletich I, Tucker AS. Impact of hypofunctional occlusion on upper and lower molars after cessation of root development in adult mice. Eur J Orthod. 2017;39(3):243-250. • Lapthanasupkul P, Feng J, Mantesso A, Takada-Horisawa Y, Vidal M, Koseki H, Wang L, An Z, Miletich I, Sharpe PT. Ring1a/b polycomb proteins regulate the mesenchymal stem cell niche in continuously growing incisors. Dev Biol. 2012;367:140-153. • Miletich I, Yu WY, Zhang R, Yang K, Caixeta de Andrade S, Pereira SF, Ohazama A, Mock OB, Buchner G, Sealby J, Webster Z, Zhao M, Bei M, Sharpe PT. Developmental stalling and organ-autonomous regulation of morphogenesis. Proc Natl Acad Sci USA. 2011;108(48):19270-5.

Centre for Stem Cells & Regenerative Medicine | 47 Mr Bijan Modarai FRCS Reader in Vascular Surgery, British Heart Foundation Intermediate Fellow, Consultant Vascular Surgeon MB BS (University of London, 1998); MRCS (Royal College of Surgeons of England, 2002); PhD (University of London, 2006); FRCS (Royal College of Surgeons of England, 2010)

Research interests My research involves developing novel therapeutic, diagnostic and preventative strategies for patients with critical limb ischaemia. This research programme, in partnership with national and international collaborators, focuses on angiogenesis in tissue remodelling, angiogenic cell therapies, the use of biomaterials to enhance cell therapy and novel imaging techniques applied to vascular disease. We are studying the angiogenic properties of monocytes and adipose derived stem cells isolated from patients with critical limb ischaemia. We also have an active collaboration to investigate the use of microencapsulation for improving the efficacy of angiogenic cell therapies. These studies are running in parallel with a first in man study aimed at demonstrating the feasibility of using angiogenic monocytes to revascularise the limb in ‘no option’ patients with critical limb ischaemia who would otherwise require an amputation.

Publications • Bajwa A, Wesolowski R, Saha P, Ludwinski F, Patel A, Smith A, Nagel E, Modarai B. Blood oxygenation level dependent (BOLD)-CMR derived measures in critical limb ischemia and changes with revascularization. J Am Coll Cardiol. 2016;67(4):420-431. • Patel AS, Smith A, Nucera S, Biziato D, Saha P, Attia RQ, Humphries J, Mattock K, Grover SP, Lyons OT, Guidotti LG, Siow R, Ivetic A, Egginton S, Waltham M, Naldini L, De Palma M, Modarai B. TIE2-expressing monocytes/ macrophages regulate revascularization of the ischemic limb. EMBO Mol Med. 2013;5:858. • Patel A, Smith A, Attia R, Saha P, Jayasinghe S*, Modarai B*. *joint senior authors. Encapsulation of angiogenic monocytes using bio-spraying technology. Integ Biol. 2012;4(6):628-32.

48 | Centre for Stem Cells & Regenerative Medicine Professor Ghulam Mufti FRCP Professor of Haematological Oncology Consultant Haematologist, King’s College Hospital MD (University of Kashmir, 1973)

Research interests I am head of the Section of Haemato-oncology at King’s, a centre for basic and translational laboratory research into haematological malignancies. We also carry out specialist tests through the Haematological Malignancies Diagnostic Centre, which provides a diagnostic service to our local NHS partners and the South East of England. Our research includes identifying and exploiting genetic changes and molecular characteristics of proliferation to further develop and test novel interventions and immunotherapies. My specific interests are in molecular evolution and treatment of myelodysplastic syndromes; immune gene therapy for leukaemia and bone marrow transplantation for myeloid malignancies.

Publications • Chitre S, Stölzel F, Cuthill K, Streetly M, Graham C, Dill C, Mohamedali A, Smith A, Schetelig J, Altmann H, Bornhäuser M, Mufti GJ. Clonal hematopoiesis in patients with multiple myeloma undergoing autologous stem cell transplantation. Leukemia. 2018;32(9):2020-2024. • Gaymes TJ, Mohamedali AM, Patterson M, Matto N, Smith A, Kulasekararaj A, Chelliah R, Curtin N, Farzaneh F, Shall S, Mufti GJ. Microsatellite instability induced mutations in DNA repair genes CtIP and MRE11 confer hypersensitivity to poly (ADP-ribose) polymerase inhibitors in myeloid malignancies. Haematologica. 2013;98:1397-1406. • Costantini B, Kordasti SY, Kulasekararaj AG, Jiang J, Seidl T, Perez Abellan P, Mohamedali A, Thomas NSB, Farzaneh F, Mufti GJ. The effects of 5-azacytidine on the function and number of regulatory T-cells and T-effectors in myelodysplastic syndrome. Haematologica. 2013;98:1196-1205.

Centre for Stem Cells & Regenerative Medicine | 49 Dr Joana F Neves RCUK/UKRI Rutherford Fund Fellow and Group Leader BSc (Porto University, Portugal 2006); PhD (Coimbra University, Portugal and QMUL, UK 2011)

Research Interests I am an immunologist studying intestinal unconventional lymphocyte populations. I have established a novel in vitro system of lymphocyte culture in intestinal organoids that mimics the intestinal environment. Using this system I am now dissecting mechanisms that govern the interactions between lymphocytes, intestinal epithelial cells and the gut microbiota. Such interactions are critical for the maintenance of intestinal homeostasis. Their disruption has local and systemic consequences and has been associated with several diseases such as Inflammatory Bowel Disease (IBD), diabetes, obesity and cancer.

Publications • Iyer SS, Gensollen T, Gandhi A, Oh SF, Neves JF, Collin F, Lavin R, Serra C, Glickman J, Silva PSA, R. Sartor RB, Besra G, Hauser R, Maxwell A, Llebaria A, Blumberg RS. Dietary and microbial oxazoles induce intestinal inflammation by modulating epithelial derived aryl hydrocarbon receptor responses. Cell. 2018;173(5):1123-1134. • Olszak T*, Neves JF*, Dowds CM*, Baker K, Glickman J, Davidson NO, Lin CS, Jobin C, Brand S, Sotlar K, Wada K, Katayama K, Nakajima A, Mizuguchi H, Kawasaki K, Nagata K, Müller W, Snapper SB, Schreiber S, Kaser A, Zeissig S*, Blumberg RS*. Protective mucosal immunity mediated by epithelial CD1d and IL-10. Nature. 2014;509(7501):497-502. *These authors contributed equally to this work. • Mahtani-Patching J*, Neves JF*, Pang DJ, Stoenchev KV, Aguirre-Blanco AM, Silva-Santos B, Pennington DJ. PreTCR and TCRγδ signal initiation in thymocyte progenitors does not require domains implicated in receptor oligomerization. Sci Signal. 2011;4(182):ra47. *These authors contributed equally to this work.

