Alessandra d

    Alessandra d'Azzo, PhD

    Member, St. Jude Faculty
    Jewelers For Children Endowed Chair in Genetics and Gene Therapy



    Contact Information

    Alessandra d'Azzo, PhD
    MS 331, Room D3055C
    St. Jude Children's Research Hospital
    262 Danny Thomas Place
    Memphis, TN 38105-3678
    Phone: (901) 595-2698
    FAX: (901) 526-2907


    MS - University of Pavia, Italy (1979)
    PhD - University of Milano, Italy (1973)
    PhD - Erasmus University, Rotterdam, The Netherlands (1982)

    Research Interests

    Alessandra d’Azzo, PhD, has a long-standing interest in the processes that control the intracellular breakdown of proteins in both normal and disease conditions. Her research focuses on the interplay between compartmentalized degradation occurring in lysosomes and cytosolic degradation mediated by the proteasome. Her accomplishments include the discovery of the primary defect in the lysosomal storage disease, galactosialidosis, the development and characterization of specific animal models for several lysosomal disorders, and more recently the discovery of a new muscle-specific ubiquitin ligase involved in myogenesis and muscle homeostasis.

    The primary scope of Dr. d’Azzo’s research is to unravel mechanisms involved in the pathogenesis of lysosomal storage disorders, particularly those affecting glycoprotein and glycosphigolipid metabolism, and to elucidate the function of a muscle-specific ubiquitin ligase in development and maintenance of skeletal and cardiac muscle. The generation of faithful mouse models for several lysosomal storage diseases has enabled her to study in depth the impact of enzyme deficiency and accumulation of specific metabolites on cell and tissue homeostasis. She successfully used these laboratory animals to implement preclinical therapeutic modalities, including enzyme replacement, bone marrow transplantation, and in vivo and ex vivo gene therapy.



    Selected Publications

    Romancino DP, Anello L, Morici G. d’Azzo A, Bongiovanni A, Di Bernardo M. Identification and characterization of PIAIix, the Alix homologue from the Mediterranean sea urchin Paracentrotus lividus. Dev Growth Differ Jan 10, 2013. doi: 10.111/dgd. 12023. [Epub ahead of print].

    Lehman A, Mattman A, Sin , Pare P, Zong Z, d’Azzo A, Campos Y, Sirrs S, Hinek A. Emphysema in an adult with galactosialidosis linked to a defect in primary elastic fiber assembly. Mol Genet Metab 106(1):99-103, 201, 2012.

    Bongiovanni A, Romancino DP, Campos Y, Paterniti G, Qiu X, Moshiach S, Di Felice V, Vergani N, Ustek D, d’Azzo A. Alix is a substrate of the Ozz-E3 ligase, and modulates actin remodeling in skeletal muscle. J Biol Chem 287(15):12159-71, 2012.

    Hu H, Gomero E, Bonten E, Gray JT, Allay J, Wu Y, Wu J, Calabrese C, Nienhuis A, d'Azzo A. Preclinical dose-finding study with a liver-tropic, recombinant AAV-2/8 vector in the mouse model of galactosialidosis. Mol Ther 20(2):267-74, 2012.

    Caciotti A, Garman SC, Rivera-Colon Y, Procopio E, Catarzi S, Ferri L, Guido C, Martelli P, Parini R, Antuzzi D, Battini R, Siblio M, Simonati A, Fontana E, Salviati A, Akinci G, Cereda C, Dionisi-Vici C, Deodato F, d’Amico A, d’Azzo A, Bertini E, Filocamo M, Scarpa M, di Rocco M, Tifft CJ, Ciani F, Gasperini S, Pasquini E, Guerrini R, Donati MA, Morrone A. GM1 gagliosidosis and Morquio B disease: An update on genetic alterations and clinical findings. Biochim Biophys Acta Mol Basis Dis 1812(7):782-80, 2011.

    d’Azzo A, Bonten E. Molecular mechanisms of pathogenesis in a glycosphingolipid and a glycoprotein storage disease. Biochem Soc Trans 38 (6): 453-7, 2010.

    Baek RC, Broekman ML, Leroy SG, Tierney LA, Sandberg MA, d’Azzo A, Seyfried TN, Sena-Esteves M. AAV-mediated gene delivery in adult GM1-gangliosidosis mice corrects lysosomal storage in CNS and improves survival. PLoS One 5(10):1-16, 2010.

    Monti E, Bonten E, d’Azzo A, Bresciana R, Venerando B, Borsani G, Schauer R, Tettamanti G. Sialidases in vertebrates: a family of enzymes tailored for several cell functions. Adv Carbohydr Chem Biochem 64:403-79, 2010.

