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  RESEARCH ACTIVITY > Extracellular Matrix (ECM) Pathobiology, Padova  
Extracellular Matrix (ECM) Pathobiology, Padova
Research Group

University of Padova
Department of Biomedical Sciences
Via U. Bassi, 58/b - 35121 Padova

Background and specific aims

The research activity carried out by Dr. M. Onisto began in 1987 at the  Inst. of Histology and Gen. Embryology of University of Padova , following the research topics:
a) the evaluation of soluble elastinic peptides in biological fluids in a project coordinated by Profs. L. Gotte and M. Spina;
b) the study of enzymatic processes involved in the degradation of some components of the extracellular matrix (ECM) in collaboration with Prof. S. Garbisa.
In particular, until 1996 the main research project involved the study of matrix metalloproteinases (MMP-2 or Gelatinase A), specific for type IV collagen of basement membranes, and its relative tissue inhibitor TIMP-2 ,whose cDNA he cloned at National Cancer Inst. of Bethesda (JBC 1990, Int.J. Cancer 1995, EMBO J. 1997)

Since 1997, he coordinates a research group continuing to study ECM remodeling and starting, at the same time, the study of genes and proteins involved in spermatogenesis. In particular he has cloned and characterized a new human protein associated with spermatogenesis initially named PD1 and then renamed SPATA2 (spermatogenesis-associated protein 2) in agreement with the Gene Nomenclature Committee and with the NCBI (National Center for Biotechnology Information) (Exp.Cell Res.1999)

Research projects
He currently deals with the study of heparanase (HPSE),  the unique and specific endoglycosidase capable of cleaving heparan sulfate (HS) chains. HS cleavage results in remodelling of ECM as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion (BMC Cancer 2009, Curr.Cancer Drug Target 2014, BBA-MCR 2014).
Figure 1 Heparanase: processing, localization, enzymatic and non-enzymatic activities. HPSE is synthesized in the endoplasmic reticulum as a latent precursor (pro-HPSE). After being moved to the Golgi apparatus, pro-HPSE is secreted outside the cell (1). HPSE uptake (mediated by syndecans, mannose-6-phosphate-receptor and low density lipoprotein receptor [LDLR]-related protein) (2) and its delivery to lysosome permits the proteolytic processing (by cathepsin L) and activation of the precursor into the dimeric active enzyme (3). The interaction of latent HPSE with HPSE binding proteins activates different intracellular signalling pathways implicated in angiogenesis, cell adhesion and migration (4). Upon different stimuli, HPSE secretion or translocation into the nucleus may occur. The degradation of extracellular HSPGs encourages cell migration thus enhancing tumor cell invasiveness and metastasis (5). Angiogenesis, EMT and inflammatory response is indirectly regulated by HPSE through HS-linked

Recent pubblications
Recent data concerning heparanase: focus on fibrosis, inflammation and cancer. - Secchi MF, Masola V, Zaza G, Lupo A, Gambaro G, Onisto M. - Biomol Concepts. Dec;6(5-6):415-21. doi: 10.1515/bmc-2015-0021 ( 2015 )
Heparanase as a target in cancer therapy - Masola V., Secchi M.F., Gambaro G., Onisto M. - Current Cancer Drug Target 14(3), 286-293 ( 2014 )
Heparanse is a key player in the renal fibrosis by regulating TGF-b expression and activity - Masola V., Zaza G., Secchi M.F., Gambaro G., Lupo A., Onisto M - BBA-Molecular Cell Research 1843(9):2122-28 ( 2014 )

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