50 | Centre for Stem Cells & Regenerative Medicine Professor Antonio Pagliuca Consultant Haematologist (1994) and Clinical Professor of Stem Cell Transplantation (2011) King’s College Hospital FT and King’s College London Medical Director Networked Services 2016-present MBBS (1983), MA, FRCP, FRCPath

Research Interests My research interests are in the development and delivery of novel stem cell transplant programs at King’s. Over the past 30 years we have created the largest adult program in the UK, with an international footprint across all diseases. We were the first to introduce reduced toxicity transplants in the late 1990’s and then went on to develop the national cord and haplo-identical programs in the UK. We have also introduced the largest autoimmune program, specifically in multiple sclerosis. Over the past 2 years we have started an allogeneic CAR-T program in adult ALL and we are developing the CAR program in myeloma, lymphoma and myeloid malignancies. My research group is also working in the field of infection in the immunocompromised host.

Publications • Ceesay MM, Kordasti S, Rufaie E, Lea N, Smith M, Wade J, Douiri A, Mufti GJ, Pagliuca A. Baseline cytokine profiling identifies novel risk factors for invasive fungal disease among haematology patients undergoing intensive chemotherapy or haematopoietic stem cell transplantation. J Infect. 2016;73(3):280-8. • Raj K, Pagliuca A, Bradstock K, Noriega V, Potter V, Streetly M, McLornan D, Kazmi M, Marsh J, Kwan J, Huang G, Getzendaner L, Lee S, Guthrie KA, Mufti GJ, O’Donnell P. Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning. Biol Blood Marrow Transplant. 2014;20(6):890-5. • Ho AY, Pagliuca A, Kenyon M, Parker JE, Mijovic A, Devereux S, Mufti GJ. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning. Blood. 2004;104(6):1616-23.

Centre for Stem Cells & Regenerative Medicine | 51 Professor Carmine Pariante Professor in Biological Psychiatry and Head of Section, Institute of Psychiatry MD (1990); MRCPsych (1999); Specialist in Psychiatry, Honours Degree (1994); Section 12 approval (1999); PhD (2003); Certificate of Completion of Specialist Training in General Adult Psychiatry, Endorsement in Liaison Psychiatry, London Deanery (2004)

Research interests Together with my co-workers in the Section of Perinatal Psychiatry & Stress, Psychiatry and Immunology, I am studying the role of stress hormones in the pathogenesis of mental disorders and in the mechanism of action of psychotropic drugs. I use a variety of experimental models and clinical samples, including subjects with depression, first-episode psychosis, and psychiatric problems during pregnancy.

Publications • Cattaneo A, Cattane N, Malpighi C, Czamara D, Suarez A, Mariani N, Kajantie E, Luoni A, Eriksson JG, Lahti J, Mondelli V, Dazzan P, Räikkönen K, Binder EB, Riva MA, Pariante CM. FoxO1, A2M, and TGF-β1: three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses. Mol Psychiatry. 2018;23(11):2192-2208. • Egeland M, Zunszain PA, Pariante CM. Molecular mechanisms in the regulation of adult neurogenesis during stress. Nat Rev Neurosci. 2015;16:189-200. • Zunszain PA, Anacker C, Cattaneo A, Choudhury S, Musaelyan K, Myint AM, Thuret S, Price J, Pariante CM. Interleukin- 1-beta: A new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. Neuropsychopharmacology. 2012;37:939-49.

52 | Centre for Stem Cells & Regenerative Medicine Professor Lucilla Poston FMedSci FRCOG Head of School of Life Course Sciences BSc (1975), PhD (1982)

Research interests My lab studies the consequences of maternal obesity and calorie- rich diets on the developing fetus. My laboratory was amongst the first to develop animal models that have shown that the offspring of obese rodents develop a predisposition to obesity, hypertension and insulin resistance at a young age. Recent work has suggested that endocrine influences on the developing hypothalamus may permanently affect hypothalamic function, including pathways affecting satiety and blood pressure control. In the clinic, my team have developed a complex intervention with the aim of improving pregnancy outcome and, potentially, reducing the risk of obesity in the child (the UPBEAT trial). In addition, I have a long standing interest in pre-eclampsia. Early on, I showed that endothelial dysfunction in maternal blood vessels plays a focal role in the disease, and that oxidative stress is likely to have a mechanistic function. Much of my present research effort is directed towards early biomarker discovery, which not only has benefit in terms of prediction of the disorder but also in identification of contributory causes.

Publications • Flynn AC, Begum S, White SL, Dalrymple K, Gill C, Alwan NA, Kiely M, Latunde-Dada G, Bell R, Briley AL, Nelson SM, Oteng-Ntim E, Sandall J, Sanders TA, Whitworth M, Murray DM, Kenny LC, Poston L. On Behalf Of The Scope and Upbeat consortiums OBOT. Relationships between maternal obesity and maternal and neonatal iron status. Nutrients. 2018;10(8). • Samuelsson AM, Clark J, Rudyk O, Shattock MJ, Bae SE, South T, Pombo J, Redington K, Uppal E, Coen CW, Poston L, Taylor PD. Experimental hyperleptinemia in neonatal rats leads to selective leptin responsiveness, hypertension, and altered myocardial function. Hypertension. 2013;62(3):627-33. • Poston et al. Developing a complex intervention for diet and activity behaviour change in obese pregnant women (the UPBEAT trial); assessment of behavioural change and process evaluation in a pilot randomised controlled trial. BMC Pregnancy Childbirth. 2013;13:148.