    Stamatos NM, Carubelli I, van e Vlekkert D, Bonten EJ, Papini N, Feng C, Venerado B, d’Azzo A, Cross AS, Wang LX, Gomatos PJ. LPS-induced cytokine production in human dendritic cells is regulared by sialidase activity. J Leukoc Biol 88(6):1227-39, 2010.

    Zanoteli E, de Vlekkert DV, Bonten EJ, Hu H, Mann L, Gomero EM, Harris AJ, Ghersi G, d’Azzo A. Muscle degeneration in neuraminidase 1 deficient mice results from infiltration of the muscle fibers by expanded connective tissue. Biochim Biophys Acta 1802(1-2):659-672, 2010.

    Campos Y, Qiu X, Zanoteli E, Moshiach S, Vergani N, Bongiovanni A, Harris AJ, d’Azzo A. Ozz E3 ubiquitin ligase targets sarcomeric embryonic myosin heavy chain during muscle development. PLoS One 5(3):e9066, 2010.

    Wu X, Steigelman KA, Bonten E, Hu H, He W, Ren T, Zuo J, d’Azzo A. Vacuolization and alterations of lysosomal membrane proteins in cochlear marginal cells contribute to hearing loss in neuraminidase 1-deficient mice. Biochim Biophys Acta 1802:259-268, 2010.

    *Sano R, *Annunziata I, Patterson A, Moshiach S, Gomero E, Opferman J, Forte M, d’Azzo A. GM1-ganglioside accumulation at the mitochondria-associated ER membranes links ER stress to Ca2 -dependent mitochondrial apoptosis. Mol Cell 36(3):500-511, 2009. *Equal Contributors

    Wu X, Steigelman KA, Bonten E, Hu H, He W, Ren T, Zuo J, d’Azzo A. Vacuolization and alterations of lysosomal membrane proteins in cochlear marginal cells contribute to hearing loss in neuraminidase 1-deficient mice. Biochim Biophys Acta1802(2):259-268, 2009.

    Bonten EJ, Campos Y, Zaitsev V, Nourse A, Waddell B, Lewis W, Taylor G. d’Azzo A. Heterodimerization of the sialidase NEU1 with the chaperone protective protein/cathepsin A prevents its premature oligomerizaion. J Biol Chem 284(41):28430-28441, 2009.

    Wang D, Zaitsev S, Taylor G, d’Azzo A, Bonten E. Protective Protein/Cathepsin A rescues N-glycosylation defects in neuraminidase-1. Biochim Biophys Acta 1790(4):275-282, 2009.

    Caciotti A, Di Rocco M, Filocamo M, Grossi S, Traverso F, d'Azzo A, Cavicchi C, Messeri A, Guerrini R, Zammarchi E, Donati MA, Morrone A. Type II sialidosis: review of the clinical spectrum and identification of a new splicing defect with chitotriosidase assessment in two patients. J Neurol 256(11):1911-1915, 2009.

    Starcher B, d’Azzo A, Keller PW, Rao GK, Nadarajah D, Hinek A. Neuraminidase-1 is required for the normal assembly of elastic fibers. Am J Physiol Lung Cell Mol Physiol 295:L637-47, 2008.

    *Yogalingam G, *Bonten EJ, van de Vlekkert D, Hu H, Connell SA, Moshiach S, d’Azzo A. Neuraminidase 1 is a Negative Regulator of Lysosomal Exocytosis. Dev Cell 15:74-86, 2008. *Equal Contributors

    Elliot-Smith, E, Speak AO, Lloyd-Evans E, Smith DA, van der Spoel AC, Jeyakumar M, Butters TD, Dwek RA, d’Azzo A, Platt FM. Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. Mol Genet Metab 94:204-211, 2008.

    Sano R, Tessitore A, Ingrassia A, d’Azzo A. Chemokine-induced recruitment of genetically modified hematopoietic cells into the CNS of GM1-gangliosidosis mice corrects neuronal pathology. Blood 106:2259-68, 2005.

    Wang D, Bonten EJ, Yogalingam F, Mann L, d’Azzo A. Short Term, High Dose Enzyme Replacement Therapy in Sialidosis Mice. Mol Genet Metab 85:181-189, 2005.

    Kasperzyk J, d’Azzo A, Platt F, Alroy J, Seyfried TN. Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice. J Lipid Res 46:744-51, 2005.

    Gururaj A, Sztriha L, Hertecant J, Johansen JG, Giorgiou T, Campos Y, Drousiotou A, d’Azzo A. Magnetic resonance imaging findings and novel mutations in GM1 gangliosidosis. J Child Neurol 20:57-60, 2005.

    d’Azzo A, Bongiovanni A, Nastasi T. E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation. Traffic 6:429-41, 2005.

    Complete list of publications

    Last update: February 2013