- Associate Professor
- Molecular and Human Genetics
- Baylor College of Medicine
- Houston, TX, US
- BS from Universita Bari
- PhD from Universita Bari
- Post-Doctoral Fellowship at Telethon Institute Of Genetics And Medicine
- Regulatory networks of cell metabolism and neurological disorders
My laboratory uses genetics, cell biology and systems biology approaches to study how the cell regulates its metabolic programs and how dysfunctions in these programs lead to neurological disease. Our ultimate goal is to translate our knowledge of these regulatory networks into therapeutic approaches for neurodegenerative disorders.
Using systems biology approaches, we discovered and characterized a gene network regulating lysosomal biogenesis and function. Lysosomes are cellular organelles central to degradation and recycling processes. Defects in genes participating in lysosomal function lead to the accumulation of toxic substances into the cell, which ultimately results in diseases collectively known as lysosomal storage disorders (LSDs). We discovered that the transcription factor EB (TFEB) is a master regulator of the biogenesis and activity of lysosomes. Under aberrant lysosomal storage conditions, TFEB translocates from the cytoplasm to the nucleus, resulting in the activation of genes with lysosomal function. TFEB overexpression induces lysosomal biogenesis and increases the clearance of ceroid lipopigment, glycosaminoglycans and mutant huntingtin, which are pathologically accumulated in Batten disease, mucopolysaccharidoses and Huntington’s disease, respectively. We are now using genetic and chemical tools to modulate TFEB activity in mouse models of neurodegenerative diseases to enhance the clearance of stored molecules and determine the effects on disease symptoms.
My laboratory is also investigating other regulatory networks. We have discovered a mitochondrial gene network that regulates energy metabolism in Drosophila. Nuclear and mitochondrial genes involved in oxidative phosphorylation are connected in a common regulatory circuit, for which we have now identified a candidate master regulator. Drosophila mutants for this gene display severe impairment of energy metabolism and die at the larval stage. Surprisingly, this gene network is analogous, but non homologous, to the mammalian mitochondrial network, being based on different molecules and regulatory signals.
Additional metabolic gene networks regulated by transcription factors or microRNAs are currently under study. These studies aim at dissecting the regulatory circuitry that controls the basal metabolism of the cell.
- Pal R, Palmieri M, Loehr JA, Li S, Abo-Zahrah R, Monroe TO, Thakur PB, Sardiello M, Rodney GG. "Src-dependent impairment of autophagy by oxidative stress in a mouse model of Duchenne muscular dystrophy." Nat Commun. 2014 July 16;5:4425. Pubmed PMID: 25028121
- Mauri V, Lotfi P, Segatori L, Sardiello M. "A rapid and sensitive method for measuring N-acetylglucosaminidase activity in cultured cells." PLoS One. 2013;8(6):e68060. Pubmed PMID: 23840811
- Song W, Wang F, Savini M, Ake A, di Ronza A, Sardiello M, Segatori L. "TFEB regulates lysosomal proteostasis." Hum Mol Genet. 2013 May 15;22(10):1994-2009. Pubmed PMID: 23393155
- Gennarino VA, D'Angelo G, Dharmalingam G, Fernandez S, Russolillo G, Sanges R, Mutarelli M, Belcastro V, Ballabio A, Verde P, Sardiello M, Banfi S. "Identification of microRNA-regulated gene networks by expression analysis of target genes." Genome Res. 2012 June;22(6):1163-72. Pubmed PMID: 22345618
- Medina DL, Fraldi A, Bouche V, Annunziata F, Mansueto G, Spampanato C, Puri C, Pignata A, Martina JA, Sardiello M, Palmieri M, Polishchuk R, Puertollano R, Ballabio A. "Transcriptional activation of lysosomal exocytosis promotes cellular clearance." Dev Cell. 2011 September 13;21(3):421-30. Pubmed PMID: 21889421
- Palmieri M, Impey S, Kang H, di Ronza A, Pelz C, Sardiello M, Ballabio A. "Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways." Hum Mol Genet. 2011 October 1;20(19):3852-66. Pubmed PMID: 21752829
- Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, Sardiello M, Rubinsztein DC, Ballabio A. "TFEB links autophagy to lysosomal biogenesis." Science. 2011 June 17;332(6036):1429-33. Pubmed PMID: 21617040
- Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A. "A gene network regulating lysosomal biogenesis and function." Science. 2009 July 24;325(5939):473-7. Pubmed PMID: 19556463
- Gennarino VA, Sardiello M, Avellino R, Meola N, Maselli V, Anand S, Cutillo L, Ballabio A, Banfi S. "MicroRNA target prediction by expression analysis of host genes." Genome Res. 2009 March;19(3):481-90. Pubmed PMID: 19088304
- Sardiello M, Cairo S, Fontanella B, Ballabio A, Meroni G. "Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties." BMC Evol Biol. 2008;8:225. Pubmed PMID: 18673550
- Sardiello M, Annunziata I, Roma G, Ballabio A. "Sulfatases and sulfatase modifying factors: an exclusive and promiscuous relationship." Hum Mol Genet. 2005 November 1;14(21):3203-17. Pubmed PMID: 16174644