Centre for Stem Cells & Regenerative Medicine | 53 Dr S Tamir Rashid MRC Clinician Scientist, Senior Lecturer & Honorary Consultant Hepatologist Intercalated BSc / MBBS (1999 / 2002); MRes (2009); PhD (2011); MRCP (2006)

Research interests I am interested in studying how extracellular signals delivered via the complex eco-system surrounding hepatocytes (known as the hepatic ‘niche’) can be used to understand liver development, homeostasis and disease. Combining a unique collection of patient derived iPSCs with cutting edge tools in gene editing, 3-D tissue culture and animal models, we are generating ‘miniaturised-livers’ as a novel ex vivo approach to the study of several inherited and acquired liver pathologies. In the longer term, we plan to use these new constructs as an alternative source of transplant material for patients with liver failure.

Publications • Ong J, Serra MP, Segal J, Cujba AM, Ng SS, Butler R, Millar V, Hatch S, Zimri S, Koike H, Chan K, Bonham A, Walk M, Voss T, Heaton N, Mitry R, Dhawan A, Ebner D, Danovi D, Nakauchi H, Rashid ST. Imaging-based screen identifies laminin 411 as a physiologically relevant niche factor with importance for i-Hep applications. Stem Cell Rep. 2018;10(3):693-702. • Rashid ST, Humphries JD, Byron A, Dhar A, Askari JA, Selley JN, Knight D, Goldin RD, Thursz M, Humphries MJ. Proteomic analysis of extracellular matrix from the hepatic stellate cell line LX-2 identifies CYR61 and Wnt-5a as novel constituents of fibrotic liver. J Proteome Res. 2012;11:4052-4064. • Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu PQ, Paschon DE, Miranda E, Ordóñez A, Hannan NR, Rouhani FJ, Darche S, Alexander G, Marciniak SJ, Fusaki N, Hasegawa M, Holmes MC, Di Santo JP, Lomas DA, Bradley A, Vallier L. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature. 2011;478:391-394.

54 | Centre for Stem Cells & Regenerative Medicine Professor Steven Sacks Director, MRC Centre for Transplantation, School of Immunology & Microbial Sciences MB ChB, PhD, FRCP, FMedSci, FKC.

Research interests My research focuses on how the complement system affects the outcome of transplantation of solid organs, tissues and cells. I set up Complement UK to facilitate research translation and training in degenerative and other diseases. He has a longstanding interest in ethical regulation of research and has particular expertise of first-in-man studies. He has served policy on the advancement of health research through work with the Medical Research Council and Arthritis Research UK, and as a fellow of the Academy of Medical Sciences.

Publications • Sacks S, Nauser C, Howard M, Fanelli G, Farrar C. Collectin-11 (CL-11) is a major sentinel at epithelial surfaces and key pattern recognition molecule in complement-mediated ischaemic injury. Front Immunol. 2018;9:2023. • Fanelli G, Gonzalez-Cordero A, Gardner PJ, Peng Q, Fernando M, Kloc M, Farrar CA, Naeem A, Garred P, Ali RR, Sacks SH. Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress. Sci Rep. 2017;7(1):14625. • Farrar CA, Tran D, Li K, Wu W, Peng Q, Schwaeble W, Zhou W, Sacks SH. Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury. J Clin Invest. 2016;126(5):1911-25.

Centre for Stem Cells & Regenerative Medicine | 55 Professor Brian Salter Deputy Head of Department (Research) Professor of Politics PhD (1975)

Research interests A political scientist specialising in the analysis of public policy, I have studied the political forces at work in the policy arenas of education, health and, most recently, the life sciences. Here my work deals with the politics of new health technologies and the national and international governance issues associated with the global competition between nation states for innovative advantage in the knowledge economies of the future. Funded by the ESRC, I am currently exploring the governance challenges posed by the emergence of China, India and Brazil as the ‘Rising Powers’ in the global biomedical economy, focusing in particular on stem cell science and regenerative medicine. Closely associated with my academic work is my role as policy adviser to government, funding agencies, professional and international bodies and my contribution as ethical adviser to the European Framework Programmes. Between 2006 and 2011 I was a member of the national committee of the UK National Stem Cell Network.

Publications • Salter B and Salter C. Controlling new knowledge: genomic science, governance and the politics of bioinformatics. Soc Stud Sci. 2017;47(2):263-287. • Salter B, Zhou Y and Datta S. Governing new global health- care markets: the case of stem cell treatments. New Political Economy. 2017;22(1):76–91. http://www.tandfonline.com/ doi/full/10.1080/13563467.2016.1198757 • Salter B, Zhou Y, Datta S and Salter C. Bioinformatics and the politics of innovation in the life sciences: science and the state in the United Kingdom, China and India. Sci Technol Human Values. 2016;41(5):793–826.

56 | Centre for Stem Cells & Regenerative Medicine Dr Rocio Sancho Lecturer/Group Leader at CSCRM BSc /MSc (University of Cordoba, Spain 2001); PhD Inmunology (University of Cordoba, Spain 2004)

Research interests Our group is fascinated by the inherent plasticity of seemingly differentiated pancreatic cells and the molecular cues behind cell fate changes. My previous work uncovered a latent capacity for regeneration in the pancreas (Sancho et al, 2014-Cell Stem Cell), which could be harnessed to replace crucial insulin-producing cells lost to disease. Our main goal in the lab is to decipher the fundamental regulatory networks involved in pancreatic cell fate decisions using organoids and iPS cells, and to apply this knowledge to new strategies in regenerative medicine for diabetes.

Publications • Demcollari TI, Cujba AM, Sancho R. Phenotypic plasticity in the pancreas: new triggers, new players. Curr Opin Cell Biol. 2017;49:38-46. • Sancho R, Gruber R, Gu G, Behrens A. Loss of Fbw7 Reprograms Adult Pancreatic Ductal Cells into α, δ and β Cells. Cell Stem Cell. 2014;15(2):13953. • Sancho R*, Blake SM*, Tendeng C, Clurman BE, Lewis J, Behrens A. Fbw7 repression by hes5 creates a feedback loop that modulates notch-mediated intestinal and neural stem cell fate decisions. PLoS Biol. 2013;11(6). (*co-authors).

