3D Lab Development, Differentiation & Degeneration

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.