Head of High Content Screen Facility
Associate Professor of Biology, Department of Translational Medicine, University of Naples “Federico II”, Italy
Diego L. Medina obtained his PhD in Biochemistry and Molecular Biology in 2000, at the UAM/CSIC of Madrid, Spain. Since 2011, Prof Medina has held positions as Assistant Investigator and Head of the High Content Screening Facility at the Telethon Institute of Genetics and Medicine (TIGEM). Since April 2019, he has also held a position at the University of Naples “Federico II” as Associate Professor in Biology at the Medical Genetics Unit, Department of Medical and Translational Science. Prof. Medina’s research group focuses on the study of the fundamental biological role of lysosomal function in health and disease using state-of-the-art high content imaging (HCI), cell biology, and OMICs approaches. Information from basic research is then exploited for the development of new therapeutic strategies to treat rare genetic diseases. Medina has published 57 articles in peer-review international journals. His work is supported by many funding sources including the Horizon 2020 proposal (of which he is WP leader) and the Italian Telethon Foundation. He also receives support from a number of foundations which focus on specific diseases including the ML4 Foundation, CTF&CATS Foundation, Cure San Filippo Foundation, and MDBR grant program.
Lysosomal calcium signalling and autophagy
We contributed to the discovery that lysosomal biogenesis and autophagy are transcriptionally regulated by the transcription factor EB (TFEB). Upon nutrient starvation mTOR signalling is inhibited while TFEB and its network of target genes are activated. We discovered that lysosomal Ca2+ release through the non-selective cation channel TRPML1 plays a major role in lysosomal adaptation to starvation by activating the Ca2+-dependent phosphatase calcineurin, that de-phosphorylates and activates TFEB (Medina DL, et al, 2015). Focusing in TRPML1, we also found that its activation plays a major role in the initiation of autophagy by promoting autophagosome biogenesis through the AMPK/VPS34 pathway. Our laboratory is now focused on; 1) the study of TRPML1 activation upon nutrient deprivation; 2) the role of TRPML1 and lysosomal calcium signalling in autophagy, and 3) the identification of TRPML1 interactors involved on lysosomal function and signalling. To study these important aspects of lysosomal biology we are utilizing molecular and cellular biology, High Content Imaging, and OMIC approaches.
Repurposing approach to cure lysosomal storage disorders
We contributed to the discovery that TFEB over-expression can promote cellular clearance in different lysosomal storage disorders (LSDs) by inducing lysosomal exocytosis, a process that requires TRPML1-dependent Ca2+ release (Medina DL, et al, 2011). This seminal finding was subsequently independently confirmed by many other labs, suggesting that either TRPML1 or TFEB may represent novel therapeutic targets for the identification of compounds modulating its clearance activity. Over the last few years, we have developed cell-based high content imaging screening approaches to identify compounds able to induce the TFEB pathway in cellular models of LSDs. In particular, we have focused on the repurposing of FDA-approved drugs to tackle Batten Diseases, Mucopolysaccharidosis and Mucolipidosis type IV. The identification of FDA drugs correcting LSDs may significantly reduce the costs and time associated with clinical translation.
Diego Medina is the head of the High Content Screening Facility
. HCS is an analysis tool used to acquire, manage, and search multi-parametric information regarding the composite phenotype of cells.