Centre for Stem Cells & Regenerative Medicine | 57 Professor Rosamund Scott Professor of Medical Law and Ethics; Co-Director, Centre of Medical Law and Ethics BA (Australian National University, Canberra); LLB (Corpus Christi College, Oxford); PhD (King’s College London), Barrister (LI)

Research interests My research interests largely concern the field of reproductive ethics and law. I have published on a wide range of ethical and legal topics in the area of reproduction, including ‘maternal-fetal conflict’, abortion, prenatal screening and diagnosis, selective abortion, preimplantation genetic diagnosis, ‘wrongful birth’, ‘wrongful life’, stem cell research and the donation of so-called ‘spare’ embryos to stem cell and other research. I am fortunate to have extensive involvement in interdisciplinary research projects with others.

Publications • Scott R and Wilkinson S. Germline genetic modification and identity: The mitochondrial and nuclear genomes. Oxford Journal of Legal Studies. 2017;p886-915. • Scott R. Risks, reasons and rights: the European convention on human rights and English abortion law. Med Law Rev. 2016;24(1):1-33. • Scott R, Williams C, Ehrich K, Farsides B. Donation of ‘spare’ fresh or frozen embryos to research: who decides that an embryo is ‘spare’ and how can we enhance the quality and protect the validity of consent? Med Law Rev. 2012;20(3):255-303. • Farsides B and Scott R. No small matter for some: practitioners’ views on the moral status and treatment of human embryos. Med Law Rev. 2012;20(1):90-107.

58 | Centre for Stem Cells & Regenerative Medicine Professor Paul Sharpe Dickinson Professor of Craniofacial Biology & Head of Department of Craniofacial Development and Stem Cell Biology BA (1974); PhD (1977)

Research interests I am interested in the role of Mesenchymal stem cells (MSCs) in tissue repair. The perivascular origin of MSCs that contribute to tissue repair is studied with a focus on the role of canonical Wnt signalling. In vivo epigenetic programming of perivascular MSCs as a mechanism of restricting differentiation following tissue damage is being investigated. I am also exploring stem cell niches in continuously growing teeth. The mouse incisor is continuously growing and mesenchymal stem cell niches are located in close proximity to each other in the proximal end of the incisor. Mouse genetic models are used to investigate the ‘architecture’ of the MSC niche and associated cell-cell interactions. MSCs have the ability to suppress T-cell proliferation. In vivo, this suppression is probably locally restricted to damage repair processes as a mechanism of limiting immune reactions during the initial phases of tissue repair. We study the mechanisms of in vitro suppression and their role in vivo in graft v host disease of humanised mouse models.

Publications • An Z, Sabalic M, Bloomquist RF, Fowler TE, Streelman T and Sharpe PT. A quiescent reservoir cell population replenishes a mesenchymal stem cell pool to drive accelerated growth in mouse incisors. Nat Commun. 2018;9(378). • Kaukua N, Shahidi MK, Konstantinidou C, Dyachuk V, Kaucka M, Furlan A, An Z, Wang L, Hultman I, Ahrlund-Richter L, Blom H, Brismar H, Lopes NA, Pachnis V, Suter U, Clevers H, Thesleff I, Sharpe P, Ernfors P, Fried K, Adameyko I. Glial origin of mesenchymal stem cells in a tooth model system. Nature. 2014;513(7519):551-4. • Zhao H, Feng J, Seidel K, Shi S, Klein O, Sharpe P, Chai Y. Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor. Cell Stem Cell. 2014;14(2):160-73.

Centre for Stem Cells & Regenerative Medicine | 59 Professor Christopher E Shaw FRCP FMedSci Professor of Neurology and Neurogenetics; Director, Maurice Wohl Clinical Neuroscience Institute MBChB (1984); MD (1997)

Research interests My clinical and research interest is elucidating the pathobiology of amyotrophic lateral sclerosis (ALS). My group was the first to discover mutations in TDP-43, FUS and TUBA4A in familial and sporadic ALS patients and show that they are toxic to neurons in a variety of cellular and animal models. We have demonstrated that iPSC derived neurons from ALS patients recapitulate key features of TDP-43 and FUS proteinopathies. We are performing detailed phenotyping of multiple ALS iPSC lines to map out pathogenic pathways and are working with industry to identify druggable targets and advance drug discovery.

Publications • So E, Mitchell JC, Memmi C, Chennell G, Vizcay-Barrena G, Allison L, Shaw CE, Vance C. Mitochondrial abnormalities and disruption of the neuromuscular junction precede the clinical phenotype and motor neuron loss in hFUSWT transgenic mice. Hum Mol Genet. 2018;27(3):463-474. • Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park IH, Friedman BA, Daley GQ, Wyllie DJ, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE, Chandran S. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP – 43 proteinopathies and reveal cell-specific vulnerability. Proc Natl Acad Sci U S A. 2012;109:5803-8. • Vance C, Rogelj B, Hortobágyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B1, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al- Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009;323:1208-11.

60 | Centre for Stem Cells & Regenerative Medicine Dr Tanya Shaw Senior Lecturer BSc (Hons, Physiology) from University of Western Ontario (1999); PhD (Cellular & Molecular Medicine) from University of Ottawa (2005)

Research interests Research in my lab focuses on the cellular and molecular mechanisms of wound healing in the skin and the ovaries. We are particularly interested in how tissue repair processes may go wrong, potentially resulting in pathological scars such as keloids on the skin or predisposing to cancer. As cell biologists, our focus is on cell plasticity and differentiation; when tissue is damaged many cell types in the vicinity of the wound will be activated and recruited and will change their characteristics in order to contribute to successful repair. We are interested in how these wound-induced cell differentiation events are epigenetically regulated and coordinated. Making use of in vitro and in vivo models, as well as human tissue, we hope to make headway in our understanding of wounds and scars, and to identify strategies to improve the healing process.

Publications • Shaw TJ, Zhang XY, Huo Z, Robertson D, Lovell PA, Dalgleish AG, Barton DP. Human peritoneal mesothelial cells display phagocytic and antigen-presenting functions to contribute to intraperitoneal immunity. Int J Gynecol Cancer. 2016;26(5):833-8. • Shaw TJ, Martin P. Wound repair: a showcase for cell plasticity and migration. Curr Opin Cell Biol. 2016;42:29-37. • Fitzgerald O’Connor EJ, Badshah II, Addae LY, Kundasamy P, Thanabalasingam S, Abioye D, Soldin M, Shaw TJ. Histone deacetylase (HDAC) 2 is up-regulated in normal and keloid scars. J Invest Dermatol. 2012;132(4):1293-6.

