Melacini, Guiseppe - McMaster University - Department of Chemistry & Chemical Biology

个人简介

Ph. D. in Biophysical Chemistry, December 1996 University of Milan with external research at the University of California, San Diego Advisor: Professor Murray Goodman Topic: NMR and Molecular Modeling of Peptidomimetics. Application to Collagen and Sandostatin ‘Laurea ’ degree in Physical Chemistry with honors December 1992 University of Milan, Italy; Thesis: 3D-NMR of an Antigenic FMDV Epitope; GPA: 4.0 Employment Professor July 2014 – Present Associate Professor July 2008 – July 2014 Assistant Professor July 2003 – July 2008 Departments of Chemistry & Chemical Biology Department Biochemistry & Biomedical Sciences (joint) McMaster University Lecturer & Assistant Project Scientist, July 1999 to July 2003 Department of Chemistry & Biochemistry University of California, San Diego European Community Postdoctoral Fellow January 1997 to June 1999 Department of NMR Spectroscopy Utrecht University, The Netherlands Advisor: Professor Robert Kaptein Subject: Development of NMR Methods to Study Protein Hydration Honors and Awards NSERC Discovery Accelerator Supplement 2014 McMaster Student Union Teaching Award (Faculty of Science) 2012 Maud Menten CIHR Prize Finalist 2007 Heart & Stroke Found. Canada – New Investigator Award 2006 HSFC Maureen Andrew Top Up Award1 2006 Alzheimer Society of Canada Young Investigator Award 2005 Premier Research Excellence Award 2005 Heart & Stroke Found. Canada - Grant-in-Aid2 2004 American Heart Association - Grant-in-Aid3 2003 NIH Travel stipend for the XIX ICMRBS conference 2000 EMBO fellowship to attend the EMBO NMR Summer School 1997 DOW best chemistry student of the year scholarship 1990, 92 ENICHEM best chemistry student of the year scholarship 1988-90

研究领域

We are primarily interested in two main fields of research: the allosteric conformational switches that control signaling pathways and the early steps of amyloid fibril formation. Allosteric conformational switches in signalling pathways: We are currently mapping the intra-molecular signaling pathways and the dynamic changes that propagate the signal carried by second messengers. So far our work has focused mainly on the exchange protein directly activated by cAMP (EPAC) and on the prototypical receptor for cAMP, i.e. protein kinase A (PKA). To learn more about our work on these topics please follow this pubmed link.* Early steps of amyloid fibril formation: We are currently investigating the mechanism of nucleation and of inhibition of amyloid fibrils. So far our work in this field has mainly focused on the Ab system and on endogenous proteins that inhibit its pathogenic oligomerization (e.g. Human Serum Albumin or HSA). To learn more about our work on this topic please follow this pubmed link and this pubmed link.* These projects have several medical implications ranging from cardiac tumors to Alzheimer’s disease and type II diabetes. These projects also have in common a strong component based on high-field multidimensional multinuclear NMR. When required to address questions relevant to the projects above, we also adapt and customize existing NMR tools and pulse sequences (see for example).

