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Gennaro Napolitano

Assistant Investigator, TIGEM

Assistant Professor, Medical Genetics Unit, Department of Medical and Translational Science, Federico II University of Naples, Italy

Nutrient signaling and metabolic diseases

The main focus of our lab is understanding how the aberrant activation of metabolic signaling pathways underlies the pathogenesis of human genetic diseases. We are particularly interested in the study of the lysosome, a key organelle with nutrient sensing and signaling functions.

Mutations of genes important for the activity of the lysosome lead to a class of diseases, defined as lysosomal storage disorders (LSDs), which are characterized by alterations in metabolite availability and signaling.

On the other hand, deregulation of lysosomal activity and metabolic signaling is often observed in cancer cells, serving as an adaptation mechanism that allows cell survival and growth in the crowded tumor microenvironment.

We employ cell biology, proteomic, metabolomic and gene editing approaches to understand how cells sense and signal fluctuations in nutrient availability and how deregulation of these processes is involved in disease pathogenesis.

Our ultimate goal is to leverage these findings for the discovery of novel therapeutic targets in inherited metabolic diseases and cancer.

Napolitano G*, Di Malta C*, Esposito A, de Araujo EMG, Pece S, Bertalot S, Matarese M, Benedetti V, Zampelli A, Stasyk T, Siciliano D, Venuta A, Cesana M, Vilardo C, Nusco E, Monfregola J, Calcagni' A, Di Fiore PP, Huber LA and Ballabio A. A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome. Nature, 2020 Sep;585(7826):597-602.

Napolitano G, Esposito A, Choi H, Matarese M, Benedetti V, Di Malta C, Monfregola C, Medina DL, Lippincott-Schwartz J and Ballabio A. mTOR-dependent phosphorylation controls TFEB nuclear export. Nature communications. 2018 Aug 17;9(1):3312.

Napolitano G, Ballabio A. TFEB at a glance. J Cell Sci. 2016 Jul 1;129(13):2475-81. doi: 10.1242/jcs.146365. Epub 2016 Jun 1. Review.

Napolitano G, Johnson JL, Rocca CJ, Monfregola J, Cherqui S and Catz SD Impairment of chaperone-mediated autophagy leads to selective lysosomal degradation defects in the lysosomal storage disease cystinosis. EMBO Mol Med. 2015 Jan 12;7(2):158-74.

Johnson JL*, Napolitano G*, Monfregola J, Rocca CJ, Cherqui S and Catz SD. Upregulation of the Rab27a-dependent trafficking and secretory mechanisms improves lysosomal transport, alleviates endoplasmic reticulum stress, and reduces lysosome overload in cystinosis. Mol Cell Biol. 2013 Aug;33(15):2950-62.

Gennaro Napolitano PHD

Cell Biology and Disease Mechanisms

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