Group Leader/s

 

intro

The global objective of the 3D laboratory (Development, Differentiation and Degeneration), has been to understand how the processes of cell proliferation, differentiation and cell death are regulated under physiological conditions, and to apply the acquired experience and knowledge to solve medical or technological challenges.

To the first aim, we have employed vertebrate models (chick, mouse), a lower eukaryote (Dictyostelium) and stem cells. We have studied the molecular and cellular mechanisms that drive nervous system development paying special attention to the process of programmed cell death. Programmed cell death is a physiological process of development that is also altered in different diseases. We have characterized its incidence and regulation in the development of the nervous system, especially in the retina. Double DNA strand breaks are generated and repaired, and this process impacts on the death of newly generated neurons. In turn, proinsulin (the molecular precursor of insulin) is a potent antiapoptotic factor during development, capable of activating several cell survival pathways.

The results generated in this line of basic research prompted us to extend our research to the study of programmed cell death in the context of neurodegenerative diseases. The retina, as part of the Central Nervous System, shares many physio-pathological traits with the brain. Retinitis Pigmentosa is a hereditary retinal neurodegenerative condition that leads to blindness. Currently there is not an effective treatment for this devastating disease. We began to explore the therapeutic potential of proinsulin. The promising results obtained with proinsulin in different rodent models of Retinitis Pigmentosa led us to found ProRetina Therapeutics in 2007, a spin-off of the CIB-CSIC whose mission was the development of therapies for retinal dystrophies. The results of our research have been included in a patent (licensed to ProRetina Therapeutics) and in an orphan drug dossier approved by the EMA and the FDA (the European and US agencies for drug regulation, respectively). Proinsulin has also showed neuroprotective efficacy in a model of age-cognitive loss underlying that therapeutic strategies towards retinal dystrophies should be consider for brain degenerative diseases and vice versa. 

We have expanded our studies to new families of neuroprotective molecules such as neurotrophins and the GSK-3 pathway with promising results. We are currently characterizing the role of inflammation on the course of retinal neurodegeneration focusing on different players of the innate immune response, with the aim of identifying novel potential therapeutic targets and developing experimental treatments. 

More recently, we have approached a multidisciplinary, nanotechnological challenge: the development of nano- and micro-devices able to measure different cellular parameters, such as pressure, PH, temperature, in living cells or animals. This leading edge of technology would allow for a more precise and early disease diagnose and follow up of experimental treatments. We have already relevant achievements in the development of silicon miniaturization technology which has allowed for the fabrication of nanostructured microdevices that can be internalized by living cells. In close collaboration with physicists and chemists, we are employing these tools to analyze and interfere with cellular processes from an innovative multidisciplinary perspective.

 

Martínez-Fernández de la Cámara C, Hernández-Pinto AM, Olivares-González L, Cuevas-Martín C, Sánchez-Aragó M, Hervás D, Salom D, Cuezva JM, de la Rosa EJ, Millán JM, Rodrigo R  [2015]. Adalimumab reduces photoreceptor dell death in a mouse model of retinal degeneration. Sci Report (DOI:10.1038/srep11764)

 

Funding

PROJECTS

PID2019-109506RB-100. MICINN (2020-2022). Explorando el papel de la inmunidad innata en la retinosis pigmentaria como proceso esencial y potencial diana terapéutica. Co-PIs: Enrique J. de la Rosa y Catalina Hernández Sánchez.

CRSII5_189967. Swiss National Science Foundation (01/05/20-30/04/2024). Nanoelectromechanical Systems for Intracellular Measurements. IP: Teresa Suárez (Coordinado).

- R+D contract with A4cell  "Validación del funcionamiento de SPAChips en cultivos celulares". (2018-2021) IP: Teresa Suárez

TEC2017-85059-C3-3-R. MICINN (2018-2020) Validación biológica de micro y nanoherramientas avanzadas en suspensión para aplicaciones intra y extracelulares. IP: Teresa Suárez (Coordinado).

