Alessandra d'Azzo, Ph.D.

Alessandra d'Azzo, Ph.D.

Member
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



Education

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

Links

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

  • Platt FM, d'Azzo A, Davidson BL, Neufeld EF, Tifft CJ. Author Correction: Lysosomal storage diseases. Nat Rev Dis Primers. 2018 Oct 18;4(1):36. doi: 10.1038/s41572-018-0037-0. PubMed PMID: 30337566.
  • Platt FM, d'Azzo A, Davidson BL, Neufeld EF, Tifft CJ. Lysosomal storage diseases. Nat Rev Dis Primers. 2018 Oct 1;4(1):27. doi: 10.1038/s41572-018-0025-4. Review. Erratum in: Nat Rev Dis Primers. 2018 Oct 18;4(1):36. PubMed PMID: 30275469.
  • Romancino DP, Buffa V, Caruso S, Ferrara I, Raccosta S, Notaro A, Campos Y, Noto R, Martorana V, Cupane A, Giallongo A, d'Azzo A, Manno M, Bongiovanni A. Palmitoylation is a post-translational modification of Alix regulating the membrane organization of exosome-like small extracellular vesicles. Biochim Biophys Acta Gen Subj. 2018 Dec;1862(12):2879-2887. doi: 10.1016/j.bbagen.2018.09.004. Epub 2018 Sep 7. PubMed PMID: 30251702.
  • Annunziata I, Sano R, d'Azzo A. Mitochondria-associated ER membranes (MAMs) and lysosomal storage diseases. Cell Death Dis. 2018 Feb 28;9(3):328. doi: 10.1038/s41419-017-0025-4. Review. PubMed PMID: 29491402; PubMed Central PMCID: PMC5832421.
  • Annunziata I, d'Azzo A. Galactosialidosis: historic aspects and overview of investigated and emerging treatment options. Expert Opin Orphan Drugs. 2017;5(2):131-141. doi: 10.1080/21678707.2016.1266933. Epub 2016 Dec 14. PubMed PMID: 28603679; PubMed Central PMCID: PMC5461780.
  • Regier DS, Proia RL, D'Azzo A, Tifft CJ. The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy. Pediatr Endocrinol Rev. 2016 Jun;13 Suppl 1:663-73. Review. PubMed PMID: 27491214.

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