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Leopoldo Staiano

Assistant Investigator, TIGEM

Researcher, Institute of Genetic and Biomedical Research-IRGB-CNR, UOS of Milan

Intracellular trafficking in kidney development and pathophysiology.

Different inherited kidney diseases, such as Lowe Syndrome (caused by mutation in OCRL gene), Dent disease (CLCN5), Fabry disease (GLA) and Cystinosis (CTNS) are characterized by common clinical manifestations. Within the kidney, defective proximal tubule reabsorption of proteins, amino acids, vitamins and solutes is a common hallmark of such diseases, whose pathogenetic mechanisms are far from being completely unraveled/understood. The convergence towards similar clinical phenotypes among patients with mutations in these genes can rarely be associated to the involvement of the same cellular pathway. This highlights an important unsolved question such as how mutations in four different genes with diverse functions may affect the same kidney cell type, resulting in a very similar clinical outcome.
Since most of these disease-causative genes play key roles in different branches of intracellular membrane trafficking (endocytosis, lysosomal function, autophagy), we will investigate the contribution of these processes to kidney development and pathophysiology, combining Systems Biology, in vitro and in vivo approaches.
We will investigate the way membrane trafficking system is regulated during kidney development, by which mechanisms it regulates kidney morphogenesis and how and why the deregulation of different steps of membrane trafficking leads to similar cell-specific pathological alterations with the final possibility to identify common deregulated mechanisms that could represent points for therapeutic intervention. Furthermore, to deeply decipher the sub-tissutal specificity of pathological manifestation and to develop new pharmacological approaches for human genetic kidney diseases, we will take advantage of the gold standard technology of kidney organoids. These models will be used to analyze cell specific transcriptional and translational programs in physiological and pathological conditions, and will be exploited in drug and viral vector screening experiments, with the aim to pave the way towards new therapeutic approaches for genetic kidney diseases that are nowadays incurable.

Undergraduate Student:Angela Nacca
Guest Student: Josephine Zeiger 

Gambardella G*, Staiano L*, Moretti MN, De Cegli R, Fagnocchi L, Di Tullio G, Polletti S, Braccia C, Armirotti A, Zippo A, Ballabio A, De Matteis MA, di Bernardo D. GADD34 is a modulator of autophagy during starvation. Sci Adv 2020 Sep 25;6(39):eabb0205. doi: 10.1126/sciadv.abb0205. Print 2020 Sep.

De Leo MG*, Staiano L*, Vicinanza M, Luciani A, Carissimo A, Mutarelli M, Di Campli A, Polishchuk E, Di Tullio G, Morra V, Levtchenko E, Oltrabella F, Starborg T, Santoro M, Di Bernardo D, Devuyst O, Lowe M, Medina DL, Ballabio A, De Matteis MA. Autophagosome-lysosome fusion triggers a lysosomal response mediated by TLR9 and controlled by OCRL. Nat Cell Biol. 2016 Aug;18(8):839-850. doi: 10.1038/ncb3386. Epub 2016 Jul 11.

Festa BP, Berquez M, Gassama A, Amrein I, Ismail HM, Samardzija M, Staiano L, Luciani A, Grimm C, Nussbaum RL, De Matteis MA, Dorchies OM, Scapozza L, Wolfer DP, Devuyst O. OCRL deficiency impairs endolysosomal function in a humanized mouse model for Lowe syndrome and Dent disease. Hum Mol Genet. 2019 Jun 15;28(12):1931-1946. doi: 10.1093/hmg/ddy449.

De Matteis MA, Staiano L, Emma F, Devuyst O. The 5-phosphatase OCRL in Lowe syndrome and Dent disease 2. Nat Rev Nephrol. 2017 Aug;13(8):455-470. doi: 10.1038/nrneph.2017.83. Epub 2017 Jul 3.

Staiano L, De Leo MG, Persico M, De Matteis MA. Mendelian disorders of PI metabolizing enzymes. Biochim Biophys Acta. 2015 Jun;1851(6):867-81. doi: 10.1016/j.bbalip.2014.12.001. Epub 2014 Dec 12.

Leopoldo Staiano PHD

Cell Biology and Disease Mechanisms

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