Alessandra d'Azzo, Ph.D.

Alessandra d'Azzo, Ph.D.

Genetics / Tumor Cell Biology
St. Jude Children's Research Hospital
Affiliated Professor
Department of Anatomy and Neurobiology

St. Jude Children's Research Hospital
Department of Genetics
Memphis, TN 38105
Email: Alessandra d'Azzo


  • Ph.D. Institution: University of Milano, Milan Italy; Erasmus University, Rotterdam, The Netherlands


Research Interests

The primary scope of this research program is to elucidate the fundamental role of the lysosomal system in normal cellular metabolism and in pathological conditions associated with lysosomal storage disorders (LSD).

Using a combination of molecular, genetic, and biochemical approaches, they have identified a multiprotein complex of three lysosomal hydrolases: protective protein/cathepsin A (PPCA), -galactosidase (-Gal), and neuraminidase (Neur). In the complex, PPCA (a serine carboxypeptidase) directly associates with the two glycosidases, a configuration needed for their intracellular routing, lysosomal activity, and stability. Three genetically distinct, human neurodegenerative LSD are caused by either single or combined deficiency of these enzymes: galactosialidosis, GM1-gangliosidosis, and sialidosis. To date, there is no effective therapy for these diseases. Using both in vitro systems and laboratory animals, they investigate the cell-specific expression and regulation of these enzymes, their intracellular trafficking, mode/site of association and activation, and their interaction with the substrates they cleave. They are also developing new therapeutic strategies in animal models for the future treatment of patients with these LSD. Greater knowledge of the function of these and other lysosomal proteins in the normal lysosome, as well as a better understanding of the structural and biochemical basis of the diseases, will aid in the design of new drugs and therapies.

The experimental approaches include: generation and characterization of knockout and transgenic mice; correction of affected mice by transplantation with transgenic over expressing or retrovirally transduced bone marrow; expression and regulation of normal and mutant enzymes in prokaryotic/eukaryotic cell systems; and crystal structure determination of over expressed proteins.

Representative Publications

  • Akgoc Z, Sena-Esteves M, Martin DR, Han X, d'Azzo A, Seyfried TN. Bis(monoacylglycero)phosphate: A secondary storage lipid in the gangliosidoses. J Lipid Res. 2015 Mar 20. pii: jlr.M057851. [Epub ahead of print] PubMed PMID: 25795792.
  • Heinecke KA, Luoma A, d'Azzo A, Kirschner DA, Seyfried TN. Myelin abnormalities in the optic and sciatic nerves in mice with GM1-gangliosidosis. ASN Neuro. 2015 Feb 18;7(1). pii: 1759091415568913. doi: 10.1177/1759091415568913. Print 2015 Jan-Feb. PubMed PMID: 25694553.
  • Annunziata I, Patterson A, d'Azzo A. Isolation of mitochondria-associated ER membranes (MAMs) and glycosphingolipid-enriched microdomains (GEMs) from brain tissues and neuronal cells. Methods Mol Biol. 2015;1264:25-33. doi: 10.1007/978-1-4939-2257-4_3. PubMed PMID: 25631000.
  • Katorcha E, Makarava N, Savtchenko R, D'Azzo A, Baskakov IV. Sialylation of prion protein controls the rate of prion amplification, the cross-species barrier, the ratio of PrPSc glycoform and prion infectivity. PLoS Pathog. 2014 Sep 11;10(9):e1004366. doi: 10.1371/journal.ppat.1004366. eCollection 2014 Sep. PubMed PMID: 25211026; PubMed Central PMCID: PMC4161476.
  • Chen GY, Brown NK, Wu W, Khedri Z, Yu H, Chen X, van de Vlekkert D, D'Azzo A, Zheng P, Liu Y. Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1. Elife. 2014 Sep 3;3:e04066. doi: 10.7554/eLife.04066. PubMed PMID: 25187624; PubMed Central PMCID: PMC4168287.
  • Bonardi D, Ravasio V, Borsani G, d'Azzo A, Bresciani R, Monti E, Giacopuzzi E. In silico identification of new putative pathogenic variants in the NEU1 sialidase gene affecting enzyme function and subcellular localization. PLoS One. 2014 Aug 25;9(8):e104229. doi: 10.1371/journal.pone.0104229. eCollection 2014. PubMed PMID: 25153125; PubMed Central PMCID: PMC4143216.

View more references (pubmed link)