Centre for Stem Cells & Regenerative Medicine | 61 Professor Chi Wai ‘Eric’ So Chair in Leukaemia Biology PhD

Research interests The primary goal of my research program is to characterise the mechanisms of transcriptional regulation that are corrupted in leukemia. By identification and molecular dissection of the transcriptional and epigenetic networks deregulated by oncogenic transcription factors we hope to gain important mechanistic insights into the molecular basis of the diseases, and in longer term, provide fruitful avenues for development of specific therapeutic interventions.

Publications • Siriboonpiputtana T, Zeisig BB, Zarowiecki M, Fung TK, Mallardo M, Tsai CT, Lau PNI, Hoang QC, Veiga P, Barnes J, Lynn C, Wilson A, Lenhard B, So CWE. Transcriptional memory of cells of origin overrides β-catenin requirement of MLL cancer stem cells. EMBO J. 2017;36(21):3139-3155. • Fung TK, Leung AY, So CW. Sox4you: a new player in C/ EBP-alpha leukemia. Cancer Cell. 2013;24(5):557-9. • Arteaga MF, Mikesch JH, Qiu J, Christensen J, Helin K, Kogan SC, Dong S, So CW. The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia. Cancer Cell. 2013;23(3):376-89.

62 | Centre for Stem Cells & Regenerative Medicine Dr Rita Sousa-Nunes Cancer Research UK Career Development Fellow (Tenure-track Principal Investigator) PhD (National Institute for Medical Research / University College London, 2004)

Research interests My major research interest is control of neural stem cell (NSC) proliferation in development, adulthood and disease. We address mechanisms of asymmetric cell division, balance of proliferation versus differentiation, quiescence (reversible) versus termination (irreversible), and temporal progression of progenitors. We enquire into cell-autonomous and non-autonomous regulation of these properties and how some or all of the above differ in malignant NSCs. We mainly use the fruitfly Drosophila melanogaster as a model but, concerning quiescence, we are performing comparative studies with mouse NSCs in vitro and are starting to perform our first analyses of human samples. Concerning temporal progression, Drosophila NSCs have an ‘internal timer’, consisting of the sequential expression of a small number of transcription factors. A fascinating question is whether this is conserved in mammalian NSCs.

Publications • Shaw RE, Kottler, B, Ludlow ZN, Buhl E, Kim S, Morais da Silva S, Miedzik A, Coum A, Hodge JJL, Hirth F, Sousa-Nunes R. In vivo expansion of functionally integrated GABAergic interneurons by targeted increase of neural progenitors. EMBO J. 2018;37(13). • Sousa-Nunes R, Somers WG. Mechanisms of asymmetric progenitor divisions in the Drosophila central nervous system. Adv Exp Med Biol. 2013;786:79-102. • Sousa-Nunes R, Yee LL, Gould AP. Fat cells reactivate quiescent neuroblasts via TOR and glial Insulin relays in Drosophila. Nature. 2011;471:508-12.

Centre for Stem Cells & Regenerative Medicine | 63 Dr Francesca Spagnoli Reader and Group Leader at the Centre for Stem Cell and Regenerative Medicine MD (La Sapienza, University of Rome, IT); PhD (UPMC and Pasteur Institute, Paris, FR)

Research interests Cell identities are assigned by the interplay of extrinsic signals and intrinsic determinants. My main research interest is in understanding the mechanisms regulating cell identity and plasticity of key metabolic organs, such as the pancreas and the liver. We use a combination of genetic approaches with genomic strategies and imaging in mouse embryos and human stem cells to study how distinct cell types, such as liver and pancreas, arise from common progenitors and acquire specialized shape to form functional organs. What is the gene regulatory network upstream of the fate decision between liver and pancreas? Is the establishment of distinct cellular identities and morphogenetic programs interdependent? How plastic are these cellular states? Can we harness cell plasticity between liver and pancreas towards novel regenerative therapies for diabetes? Ultimately, the long- term goal of our research is to translate these concepts into a better understanding of the pathogenesis as well as treatment options of diabetes.

Publications • Naumann, H, Rathjen, T, Poy, MN, Spagnoli FM. The RhoGAP Stard13 controls insulin secretion through F-actin remodeling. Mol Metab. 2018;8:96-105. • Cerdá-Esteban N, Naumann N, Ruzzittu S, Cozzitorto C, Pongrac IM, Hommel A, Mah N, Andrade-Navarro MA, Bonifacio E, Spagnoli FM. Step-wise reprogramming of liver to pancreas progenitor state by the transcriptional regulator Tgif2. Nat Commun. 2017;8(1412). • Rodríguez-Seguel E, Mah N, Naumann H, Pongrac IM, Cerdá- Esteban N, Fontaine JF, Wang Y, Chen W,Andrade-Navarro MA, Spagnoli FM. Mutually exclusive signaling signatures define the hepatic and pancreatic progenitor cell lineage divergence. Genes Dev. 2013;27:1932-46.

64 | Centre for Stem Cells & Regenerative Medicine Professor Karen Steel Professor of Sensory Function BSc (University of Leeds, 1974), PhD (UCL, 1978)

Research interests I study the genetics of deafness, using the mouse as a model to identify the genes involved and to understand the underlying molecular, cellular and physiological mechanisms. We use a very broad range of approaches including positional cloning to identify causative mutations, ultrastructural and genome – wide expression studies, developmental analysis, and electrophysiological measures of hearing function. We identified the first mouse gene involved in deafness, Myo7a; this and many other mouse deafness genes we have characterised also underlie human deafness. While at the Wellcome Trust Sanger Institute I established a large scale programme to generate new mouse mutants from targeted ES cells and screen them for key signs of disease. Over 1,000 new mutant lines have now been generated and screened, revealing 30 new and unexpected genes underlying deafness. These new deaf mutants are available to follow up and characterise the multiple different ways that auditory function can be affected.

