The del Monte-Nieto group is interested in the study of the molecular mechanisms and developmental processes orchestrating normal heart development in embryos by integrating all the cellular and non-cellular components involved.

The lab aims to apply multidisciplinary approaches including mathematical modeling and bioengineering to developmental biology studies in order to generate in silico and in vitro models to  confirm our biological results and formulate new hypothesis. 

The knowledge generated from these basic developmental biology models will allow us to generate new insights to better understand the processes responsible for the onset of congenital cardiac disease and to identify potential targets to design efficient genetic screening for patients and therapies to ameliorate disease sequelae including improving the regeneration capacity of the heart after infarction. 

Furthermore, these bioengineered in vitro models will help us to develop improved and more efficient engineered tissues for transplantation and organ-on-a-chip devises for personalized drug screening.  

Funding acknowledgements

Dr Gonzalo del Monte-Nieto received his PhD in 2011 from the Autonomous University of Madrid (Spain), training in molecular and developmental biology supervised by Prof José Luis de la Pompa (CNIC, Madrid, Spain) and on 3D image analysis by Prof Antoon Moorman (AMC, Amsterdam, the Netherlands).

During this time, he developed a protocol for monitoring the Notch1 activity during development that not only helped to describe for the first time the cells and tissues where the Notch pathway is active in the developing embryo and adult tissues, but also to decode complex developmental processes such as cardiac ventricular trabeculation, valvulogenesis and somitogenesis.

Furthermore, his PhD work determined for the first time the role of the Notch pathway during epicardium and coronary artery formation.

In 2011, he joined Prof Richard Harvey laboratory at Victor Chang Cardiac Research Institute (Sydney). His research focus lays in the study of the molecular mechanisms and developmental processes orchestrating heart development and the translation of this knowledge into congenital heart disease and cardiac regeneration.

On this regard, his recent research has described a new revolutionary model for cardiac chamber development with special focus in trabeculation by integrating the cellular and extracellular components of the heart with important implications for better understanding congenital and adult heart disease.

Authors
Title
Published In

del Monte-Nieto G*, Ramialison M, Adam AAS, Wu B, Aharonov A, D’Uva G, Bourke LM, Pitulescu ME, Chen H, de la Pompa JL, Shou W, Adams RH, Harten SK, Tzahor E, Zhou B and Harvey RP*.*Co-corresponding author.

Control of cardiac jelly dynamics by NOTCH1 and NRG1 defines the building plan for trabeculation.

Nature. 2018 May 17;557(7705):439-445. doi: 10.1038/s41586-018-0110-6. Epub 2018 May 9. PMID:29743679. 

Wang Y, Wu B, Lu P, Zhang D, Wu B, Varshney S, del Monte-Nieto G, Zhuang Z, Charafeddine R, Kramer AH, Sibinga NE, Frangogiannis NG, Kitsis RN, Adams RH, Alitalo K, Sharp DJ, Harvey RP, Stanley P, Zhou B.

Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1.

Nature Communications. 2017 Sep 18;8(1):578. doi: 10.1038/s41467-017-00654-w. PMID: 28924218.

Vennin C, Chin VT, Warren SC, Lucas MC, Herrmann D, Magenau A, Melenec P, Walters SN, del Monte-Nieto G, Conway JR, Nobis M, Allam AH, McCloy RA, Currey N, Pinese M, Boulghourjian A, Zaratzian A, Adam AA, Heu C, Nagrial AM, Chou A, Steinmann A, Drury A, Froio D, Giry-Laterriere M, Harris NL, Phan T, Jain R, Weninger W, McGhee EJ, Whan R, Johns AL, Samra JS, Chantrill L, Gill AJ, Kohonen-Corish M, Harvey RP, Biankin AV, Australian Pancreatic Cancer Genome Initiative (APGI), Evans TR, Anderson KI, Grey ST, Ormandy CJ, Gallego-Ortega D, Wang Y, Samuel MS, Sansom OJ, Burgess A, Cox TR, Morton JP, Pajic M, Timpson P.

Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy and the onset of the metastatic niche.

Science Translational Medicine. 2017 Apr 5;9(384). pii: eaai8504. doi: 10.1126/scitranslmed.aai8504. PMID: 28381539.

Bourke LM*, del Monte-Nieto G*, Outhwaite JE, Bharti V, Pollock PM, Simmons DG, Adam A, Hur SS, Maghzal GJ, Whitelaw E, Stocker R, Suter CM, Harvey RP, Harten SK. *Co-first Author

Loss of Rearranged L-Myc Fusion (RLF) results in defects in heart development in the mouse.

Differentiation. 2016 Dec 5;94:8-20. doi: 10.1016/j.diff.2016.11.004. PMID: 27930960.

MacGrogan D, D´Amato G, Travisano S, Martinez-Poveda B, Luxán G, del Monte-Nieto G, Sbroggio M, Gomez del Arco P, Gómez MJ, Zhou B, Redondo JM, de la Pompa JL.

Sequential ligand-dependent Notch signalling activation regulates valve primordium formation and morphogenesis.

Circulation Research. 2016 May 13;118(10):1480-97. doi: 10.1161/CIRCRESAHA.115.308077. Epub 2016 Apr. PMID: 27056911. 

D'Amato G, Luxán G, del Monte-Nieto G, Martínez-Poveda B, Torroja C, Walter W, Bochter MS, Benedito R, Cole S, Martinez F, Hadjantonakis AK, Uemura A, Jiménez-Borreguero LJ and de la Pompa JL.

Sequential Notch activation regulates ventricular chamber development.

Nature Cell Biology. 2016 Jan; 18(1):7-20. doi:10.1038 /ncb3280. Epub 2015 Dec 7. PMID: 26641715.

del Monte G, Casanova JC, Guadix JA, MacGrogan D, Burch JB, Perez-Pomares JM, de la Pompa JL.

Differential Notch signalling in the epicardium is required for cardiac inflow development and coronary vessel morphogenesis.

Circulation Research. 2011 Apr 1;108(7):824-36. doi: 10.1161/CIRCRESAHA.110.229062. Epub 2011 Feb 10. PMID: 21311046. 

Luna-Zurita L, Prados B, Grego-Bessa J, Luxan G, del Monte G, Benguria A, Adams RH, Perez-Pomares JM, de la Pompa JL.

Journal of Clinical Investigation. 2010 Oct;120(10):3493-507. doi: 10.1172/JCI42666. Epub 2010 Sep 20. PMID: 20890042.

 Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation.

del Monte G, Grego-Bessa J, Gonzalez-Rajal A, Bolos V, De La Pompa JL.

Monitoring Notch1 activity in development: evidence for a feedback regulatory loop.

Developmental Dynamics. 2007 Sep;236(9):2594-614. PMID: 17685488. 

Grego-Bessa J, Luna-Zurita L, del Monte G, Bolos V, Melgar P, Arandilla A, Garratt AN, Zang H, Mukouyama YS, Chen H, Shou W, Ballestar E, Esteller M, Rojas A, Perez-Pomares JM, de la Pompa JL.

Notch signaling is essential for ventricular chamber development.

 Developmental Cell. 2007 Mar;12(3):415-29. PMID:17336907.