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Giovanni D'Angelo

Research Focus : Decoding the Language of Glycosphingolipids

Unlike nucleic acids and peptides, glycans are template-free biopolymers. Their ‘sequences’ are indeed not strictly genetically determined, but rather they depend on the configuration of dedicated cellular synthetic machineries. Nevertheless specific glycans have roles in nearly every biological process and are involved in many major human diseases. Thousands of different glycans decorate glycoproteins and glycolipids, the most relevant class of which is the glycosphingolipids (GSLs). These are amphipathic compounds that are characterised by complex glycan structures linked to a ceramide backbone. According to the LIPID MAPS Structure Database, more than 400 different glycanscan be assembled on ceramide in vertebrates, the theoretical information content of which is extremely high. Manipulation of GSL synthesis in animal models has led to the concept that although cells can survive in the absence of GSLs, vertebrates need GSLs to correctly complete their development, and for a number of GSLs, modulatory effects on specific plasma-membrane receptors have been demonstrated.  By changing the competence of receptors to respond to extrinsic signals, GSLs can diversify the possible outcomes of a given signalling pathway thus impacting on the establishment of cell identity in multicellular contexts. Therefore GSLs could represent a non-genetically encoded ‘biological language’, that cells use to establish and maintain their identities during developmental processes. The ‘syntax’ and ‘semantics’ of thislanguage are, however, unclear. Indeed, the understanding of the biological significance of such a vast repertoire of molecules remains bound to the elucidation of three unsolved key aspects: (i) How do individual cells determine their GSL make-up (the ‘GSL grammar’)? (ii) What are the cellular factors that interact with, and are regulated by, specific GSLs (the ‘GSL coding’)? (iii) What signalling pathways and regulatory gene networks are influenced by the cellular GSL composition (the GSL meaning)? Our Lab focuses on the study of these three key aspects by integrating biochemical, cell biology, and systems biology approaches. 

Curriculum

Since the very beginning of my scientific career I have been fascinated by Cell Biology and the Biosynthetic Pathway. Compared to other aspects of Biology I found this one of special interest for two main reasons. First, it deals with phenomena where cellular functions were mirrored by specific cellular structures; secondly, according to my naïve point of view at the time, it lacked the same cogent molecular descriptions that were provided for other aspects of Biology, thus leaving space for future discoveries. At the present, my scientific interests are at the crossroads between membrane trafficking, glycosphingolipid biology, and regulatory circuits. All of the projects in my laboratory deal with these concepts and are aimed at investigating the biosynthetic pathway in terms of an information-processing unit inside the cell.

Education

  • 2008 PhD   Open University, Milton Keynes – Consorzio “Mario Negri” Sud, Santa Maria Imbaro, Italy.
  • 2003 Master Degree in Medical Biotechnology, Medical School, University of Naples “Federico II”

Positions

  • 2011-present Researcher at Institute of Protein Biochemistry – National Research Council of Italy. Naples.
  • 2010-2011 PostDoc at Telethon Institute for Genetics and Medicine (TIGEM), Naples.
  • 2008-2009 PostDoc at Consorzio “Mario Negri” Sud, Santa Maria Imbaro
  • 2004-2008 PhD Student at Consorzio “Mario Negri” Sud, Santa Maria Imbaro
  • 1999-2003 Undergraduate Research trainee. Dept. of Biochemistry and Medical Biotechnology (DBBM), Medical School, University of  Naples “Federico II”, Naples.

Conference Organization

  •  2014 EMBO workshop on “Cellular imaging of lipids ”, Vico Equense, Italy, 2 – 6 June 2014.

Fellowships and Grants  

  • 2005-2008 FIRC  fellowship
  • 2008-2009 FIRC  fellowship
  • 2010-2013 My First  AIRC Grant (MFAG)
  • 2014-2017 Grant Ricerca Finalizzata GR (Ministry of Health)

Patents

  • 2014 FAPP2 inhibitors and uses thereof (filed)
  • 2013 The descent of language - A conversation between two jobless biologists; S&F_n. 10_2013; ISSN 2036-292

Non-Scientifi Publications

  • 2013 The descent of language - A conversation between two jobless biologists; S&F_n. 10_2013; ISSN 2036-2927

Selected Scientific Publications

  • Glycosphingolipids: synthesis and functions
    D’Angelo G, Capasso S, Sticco L, Russo D.
  • Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi.  
    D'Angelo G et al.
    Nature. 2013 Sep 5;501(7465):116-20
  • Identification of microRNA-regulated gene networks by expression analysis of target genes. Gennarino VA,
    D'Angelo G, et al.
    Genome Res. 2012 Jun;22(6):1163-72
  • GRASP65 and GRASP55 sequentially promote the transport of C-terminal valine-bearing cargos to and through the Golgi complex.
    D'Angelo G, et al.
    J.Biol.Chem. 2009 11;284(50):34849-60.
  • Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.
    D'Angelo G, et al.
    Nature. 2007 Sep 6;449(7158):62-7

Group

 

Daniela Montariello PostDoc
Serena CapassoPostDoc
Domenico RussoPostDoc
Lucia SticcoPhd Student