Publications • Bowl MR, Simon MM, Ingham NJ, Greenaway S, Santos L, Cater H, Taylor S, Mason J, Kurbatova N, Pearson S, Bower LR, Clary DA, Meziane H, Reilly P, Minowa O, Kelsey L; International Mouse Phenotyping Consortium, Tocchini- Valentini GP, Gao X, Bradley A, Skarnes WC, Moore M, Beaudet AL, Justice MJ, Seavitt J, Dickinson ME, Wurst W, de Angelis MH, Herault Y, Wakana S, Nutter LMJ, Flenniken AM, McKerlie C, Murray SA, Svenson KL, Braun RE, West DB, Lloyd KCK, Adams DJ, White J, Karp N, Flicek P, Smedley D, Meehan TF, Parkinson HE, Teboul LM, Wells S, Steel KP, Mallon AM, Brown SDM. A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction. Nat Commun. 2017;8(1):886. • Chen J, Ingham N, Kelly J, Jadeja S, Goulding D, Pass J, Mahajan VB, Tsang SH, Nijnik A, Jackson IJ, White JK, Forge A, Jagger D, Steel KP. Spinster homolog 2 (spns2) deficiency causes early onset progressive hearing loss. PLoS Genet. 2014;10(10):e1004688. • White JK, Ingham, NJ, 28 others, Watt, FM, Steel KP. Genome- wide generation and systephenotyping of knockout mice reveals new roles for many genes. Cell. 2013;154(2):452-64.

Centre for Stem Cells & Regenerative Medicine | 65 Professor Andrea Streit Professor of Developmental Neurobiology BSc (University of Cologne); PhD (University of Heidelberg, 1990)

Research interests Relating to the outside world relies on functional sense organs, which provide visual, auditory and olfactory input. Our research aims to understand how cells transit from a pluripotent state to definitive sensory progenitors and are subsequently specialised as ear, eye and olfactory system. We combine in vivo experiments with molecular and bioinformatics approaches to uncover the gene networks that underlie these processes. A second aspect of our research focuses on regeneration of sensory cells in the inner ear. Specifically, we explore the epigenetic mechanisms that prevent hair cell regeneration in the mammalian cochlea.

Publications • Ahmed M and Streit A. Lsd1 interacts with cMyb to demethylate repressive histone marks and maintain inner ear progenitor identity. Development. 2018;145(4):1-9. • Chen J, Tambalo M, Barembaum M, Ranganathan R, Simões- Costa M, Bronner ME, Streit A. A systems level approach reveals new gene regulatory modules in the developing ear. Development. 2017;144:1531-1543. • Lleras-Forero L, Tambalo M, Christophorou N, Chambers D, Houart C, Streit A. Neuropeptides: developmental signals in placode progenitor formation. Dev Cell. 2013;26:195-203.

66 | Centre for Stem Cells & Regenerative Medicine Dr Sandrine Thuret Head of the Neurogenesis and Mental Health Laboratory, Senior Lecturer in Neural Stem cells and Head of the Cells and Behaviour Unit BSc (1994); MSc (1997); MSc (1998); PhD (2002)

Research interests My lab explores the mechanisms regulating adult hippocampal neurogenesis (AHN) and their role in mental health. The adult mammalian brain contains small populations of neural stem cells dividing and differentiating into neurons. This process of neurogenesis occurs in the hippocampus. AHN decreases with age and stress whereas increased AHN is linked to improved memory and mood. Therefore, AHN emerges as a target for counteracting the effect of ageing and stress and thus preventing cognitive and mood decline. We investigate the molecular mechanisms governing neurogenesis by using human hippocampal cell lines and the mouse as a model to study cognition and mood. We are currently studying the molecular mechanisms by which interventions (i.e. diet, antidepressants) and diseases (i.e. Alzheimer’s Disease, depression) impact on AHN and subsequently affect cognition and mood.

Publications • Egeland M, Guinaudie C, Du Preez A, Musaelyan K, Zunszain PA, Fernandes C, Pariante CM, Thuret S. Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression. Transl Psychiatry. 2017;7(4):e1101. • Powell TR, Murphy T, Lee SH, Duarte RRR, Lee HA, Smeeth D, Price J, Breen G, Thuret S. Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood. Sci Rep. 2017;7(1):15112. • Murphy T, Thuret S. The systemic milieu as a mediator of dietary influence on stem cell function during ageing. Ageing Res Rev. 2015;19:53-64.

Centre for Stem Cells & Regenerative Medicine | 67 Professor Abigail Tucker Professor of Development & Evolution BA Hons Oxford 1992; DPhil Oxford 1996

Research interests My lab is interested in development of the head, with particular focus on development and regeneration/repair of the ear, jaw and dentition. Formation of these structures involves complex epithelial- mesenchymal interactions. I am interested in how pattern and shape are controlled, and the influence of embryonic origin on function. We research how organs form during normal development and what goes wrong in the case of congenital birth defects. We are currently studying stem/progenitor cells in the ear and their role during repair of the tympanic membrane. We are also studying the role of stem cells in renewal of tooth germs in animals that continuously replace their teeth, investigating how developmental pathways are utilized during regeneration. The other main focus of the lab is how evolution shapes our faces and how developmental biology can be used to understand the mechanisms behind evolutionary change. The lab is therefore a host to many different species for study, including snakes, lizards, chicks, opossums, and mice.

Publications • Anthwal N, Urban DJ, Luo Z-X, Sears KE, Tucker AS. Meckel’s cartilage breakdown offers clues to mammalian middle ear evolution. Nat Ecol Evol. 2017;1(4):93. • Fuchs JC, Linden JF, Baldini A, Tucker AS. An early defect in myogenesis causes Otitis Media in two mouse models of 22q11.2 deletion syndrome. Hum Mol Genet. 2015;24:1869-19882. • Thompson H, Tucker AS. Dual origin of the epithelium of the middle ear. Science. 2013;339:1453-1456.

68 | Centre for Stem Cells & Regenerative Medicine Dr Alessandra Vigilante Lecturer PhD in Bioinformatics and Computational Biology (2012, University of Naples Federico II, Italy)

Research interests My research interests lie in genomics and computational biology. My current research is exploring how genetic variation between cells impacts on their phenotypic behavior in culture. I also aim to understand how disease-associated mutations impact on cell behavior. In fact, what appears to be the same disease can be caused by mutations in many different genes. Conversely, many different mutations can occur in the same gene, producing clinical consequences that vary across patients. A key objective of research in our group is to integrate genomic data from large- scale population-based health research studies that will give access to genetic variants associated with a wide variety of human conditions. The generation of disease-relevant cell types will help us to understand how the variants impact cell behaviors. The link to extensive clinical disease-related information from NHS data will allow correlations between genetic and health records.

