Marco Sardiello




Assistant Professor, Baylor College of Medicine

B.S., University of Bari, Italy, 1999
Ph.D., University of Bari, Italy, 2003
Postdoc, Telethon Institute of Genetics and Medicine, 2004-09

Lysosomal enhancement as a therapeutic strategy for treating neuronal ceroid lipofuscinoses

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 finally results in diseases collectively known as lysosomal storage disorders (LSDs).

The primary focus of my laboratory is to develop innovative therapies for LSDs. The project sprang from our discovery of a gene network regulating lysosomal biogenesis and function. We found that the transcription factor EB (TFEB) is a master gene able to modulate 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 glycosaminoglycans and mutant huntingtin, which are pathologically accumulated in mucopolysaccharidoses and Huntington’s disease, respectively. Thus, TFEB is a potential therapeutic target to enhance cellular clearance in lysosomal storage disorders and neurodegenerative diseases. We are currently focusing on the role of the Batten gene, CLN3, in juvenile neuronal ceroid lipofuscinosis. The final aim of the project is to modulate TFEB activity in models of Batten disease as a therapeutic tool to enhance the clearance of toxic stored molecules.

My laboratory is also engaged in the study of other organellar gene networks. We discovered a mitochondrial gene network regulating 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 we named NRGBP. Drosophila mutants for this gene display severe impairment of energy metabolism and are larval lethal. Surprisingly, this gene network is analogous but non homologous to the mammalian mitochondrial network, being based on different molecules and regulatory signals.

Additional organellar gene networks in mammals and Drosophila are currently under study. The final aim is the dissection of the regulatory circuitry controlling the basal metabolism of the cell.

Selected Publications

Sardiello M, Licciulli F, Catalano D, Attimonelli M, Caggese C (2003) MitoDrome: a database of Drosophila melanogaster nuclear genes encoding proteins targeted to the mitochondrion. Nucleic Acids Research 31:322-324.

Sardiello M, Tripoli G, Oliva M, Santolamazza F, Moschetti R, Barsanti P, Lanave C, Caizzi R, Caggese C (2003) A comparative study of the porin genes encoding VDAC, a voltage-dependent anion channel protein, in Anopheles gambiae and Drosophila melanogaster. Gene 31:111-115.

Sardiello M, Tripoli G, Romito A, Minervini C, Viggiano L, Caggese C, Pesole G (2005) Energy biogenesis: one key for coordinating two genomes. Trends in Genetics 21:12-16.

Sardiello M, Annunziata I, Roma G, Ballabio A (2005) Sulfatases and sulfatase modifying factors: an exclusive and promiscuous relationship. Human Molecular Genetics 14:3203-3217.

Roma G, Sardiello M, Cobellis G, Cruz P, Lago G, Sanges R, Stupka E (2008) The UniTrap resource: tools for the biologist enabling optimized use of gene trap clones. Nucleic Acids Research 36(Database issue):D741-746.

Sardiello M, Cairo S, Fontanella B, Ballabio A, Meroni G (2008) Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties. BMC Evolutionary Biology 8:225.

Gennarino VA, Sardiello M, Avellino R, Meola N, Maselli V, Anand S, Cutillo L, Ballabio A, Banfi S (2009) MicroRNA target prediction by expression analysis of host genes. Genome Research 19:481-490.

Sardiello M, Ballabio A (2009) Lysosomal enhancement: a CLEAR answer to cellular degradative needs. Cell Cycle 8:4021-4022.

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 (2009) A gene network regulating lysosomal biogenesis and function. Science 325:473-477.

Palmieri M, Impey S, Kang H, di Ronza A, Pelz C, Sardiello M, Ballabio A (2011) Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Human Molecular Genetics 20:3852-3866.

Contact Information

Marco Sardiello, Ph.D.

Department of Molecular and Human Genetics
Baylor College of Medicine
1250 Moursund St. – NRI, Suite N1325
Houston, Texas 77030, U.S.A.

Tel: (832) 824-8871
Fax: (832) 825-1251

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