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Lewis-McDougall Lab

 

Heart disease is one of the main causes of death in the UK and worldwide. At present no widely available, restorative option exists therefore new strategies are required to identify a safe and efficient way of treating heart failure.

In recent years, stem cells have emerged as a potentially valuable tool for the repair of damaged hearts. In particular a breakthrough discovery, which identified that stem cells could be generated from a patient's own skin cells, termed induced pluripotent stem cells (iPSCs). iPSCs have gained increasing recognition given their ability to generate new, patient-specific, cardiac muscle cells, which when delivered into damaged hearts improve cardiac function. 

The focus of Dr Lewis-McDougall's research aims to understand the influence of donor age/disease on iPSC potential, identify the optimal iPSC progeny for cardiac repair and investigate extracellular vesicles as mediators of cardiac repair.

RESEARCH OVERVIEW

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Fiona Lewis-McDougall

Group Leader

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I completed a PhD in Stem Cells and Regenerative Medicine from the University of Southampton, 

My current research aims to investigate the therapeutic potential of human induced pluripotent stem cell-derived cardiac progenitor cells (hiPSCs-CPCs) and to directly compare with endogenous cardiac progenitor cells (eCPCs) from the same patients.

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Dr Alia Gasim

Postdoctoral Researcher

GROUP MEMBERS

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Dr Sammy El Mansi

Postdoctoral Researcher

I am interested in the immunological consequences of a single nucleotide polymorphism within the ACKR1 gene which is prevalent in African populations.

Dr Caroline Anderson

Postdoctoral Researcher

Dr Maryna Samus

Postdoctoral Researcher

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My research aims to understand the role of atypical chemokine receptors in the alteration of the immune system and subsequent impacts on tumour growth and progression.

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Currently recruiting!

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I have a BSC and MsC in Biochemistry (Ugent,Belgium), MRes in Cardiac and Vascular medicine (QMUL)

Research

Improving stem cell therapy for ischaemic heart failure

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Laura Deelen

PhD Student

My PhD is focused on investigating the expression and function of ACKR4 in the heart. My work aims to characterise localisation and cell type expression of ACKR4, as well as its effect on heart function and health.

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Stefan Russo

PhD Student

Background:

Physician Surgeon (UNAM, Mexico); MSc. Regenerative Medicine (QMUL, London) 

Current research:

Exosomes and biomaterials for heart failure. Other interests: Immunology, 3D printing, patient specific implants & biofabrication.

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Dr Esteban Ortega

PhD Student

I am a Cardiology SpR based at Barts Hospital and am currently undertaking a PhD investigating the efficacy of stem-cell therapy in patients with DCM.

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Dr Mohsin Hussain

PhD Student

GROUP ALUMNI

Fields of research interest:

Tissue engineering, stem cell therapy

 

Research:

Biomaterials design for epicardial placement of mesenchymal stem cells for the treatment of myocardial infarction 

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Yaqi You

PhD Student

Graduate of The University of Aberdeen (BSc Sport & Exercise Science) and Queen Mary University of London (MRes Inflammation) with an interest in the role of M2-like macrophages in cardiac repair after myocardial infarction.

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GROUP ALUMNI

Mihai Podaru

PhD Student

RECENT PUBLICATIONS

Reparative macrophage transplantation for myocardial repair: a refinement of bone marrow mononuclear cell-based therapy

Basic Research in Cardiology, 2019 (114; 34)

Podaru MN, Fields L, Kainuma S, Ichihara Y, Hussain M, Ito T, Kobayashi K, Mathur A, D'Acquisto F, Lewis-McDougall F and Suzuki K

On-site fabrication of Bi-layered adhesive mesenchymal stromal cell-dressings for the treatment of heart failure

Biomaterials, 2019 (209; 41-53)

Kobayashi K, Ichihara Y, Sato N, Umeda N, Fields L, Fukumitsu M, Tago Y, Ito T, Kainuma S, Podaru M, Lewis-McDougall F, Yamahara K, Uppal R and Suzuki K

Aged‐senescent cells contribute to impaired heart regeneration

Ageing Cell, 2019 (18; e12931)

Lewis‐McDougall FC, Ruchaya PJ, Domenjo‐Vila E, Teoh TS, Prata L, Cottle BJ, Clark JE, Punjabi PP, Awad W, Torella D, Tchkonia T, Kirkland JL and Ellison‐Hughes GM