Publications • Vigilante A, Laddach A, Moens N, Meleckyte R, Leha A, Ghahramani A, Culley OJ, Kathuria A, Hurling C, Vickers A, Wiseman E, Tewary M, Zandstra PW; HipSci Consortium, Durbin R, Fraternali F, Stegle O, Birney E, Luscombe NM, Danovi D, Watt FM. Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors. Cell Rep. 2019;26(8):2078-2087. • Sugimoto Y, Vigilante A, Darbo E, Zirra A, Militti C, D’Ambrogio A, Luscombe NM, Ule J. hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1. Nature. 2015;519(7544):491-4. • Tajik M*, Vigilante A*, Braun S, Hänel H, Luscombe NM, Ule J, Zarnack K, König J. *equal contributions. Intergenic Alu exonisation facilitates the evolution of tissue-specific transcript ends. Nucleic Acids Res. 2015;43(21):10492-505.

Centre for Stem Cells & Regenerative Medicine | 69 Dr Fiona Wardle Lecturer in Cardiovascular Development BA (University of Cambridge, 1994); PhD (UCL, 1998)

Research interests We are interested in the transcriptional networks that control gene expression as cells move from being pluripotent to become specified and subsequently differentiated into different tissues and organs. We combine genomics and proteomics techniques with experimental work in zebrafish embryos and embryonic stem cells to characterize these transcriptional networks, with a particular focus on mesoderm and endoderm cells, which will go on to form organs such as the heart and pancreas, respectively.

Publications • Nelson AC, Cutty SJ, Gasiunas SN, Deplae I, Stemple DL, Wardle FC. In vivo regulation of the zebrafish endoderm progenitor niche by T-Box transcription factors. Cell Rep. 2017;19(13):2782-2795. • Nelson AC, Cutty SJ, Niini M, Stemple DL, Flicek P, Houart C, Bruce AE, Wardle FC. Global identification of Smad2 and Eomesodermin targets in zebrafish identifies a conserved transcriptional network in mesendoderm and a novel role for Eomesodermin in repression of ectodermal gene expression. BMC Biol. 2014;12:81. • Nelson AC, Pillay N, Henderson S, Presneau N, Tirabosco R, Halai D, Berisha F, Flicek P, Stemple DL, Stern C, Wardle FC, Flanagan AM. An integrated functional genomics approach identifies the regulatory network directed by brachyury (T) in chordoma. J Pathol. 2012;228(3):274-85.

70 | Centre for Stem Cells & Regenerative Medicine Professor Fiona M Watt FRS FMedSci Director – Centre for Stem Cells and Regenerative Medicine BA (University of Cambridge, 1976); DPhil (University of Oxford, 1979)

Research interests My major research interest is in the role of stem cells in adult tissue maintenance. For many of our studies we use mammalian epidermis as a model system, both in the context of genetically modified mice and epidermal reconstitution in culture. Current projects are exploring self-renewal and lineage selection by human and mouse epidermal stem cells, the role of stem cells in epidermal and oral tumour formation, and the nature of mesenchymal cells in skin. We have active collaborations with bioengineers and chemists in order to study stem cell-niche interactions in vitro. We are also collaborating with bioinformaticians and computational biologists who are helping us to explore stem cell heterogeneity at single cell resolution.

Publications • Liakath-Ali K, Mills EW, Sequeira I, Lichtenberger BM, Pisco AO, Sipilä KH, Mishra A, Yoshikawa H, Wu CC, Ly T, Lamond AI, Adham IM, Green R, Watt FM. An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis. Nature. 2018;556(7701):376-380. • Kilpinen H, Goncalves A, Leha A, Afzal V, Alasoo K, Ashford S, Bala S, Bensaddek D, Casale FP, Culley OJ, Danecek P, Faulconbridge A, Harrison PW, Kathuria A, McCarthy D, McCarthy SA, Meleckyte R, Memari Y, Moens N, Soares F, Mann A, Streeter I, Agu CA, Alderton A, Nelson R, Harper S, Patel M, White A, Patel SR, Clarke L, Halai R, Kirton CM, Kolb-Kokocinski A, Beales P, Birney E, Danovi D, Lamond AI, Ouwehand WH, Vallier L, Watt FM, Durbin R, Stegle O, Gaffney DJ. Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs. Nature. 2017;546(7660):370-375. • Driskell, RR, Lichtenberger BM, Hoste E, Kretzschmar, K, Simons, BD, Charalambous, M, Ferron, SR, Herault, Y, Pavlovic, G, Ferguson-Smith, AC. and Watt FM. Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature. 2013;504(7479):277-281.

Centre for Stem Cells & Regenerative Medicine | 71 Professor Qingbo Xu BHF John Parker Chair of Cardiovascular Sciences MD (Innsbruck University, Austria); PhD (Peking Union Medical College)

Research interests My research interest is in the field of vascular regeneration in vascular disease. We have discovered the presence of stem/ progenitor cells in the adventitia of the vessel wall that have the ability to differentiate into endothelial or smooth muscle cells. To clarify how a stem cell becomes a vascular cell our group is studying the mechanisms of stem cell differentiation into vascular lineages. We have identified several crucial genes localised in the nucleus that play a key role. Our group is also studying the contribution of stem/progenitor cells to the pathogenesis of atherosclerosis, clarifying the mechanisms of stem cell differentiation into endothelial and smooth muscle cells, and testing a potential use of stem cell therapy for the vascular disease.