近期论文

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Biochemical and Pharmacological Characterizations of ESI-09 Based EPAC Inhibitors: Defining the ESI-09 "Therapeutic Window". Zhu Y, Chen H, Boulton S, Mei F, Ye N, Melacini G, Zhou J, Cheng X. Sci Rep. 2015 Mar 20;5:9344. doi: 10.1038/srep09344. A tool set to map allosteric networks through the NMR chemical shift covariance analysis. Boulton S, Akimoto M, Selvaratnam R, Bashiri A, Melacini G. Sci Rep. 2014 Dec 8;4:7306. doi: 10.1038/srep07306. Signaling at crossroads: the dialogue between PDEs and PKA is spoken in multiple languages. Moleschi K, Melacini G. Biophys J. 2014 Sep 16;107(6):1259-60. doi: 10.1016/j.bpj.2014.07.051. No abstract available. A mechanism for the auto-inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel opening and its relief by cAMP. Akimoto M, Zhang Z, Boulton S, Selvaratnam R, VanSchouwen B, Gloyd M, Accili EA, Lange OF, Melacini G. J Biol Chem. 2014 Aug 8;289(32):22205-20. doi: 10.1074/jbc.M114.572164. Epub 2014 May 30. Tapping the translation potential of cAMP signalling: molecular basis for selectivity in cAMP agonism and antagonism as revealed by NMR. Boulton S, Akimoto M, VanSchouwen B, Moleschi K, Selvaratnam R, Giri R, Melacini G. Biochem Soc Trans. 2014 Apr;42(2):302-7. doi: 10.1042/BST20130282. Allosteric linkers in cAMP signalling. Akimoto M, Moleschi K, Boulton S, VanSchouwen B, Selvaratnam R, Taylor SS, Melacini G. Biochem Soc Trans. 2014 Feb;42(1):139-44. doi: 10.1042/BST20130257. Review. A novel non-canonical forkhead-associated (FHA) domain-binding interface mediates the interaction between Rad53 and Dbf4 proteins. Matthews LA, Selvaratnam R, Jones DR, Akimoto M, McConkey BJ, Melacini G, Duncker BP, Guarné A. J Biol Chem. 2014 Jan 31;289(5):2589-99. doi: 10.1074/jbc.M113.517060. Epub 2013 Nov 27. Structural basis for cyclic-nucleotide selectivity and cGMP-selective activation of PKG I. Huang GY, Kim JJ, Reger AS, Lorenz R, Moon EW, Zhao C, Casteel DE, Bertinetti D, Vanschouwen B, Selvaratnam R, Pflugrath JW, Sankaran B, Melacini G, Herberg FW, Kim C. Structure. 2014 Jan 7;22(1):116-24. doi: 10.1016/j.str.2013.09.021. Epub 2013 Nov 14. Mapping the interactions between the Alzheimer's Aβ-peptide and human serum albumin beyond domain resolution. Algamal M, Milojevic J, Jafari N, Zhang W, Melacini G. Biophys J. 2013 Oct 1;105(7):1700-9. doi: 10.1016/j.bpj.2013.08.025. In vitro amyloid-β binding and inhibition of amyloid-β self-association by therapeutic albumin. Milojevic J, Costa M, Ortiz AM, Jorquera JI, Melacini G. J Alzheimers Dis. 2014;38(4):753-65. doi: 10.3233/JAD-131169. Ultrasonic and densimetric characterization of the association of cyclic AMP with the cAMP-binding domain of the exchange protein EPAC1. Son I, Selvaratnam R, Dubins DN, Melacini G, Chalikian TV. J Phys Chem B. 2013 Sep 19;117(37):10779-84. doi: 10.1021/jp406451p. Epub 2013 Sep 10. Signaling through dynamic linkers as revealed by PKA. Akimoto M, Selvaratnam R, McNicholl ET, Verma G, Taylor SS, Melacini G. Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14231-6. doi: 10.1073/pnas.1312644110. Epub 2013 Aug 14. Aβ association inhibition by transferrin. Raditsis AV, Milojevic J, Melacini G. Biophys J. 2013 Jul 16;105(2):473-80. doi: 10.1016/j.bpj.2013.03.065. Degradation of MAC13243 and studies of the interaction of resulting thiourea compounds with the lipoprotein targeting chaperone LolA. Barker CA, Allison SE, Zlitni S, Nguyen ND, Das R, Melacini G, Capretta AA, Brown ED. Bioorg Med Chem Lett. 2013 Apr 15;23(8):2426-31. doi: 10.1016/j.bmcl.2013.02.005. Epub 2013 Feb 13. Erratum in: Bioorg Med Chem Lett. 2013 Aug 1;23(15):4469-70. The auto-inhibitory role of the EPAC hinge helix as mapped by NMR. Selvaratnam R, Mazhab-Jafari MT, Das R, Melacini G. PLoS One. 2012;7(11):e48707. doi: 10.1371/journal.pone.0048707. Epub 2012 Nov 21. The projection analysis of NMR chemical shifts reveals extended EPAC autoinhibition determinants. Selvaratnam R, VanSchouwen B, Fogolari F, Mazhab-Jafari MT, Das R, Melacini G. Biophys J. 2012 Feb 8;102(3):630-9. doi: 10.1016/j.bpj.2011.12.030. Epub 2012 Feb 7. cAMP-dependent allostery and dynamics in Epac: an NMR view. Selvaratnam R, Akimoto M, VanSchouwen B, Melacini G. Biochem Soc Trans. 2012 Feb;40(1):219-23. doi: 10.1042/BST20110628. Review. Role of dynamics in the autoinhibition and activation of the exchange protein directly activated by cyclic AMP (EPAC). VanSchouwen B, Selvaratnam R, Fogolari F, Melacini G. J Biol Chem. 2011 Dec 9;286(49):42655-69. doi: 10.1074/jbc.M111.277723. Epub 2011 Aug 26. Mapping allostery through the covariance analysis of NMR chemical shifts. Selvaratnam R, Chowdhury S, VanSchouwen B, Melacini G. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6133-8. doi: 10.1073/pnas.1017311108. Epub 2011 Mar 28. Stoichiometry and affinity of the human serum albumin-Alzheimer's Aβ peptide interactions. Milojevic J, Melacini G. Biophys J. 2011 Jan 5;100(1):183-92. doi: 10.1016/j.bpj.2010.11.037.