Home| Lecturer in Cell Signalling |
Contact details:
| Tel: | +44 20 7882 8423 |
| Fax: | +44 20 7882 2186 |
| Email: | t.maffucci@qmul.ac.uk |
| Address: | Centre for Diabetes, |
Biography
After graduation in Chemistry at the University of Naples, Italy, I worked three years at the Consorzio Mario Negri Sud, Italy and then gained a PhD in Oncology at the University of Chieti, Italy. In 2001 I moved to London and joined Dr Marco Falasca's laboratory at the University College London. We were interested in understanding the mechanisms responsible for insulin resistance. Our attention was focused in particular on signals involving phosphoinositide 3-kinase (PI3K). After one year at the University College London, I started being supported by a Diabetes UK Project Grant to Dr Falasca which lasted three years (Apr 2002-March 2005). I was then awarded with a Diabetes UK RD Lawrence Fellowship (started on Apr 2005). In 2007 I was appointed as a Lecturer in Cell Signalling at the Centre for Diabetes within the Blizard Institute of Cell and Molecular Medicine.
Research Interests
Our research interest is focused on the role of the enzymes phosphoinositide 3-kinases (PI3Ks) and their lipid products in cell signaling. PI3Ks are crucial components of many intracellular signalling pathways and play key roles in different physiological events. Furthermore altered PI3K-dependent pathways are implicated in different diseases including cancer and diabetes. Three classes of PI3Ks exist although the majority of studies have been focused so far on members of class I and their main in vivo product phosphatidylinositol-3,4,5-trisphosphate. However there is currently an increasing interest on the members of class II PI3Ks. We are currently studying the role of these isoforms in different intracellular signalling pathways.
In particular we are studying the role of such enzymes in insulin signaling and diabetes with a particular interest to insulin resistance. Although it has long been known that genetic factors play a determinant role in this disease, the underlying mechanisms responsible for insulin resistance are still poorly defined. One crucial function of insulin is disposal of glucose into adipose and muscle that is obtained through movement of the glucose transporter GLUT4 to cell membrane. This process appears to fail in insulin resistance accompanying several forms of diabetes. We have recently demonstrated that insulin specifically generates the PI3K lipid product phosphatidylinositol-3-phosphate (PtdIns-3-P) that in turn plays a key role in GLUT4 translocation. Our study is currently investigating the mechanism involved in the insulin-dependent generation and the precise mechanism of action of PtdIns-3-P.
Key Publications
• Dominguez V, Raimondi C, Somanath S, Bugliani M, Loder MK, Edling CE, Divecha N, da Silva-Xavier G, Marselli L, Persaud SJ, Turner MD, Rutter GA, Marchetti P, Falasca M, Maffucci T. Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells. J Biol Chem. 2010 Dec 2. [Epub ahead of print]
• Piñeiro R, Maffucci T, Falasca M. The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene. 2010 Sep 13. [Epub ahead of print]
• Falasca M, Chiozzotto D, Godage HY, Mazzoletti M, Riley AM, Previdi S, Potter BVL, Broggini M, Maffucci T. (2010) A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate Br J Cancer 102:104-114.
• Maffucci T, Raimondi C, Abu-Hayyeh S, Dominguez V, Sala G, Zachary IC, Falasca M. (2009) A phosphoinositide 3-Kinase/phospholipase Cgamma1 pathway regulates fibroblast growth factor-induced capillary tube formation PLoS One 4:e8285.
• Falasca M., Hughes W.E., Dominguez V., Sala G, Fostira F, Fang MQ, Cazzolli R, Shepherd PR, James DE, Maffucci T. (2007) The role of phosphoinositide 3-kinase C2 alpha in insulin signaling. J Biol Chem., 282: 28226-28236.
• Maffucci T, Piccolo E, Cumashi A, Iezzi M, Riley AM, Saiardi A Godage HY, Rossi C, Broggini M, Iacobelli S, Potter BVL, Innocenti P, Falasca M. (2005) Inhibition of the PI 3-K/Akt pathway by Inositol pentakisphosphate results in ant-angiogenic and anti-tumour effects. Cancer Res., 65: 8339-8349
• Maffucci T, Cooke FT, Foster FM, Traer CJ, Fry MJ, Falasca M. (2005) Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J Cell Biol., 169: 789-799
Maffucci T, Brancaccio A, Piccolo E, Stein RC, Falasca M. (2003) Insulin induces phosphatidylinositol 3-phosphate formation through TC10 activation. EMBO J., 22: 4178-4189.
• Maffucci T, Razzini G, Ingrosso A, Chen H, Iacobelli S, Sciacchitano S, Quon MJ, Falasca M. (2003) Role of Pleckstrin Homology domain in regulating membrane targeting and metabolic function of insulin receptor substrate-3. Mol. End., 17: 1568-1579
• Marra P, Maffucci T, Daniele T, Di Tullio G, Ikehara Y, Chan EKL, Luini A, Beznoussenko G, Mironov A, De Matteis MA. (2001) The GM130 and GRASP65 Golgi proteins cycle through and define a subdomain of the intermediate compartment. Nat.Cell Biol., 3: 1101–1113