Publications • Issa Bhaloo S, Wu Y, LE Bras A, Yu B, Gu W, Xie Y, Deng J, Wang Z, Zhang Z, Kong D, Hu Y, Qu A, Zhao Q, Xu Q. Binding of dickkopf-3 to CXCR7 enhances vascular progenitor cell migration and degradable graft regeneration. Circ Res. 2018;123(4):451-466. • Karamariti E, Margariti A, Winker B, Wang X, Hong X, Baban D, Ragoussis J, Huang Y, Han JD, Wong MM, Sag CM, Shah AM, Hu Y, Xu Q. Smooth muscle cells differentiated from reprogrammed embryonic lung fibroblasts through DKK3 signaling are potent for tissue engineering of vascular grafts. Circ Res. 2013;112(11):1433-43. • Margariti A, Winkler B, Karamariti E, Zampetaki A, Tsai T, Baban D, Ragoussis J, Huang Y, Han JJ, Zeng L, Hu Y, and Xu Q. Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelization in tissue- engineered vessels. Proc Natl Acad Sci USA. 2012;109:13793-8.

72 | Centre for Stem Cells & Regenerative Medicine Professor Peter Zammit Professor of Cell Biology in the Randall Division of Cell and Molecular Biophysics BSc (King’s College London, 1987); PhD (1992); Postgraduate College Certificate of Academic Practice (2007)

Research interests My core research is to understand how muscle stem cells are regulated in healthy, aged and diseased skeletal muscle: an archetypal adult stem cell model in which maintenance, growth and repair of functionally specialised post-mitotic cells is achieved by recruitment of undifferentiated precursors. The resident stem cells of skeletal muscle, satellite cells, are activated to undergo extensive proliferation to generate myoblasts that then differentiate to provide new myonuclei for muscle fibres. This normally efficient mechanism gradually fails in muscle wasting diseases, such as muscular dystrophies. We are investigating transcriptional and signalling pathways that control satellite cells, and the contribution of satellite cell dysfunction to Emery-Dreifuss muscular dystrophy, Fascioscapulohumeral muscular dystrophy and cancer, such as rhabdomyosarcoma.

Publications • Banerji CRS, Panamarova M, Hebaishi H, White RB, Relaix F, Severini S and Zammit PS. PAX7 target genes are globally repressed in FSHD skeletal muscle. Nat. Commun. 2017;8:2152. Sun C, De Mello V, Mohamed A, Ortuste Quiroga HP, Garcia- Munoz A, Al Bloshi A, Tremblay AM, von Kriegsheim A, Collie-Duguid E, Vargesson N, Matallanas D, Wackerhage H and Zammit PS. Common and distinctive functions of the Hippo effectors Yap and Taz in muscle stem cell function. Stem Cells. 2017;35:1958–1972. • Ono Y, Urata Y, Goto S, Nakagawa S, Humbert PO, Li T.-S, Zammit PS. Muscle stem cell fate is controlled by the cell polarity protein Scrib. Cell Rep. 2015;10,1135–1148.

Centre for Stem Cells & Regenerative Medicine | 73 The four Thames-side campuses of King’s, located within a single square mile in the heart of London, together with the Denmark Hill Campus in south London.

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BORN HOLBO Intercollegiate Halls OL C RN H H L Guy’s

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NC T N TREE HIG E RD S E Campus XFO H R O C D W

D TRAN CIT

WES T END L S A Orchard Lisle House LL ADI KENSINGTON HDE C Iris Brook House C rbanest GARDENS PARK PI T Tower Bridge ST S HOLLAND GREEN ST THOMAS JAMES’S W H PARK PARK A IG PARK TER H ST

L E OO R

C

A

WES TMINS TER L D OUGH Wolfson House A R P O H B T D

E A

B Great Dover Street St Thomas’ O

M R

The Defence Studies Department A OAD Apartments L R

D A Campus LAMBETH provides academic support to the O R Moonraker Point ’S

UK Joint Services Command and G N I K Julian Markham

Stamford Street

House

OVAL Apartments

based at Shrivenham, Wiltshire. W

A

L W Ewen Henderson Court between Oxford and Swindon; the O R Waterloo

T nearest railway station is Swindon. H Campus BATTERSEA R PARK O A

D PECKHAM R OAD D A DE O S R RESPIGNK CHEL SEA C PAR E M A Denmark Hill M PH Campus A CLA H T L L DEN MARK I R PECKHAM RE V E H R I HILL K COMMON R A

RUSKIN M PARK N CLAPHAM E D

Champion Hill COMMON

Residence

WANDS W O R T H BROCKWELL PARK

74 | Centre for Stem Cells & Regenerative Medicine R I V E R T H A M E S

SMOKING IS NOT PERMITTED ON KING’S CAMPUSES OR PREMISES

City Pier London Bridge Duke Street Hill London Bridge

5 Tooley B edale LONDON St 3 BRIDGE reet St reet

4 St Thomas 7 Lavington Street S (closed until 2018) (10 minute walk) treet reet Southwark St 6 3 eet Joiner Street B 1 L Street A tainer Str S

ston

eet r We St 8 6 H K E

ough High M 7 1 r I St Thomas St

Bo Nag’s Hea ond 9 e P re d Yard F et Ne w 8 2 Streetcomen G at Maz e 2 Melior KING’S COLLEGE LONDON 4 Gr J C Str eet A Boland House, enniseet T tr D Science Gallery London S 5

B Chapel K i

Place p l

y i C Doyle’s House n Snowsfields g

osb ow Bowling Green R S Cr t D Greenwood Theatre r

Britannia House e e

E Henriette Raphael House (8 minute walk) t POINTS OF INTEREST F Hodgkin Building GUY’S HOSPITAL Main entrance 1 Statue of Thomas Guy G New Hunt’s House - 1 Bermondsey Wing Parenting Room Other entrance 2 Guy’s Memorial Arch 2 Borough Wing H Shepherd’s House Disabled access 3 Southwark Cathedral 3 Conybeare House I Wolfson Centre for Assisted disabled access 4 Borough Market 4 Age-Related Diseases Secure bike shed* 5 Hay’s Galleria 5 The Cancer Centre J Wolfson House Shuttle bus stop 6 The Shard 6 Southwark Wing K Addison House * You must register with Security at the 7 Old Operating Theatre 7 Tower Wing Hodgkin Building in order to have access L KCLSU Hub, The Shed 8 Gordon Museum and Guy’s Bar 8 Counting House M Premier Inn and King’s and medical public only) Sport, Health and Fitness 9 Memorial Gardens Centre

Centre for Stem Cells & Regenerative Medicine | 75 King’s College London Centre for Stem Cells and Regenerative Medicine 28th floor, Tower Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT

+44 (0)20 7188 5604 [email protected] www.kcl.ac.uk