SAF 2016-75681-R.MINECO (2017-2019). Alteraciones moleculares y celulares tempranas en Retinosis Pigmentaria y su posible valor como dianas terapéuticas. Co-PIs: Enrique J. de la Rosa y Flora de Pablo

SAF2013-41059-R. MICINN. 1/1/2014-31/12/2016. Estrategias neuroprotectoras para la Retinosis Pigmentaria basadas en la modulación de la muerte celular y la inflamación. Co-PIs: Flora de Pablo y Enrique J. de la Rosa

INNPACTO IPT-2011-0798-010000. 1/9/2011-31/12/2014. Development of neuroprotector and baroprotector drugs for glaucoma treatment. PI: Enrique J. de la Rosa, ProRetina Therapeutics S.L. (coordinator)

BFU-BMC 2010-15868. MICINN. 1/1/2011-3/12/2013. Regulación y función del locus TH-INS en el desarrollo embrionario y la diferenciación celular. PI: Flora de Pablo.

SAF2010-21879-C02-01. MICINN. 1/1/2011-31/12/2013. Physiological cell death and cellular fitness in development and differentiation and their imbalance in neural degeneration. PI: Enrique J. de la Rosa.

 TRACE PET2008-0065. March 2009-March 2011. Implicación del estrés oxidativo y del estrés de retículo en degeneraciones retinianas y su posible atenuación por proinsulina y otros factores neuroprotectores. PI: Enrique J. de la Rosa.

BFU2007-61055. MICINN. December 2007-december 2011. Transcritos quimera y otras formas atípicas de regulación génica y sus implicaciones en el desarrollo temprano. PI: Flora de Pablo and Catalina Hernández Sánchez

 Ministerio de Ciencia e Innovación (Subprograma Explora). 2010- 2011. ¿Es posible fabricar un nanosensor mecánico menor que una célula para medir la presión intracelular?. PI: Teresa Suarez (CIB group), Jose Antonio Plaza (coordinator) 

CONTRACTS

Contract with ProRetina Therapeutics S.L. “ Identification and characterization of the mechanism of action of proinsulin in Retinitis Pigmentosa”. December 2013-August 2014.

 

More info

Patents and Spin-off:

Members of the lab have promoted a technology based company, PRORETINA THERAPEUTICS, S.L. ( Madrid July 2007, Viveros Innovación CEIN 2009), as spin-off fromCIB, in collaboration with the Universities of Barcelona and Alcalá de Henares.  Director General: Stuart Medina; principal scientific partners: Enrique J. de la Rosa, Flora de Pablo, Fátima Bosch, Pedro de la Villa, Teresa Suárez, Patricia Boya, Catalina Hernández-Sánchez. Public-Private funds raised 2,5 million Euros. www.proretina.com.

 

Outreach activities:

 

López-Sancho P, Álvarez-Marrón F, de Pablo F, Masegosa Gallego J, Mayoral Gastón MC, Molina Hernández E, Pérez Sedeño E, Puertas Maroto F, Sandalio González LM. La Comisión de Mujeres y Ciencia del CSIC: diez años promoviendo la igualdad de oportunidades y la excelencia en el organismo. ARBOR 189(759):a012, 2013. (doi:http://dx.doi.org/103989/arbor.2013.759n1011).

De Pablo F, Suárez T. Inspiradoras excepcionales, además de investigadoras. SEBBM 173:33-34, 2012.

Pérez-Sedeño E, Álvarez-Marrón J, de Pablo F, López-Sancho P. Las mujeres en la ciencia y la tecnología: perspectiva internacional y situación en España. Themis 11:25-36, 2012.

De Pablo F. La saga Curie y las otras investigadoras. CIC Network. Abril 2011.

De Pablo F, de la Rosa EJ. El CIB, una mirada diferente: Investigación Básica y Transferencia de Tecnología. En: “Los cincuenta años del Centro de Investigaciones Biológicas: su impacto en el desarrollo de las ciencias biológicas en España”. Ed. Fundación Ramón Areces, Madrid, 2010.

De Pablo F. Retos y Perspectivas en Terapias basadas en Células. EIDON, 33. Ed. Fundación Ciencias de la Salud. Madrid, 2010.

Hoejgaard L et al. Human stem cell research and regenerative medicine- an European perspective on scientific, ethical and legal issues. Science Policy Briefing. European Science Foundation. May 2010.