Non-invasive strategies for stimulating endogenous repair and regenerative mechanisms in the damaged heart

Pharmacological Research, 2018 (127; 33-40)

Lewis FC, Kumar SD and Ellison-Hughes GM

Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

JACC: Basic to Translational Science, 2017 (2; 717-736)

Lewis FC, Cottle BJ, Shone V, Marazzi G, Sassoon D, Tseng CCS, Dankers PYW, Chamuleau SAJ, Nadal-Ginard B and Ellison-Hughes GM

Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification

Cell Death & Differentiation, 2017 (24; 2101-2116)

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 CM, Britti D, Veltri P, Indolfi C, Nadal-Ginard B, Ellison-Hughes GM and Torella D

Active GSK3β and an intact β-catenin TCF complex are essential for the differentiation of human myogenic progenitor cells

Scientific Reports, 2017 (7; 13189)

Agley CC, Lewis FC, Jaka O, Lazarus NR, Velloso C, Francis-West P, Ellison-Hughes GM and Harridge SDR

Skeletal muscle-derived interstitial progenitor cells (PICs) display stem cell properties, being clonogenic, self-renewing, and multi-potent in vitro and in vivo

Stem Cell Research & Therapy, 2017 (8; 158)

Cottle BJ, Lewis FC, Shone V and Ellison-Hughes GM

Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart

Nature Protocols, 2014 (7; 1662-81)

Smith AJ, Lewis FC, Aquila I, Waring CD, Nocera A, Agosti V, Nadal-Ginard B, Torella D and Ellison GM

Porcine skeletal muscle-derived multipotent PW1pos/Pax7neg interstitial cells: isolation, characterization, and long-term culture

Stem Cells Translational Medicine, 2014 (3; 702-712)

Lewis FC, Henning BJ, Marazzi G, Sassoon D, Ellison GM and Nadal-Ginard B

Carbonic Anhydrase Activation Is Associated With Worsened Pathological Remodeling in Human Ischemic Diabetic Cardiomyopathy

Journal of the American Heart Association, 2014 (3; e000434)

Torella D, Ellison GM, Torella M, Vicinanza C, Aquila I, Iaconetti C, Scalise M, Marino F, Henning BJ, Lewis FC, Gareri C, Lascar N, Cuda G, Salvatore T, Nappi G, Indolfi C, Torella R, Cozzolino D and Sasso FC

You can see our full publication list here. If you cannot access any of our papers, please do contact us, we would be happy to share a copy.

LATEST NEWS

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Induced pluripotent stem cells regenerative potential in cardiovascular disease

Funded by Barts Charity

IPSCs have been successfully generated from different aged donors however evidence suggests that aged cells generate iPSCs at lower efficiency and may have deteriorated functions making them unsuitable for clinical application. Aging is determined not only by chronological age but also by health condition therefore rigorous testing of iPSCs derived from aged, cardiovascular disease patients is required to provide a clear indication on their suitability for clinical application. This project seeks to identify key ageing molecular signatures and uncover their association with cellular reprogramming in order to select optimal iPSCs for cardiac regenerative therapies.

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Therapeutic potential of human induced pluripotent stem cell-derived cardiac progenitor cells: Direct comparison with endogenous cardiac progenitor cells from the same patients

Funded by The British Heart Foundation

The optimal iPSC progeny for cardiac repair is currently unknown and to date the majority of iPSC studies for cardiac repair have focused on generating fully differentiated iPSC-cardiomyocytes. While this approach has shown some promise, a major drawback is that only a single replacement cell type is delivered to the heart. Furthermore, iPSC-cardiomyocytes display an immature phenotype and their integration with the host myocardium often leads to arrhythmias.

As endogenous cardiac progenitor cells (eCPCs) have been widely reported to possess reparative characteristics the generation of human iPSC-CPCs offers an alternative source of renewable precursors where isolation of resident CPCs is not feasible. Given that there is currently much discussion regarding the cardiac regenerative capacity of c-kit+ eCPCs, which is largely based on observations using rodent models, in this project we will directly compare human c-kit+ eCPCs and iPSC-CPCs isolated from the same patients to provide vital information and address the therapeutic potential of this population.

CURRENT PROJECTS

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