skip to content

Cambridge Cardiovascular

 

Research

I have joined Dr Sanjay Sinha's team in 2014 to improve our understanding of human epicardial development. My project aims to characterise the heterogeneity of the epicardial cells in humans and to decode their commitment to different cardiovascular compartments. 

The epicardium has been shown in animal models to produce coronary vascular smooth muscle cells and cardiac fibroblasts but it is unclear whether epicardium is also able to supply coronary endothelial cells and cardiomyocytes. Our team has the capability to generate human epicardium in vitro from ES and IPS cells, and I propose to compare this engineered epicardium to embryonic and adult epicardium harvested from human samples.

I strive to validate this engineered epicardium as a model of development, a source of cells for cell therapy and a platform for drug discovery/testing in the context of cardiac regenerative medicine. Moreover, my project is expected to advance our understanding of the origin and development of the coronary vessels in humans, which would help to apprehend the coronary vascular diseases.

Publications

Key publications: 

A novel human PSC-derived neural crest model of Treacher Collins Syndrome shows defects in cell death and migration. Serrano F, Bernard W, Granata A, Iyer D, Steventon B, Kim M, Vallier L, Gambardella L and Sinha S. Stem Cells & Dev2018 Jan 15; 28(2): 81-100.

Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs. Bertero APawlowski MOrtmann DSnijders KYiangou LCardoso de Brito MBrown SBernard WGCooper JDGiacomelli E, Gambardella LHannan NR, Iyer DSampaziotis FSerrano FZonneveld MCSinha SKotter MVallier L. Development. 2016 Dec;143(23):4405-4418

Embryological Origin of Human Smooth Muscle Cells Influences Their Ability to Support Endothelial Network Formation. Bargehr J, Low L, Cheung C, Bernard WG, Iyer D, Bennett MR, Gambardella L, Sinha S. Stem Cells Transl Med. 2016 Jul;5(7):946-59.

Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells. Iyer D, Gambardella L, Bernard WG, Serrano F, Mascetti VL, Pedersen RA, Talasila A, Sinha S. Development. 2015 Apr 15;142(8):1528-41. doi: 10.1242/dev.119271. Epub 2015 Mar 26. Erratum in: Development. 2016 Mar 1;143(5):904.

The regulatory subunits of PI3Kγ control distinct neutrophil responses. Deladeriere A, Gambardella L, Pan D, Anderson KE, Hawkins PT, Stephens LR. Sci Signal. 2015 Jan 20;8(360):ra8.

P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils. Damoulakis G, Gambardella L, Rossman KL, Lawson CD, Anderson KE, Fukui Y, Welch HC, Der CJ, Stephens LR, Hawkins PT. J Cell Sci. 2014 Jun 1;127(Pt 11):2589-600.

Molecular players in neutrophil chemotaxis--focus on PI3K and small GTPases. Gambardella L, Vermeren S. J Leukoc Biol. 2013 Oct;94(4):603-12.

Phosphoinositide 3-OH kinase regulates integrin-dependent processes in neutrophils by signaling through its effector ARAP3. Gambardella L, Anderson KE, Jakus Z, Kovács M, Voigt S, Hawkins PT, Stephens L, Mócsai A, Vermeren S. J Immunol. 2013 Jan 1;190(1):381-91.

Quantitative analysis of angiogenesis in the allantois explant model. Gambardella L, Zudaire E and Vermeren S (2012).  In The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications, Springer Netherlands.189-204

A computational tool for quantitative analysis of vascular networks. Zudaire E, Gambardella L, Kurcz C, Vermeren S. PLoS One. 2011;6(11):e27385.

The GTPase-activating protein ARAP3 regulates chemotaxis and adhesion-dependent processes in neutrophils. Gambardella L, Anderson KE, Nussbaum C, Segonds-Pichon A, Margarido T, Norton L, Ludwig T, Sperandio M, Hawkins PT, Stephens L, Vermeren S. Blood. 2011 Jul 28;118(4):1087-98.

PI3K signaling through the dual GTPase-activating protein ARAP3 is essential for developmental angiogenesis. Gambardella L, Hemberger M, Hughes B, Zudaire E, Andrews S, Vermeren S. Sci Signal. 2010 Oct 26;3(145):ra76.

The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells. Janas ML, Hodson D, Stamataki Z, Hill S, Welch K, Gambardella L, Trotman LC, Pandolfi PP, Vigorito E, Turner M. J Immunol. 2008 Jan 15;180(2):739-46.

The paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype. Chan WY, Follows GA, Lacaud G, Pimanda JE, Landry JR, Kinston S, Knezevic K, Piltz S, Donaldson IJ, Gambardella L, Sablitzky F, Green AR, Kouskoff V, Göttgens B. Blood. 2007 Mar 1;109(5):1908-16.

The RNA binding protein Zfp36l1 is required for normal vascularisation and post-transcriptionally regulates VEGF expression. Bell SE, Sanchez MJ, Spasic-Boskovic O, Santalucia T, Gambardella L, Burton GJ, Murphy JJ, Norton JD, Clark AR, Turner M. Dev Dyn. 2006 Nov;235(11):3144-55.

Transgenic analysis of the stem cell leukemia +19 stem cell enhancer in adult and embryonic hematopoietic and endothelial cells. Silberstein L, Sánchez MJ, Socolovsky M, Liu Y, Hoffman G, Kinston S, Piltz S, Bowen M, Gambardella L, Green AR, Göttgens B. Stem Cells. 2005 Oct;23(9):1378-88.

Vav proteins regulate peripheral B-cell survival. Vigorito E, Gambardella L, Colucci F, McAdam S, Turner M. Blood. 2005 Oct 1;106(7):2391-8.

The multifaceted adult epidermal stem cell. Gambardella L, Barrandon Y. Curr Opin Cell Biol. 2003 Dec;15(6):771-7.

Selective rescue of early haematopoietic progenitors in Scl(-/-) mice by expressing Scl under the control of a stem cell enhancer. Sánchez MJ, Bockamp EO, Miller J, Gambardella L, Green AR. Development. 2001 Dec;128(23):4815-27.

The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle. Ellis T, Gambardella L, Horcher M, Tschanz S, Capol J, Bertram P, Jochum W, Barrandon Y, Busslinger M. Genes Dev. 2001 Sep 1;15(17):2307-19.

Pattern of expression of the transcription factor Krox-20 in mouse hair follicle. Gambardella L, Schneider-Maunoury S, Voiculescu O, Charnay P, Barrandon Y. Mech Dev. 2000 Sep;96(2):215-8.

Regular articles: conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration. Wang LC, Liu ZY, Gambardella L, Delacour A, Shapiro R, Yang J, Sizing I, Rayhorn P, Garber EA, Benjamin CD, Williams KP, Taylor FR, Barrandon Y, Ling L, Burkly LC. J Invest Dermatol. 2000 May;114(5):901-8.

Research Associate
Dr Laure  Gambardella

Affiliations

Collaborator profiles: 
Classifications: 
Person keywords: 
development
stem cells
regenerative medicine
cardiovascular biology