Giuseppe Melacini

Full professor

phone: +1 905-525-9140
building: A.N. Bourns Science Building
room: Room 156

1997-1999, EU Post-doctoral Fellowship Supervisor: Prof. Robert Kaptein, Department of NMR Spectroscopy, Utrecht University, The Netherlands
1993-1997, Ph.D. in Biophysical Chemistry, University of Milan, with external research at the University of California, San Diego, Thesis: NMR and Molecular Modeling of Peptidomimetics. Application to Collagen and Sandostatin, Supervisors: Prof. Murray Goodman at the University of California, San Diego
1987-1992, ‘Laurea’ degree in Physical Chemistry with honors, University of Milan, Thesis: 3D-NMR of an Antigenic FMDV Epitope, Supervisor: Prof. Mario Farina and Dr. Lucia Zetta

July 2014-present Professor of Chemistry and Chemical Biology, tenured.
July 2018-2023 Cross-appointed to the Department of Biochemistry and Biomedical Sciences. Associate Chair of Graduate Studies in Chemistry

Executive Member, Biophys. Soc. of Canada (role: councilor and chair of Award Committee)
Member, Chemical Institute of Canada
Member, American Chemical Society
Member, The Protein Society
Member, The Biophysical Society
Member, American Society for Biochemistry and Molecular Biology
Member, International Union of Pure and Applied Chemistry

2008-2014 McMaster University, Associate Professor (Tenured and Promoted in July 2008)
2003-2008 McMaster University, Assistant Professor
1999-2003 University of California, San Diego, Lecturer & Assistant Project Scientist , Department of Chemistry & Biochemistry

Discovery Accelerator Supplement Award – NSERC 2014
MSU1 – Teaching award for the Faculty of Science 2012
CIHR – Ranked first in the BMA2 Panel CIHR March 2012 Competition 2012
CIHR – Maud Menten Prize finalist 2007
CIHR – Ranked first in the BMA2 Panel CIHR March 2007 Competition 2007
Heart & Stroke Foundation of Canada – New Investigator Award 2006
Heart & Stroke Foundation of Canada – Maureen Andrew Award3 2006
Alzheimer Society of Canada – Young Investigator Award 2005
Premier’s Research Excellence Award 2005
Heart & Stroke Foundation Canada – Grant-in-Aid Award4 2004
American Heart Association – Grant-in-Aid Award5 2003
NIH – Travel stipend for the XIX ICMRBS conference 2000
EMBO – Fellowship to attend the 2007 EMBO NMR Summer School 1997
DOW – Best chemistry student of the year scholarship 1990 & 1992
ENICHEM – Best chemistry student of the year scholarship 1988 - 1990

Biological Nuclear Magnetic Resonance
Biophysical chemistry with focus on signalling and amyloids

Book Contributions25
1) VanSchouwen B. and Melacini G.*, The INEPT Experiment, Encyclopaedia of Biophysics 2012
2) VanSchouwen B., Akimoto M, Boulton S, Moleschi K, Giri R, and Melacini G.*, Assessing Cyclic Nucleotide Binding Domain Allostery and Dynamics by NMR Spectroscopy, CRC Book on Cyclic Nucleotide Signaling 2014
3) Boulton S., Selvaratnam R., Ahmed R. and Melacini G.* Implementation of the NMR CHEmical Shift Covariance Analysis (CHESCA): A Chemical Biologist’s Approach to Allostery Protein NMR: Methods and Protocols, Methods in Molecular Biology Editor: Ranajeet Ghose – Springer 2018; 1688:391-405
4) VanSchouwen B. and Melacini G.*, Regulation of HCN Ion Channels by Non-Canonical Cyclicm Nucleotides, Handbook of Experimental Pharmacology - Springer 2017; 238:123-133

Publications in the last 5 years
1) Boulton S, Selvaratnam R, Blondeau JP, Lezoualc'h F, Melacini G, Mechanism of Selective Enzyme Inhibition through Uncompetitive Regulation of an Allosteric Agonist, J. Am. Chem. Soc. 2018; 140(30):9624-9637.
2) Baid K, Nellimarla S, Huynh A, Boulton S, Guarné A, Melacini G,Collins SE, Mossman KL.,Direct binding and internalization of diverse extracellular nucleic acid species through the collagenous domain of class A scavenger receptors. Immunol Cell Biol. 2018. doi: 10.1111/imcb.12052
3) Ahmed R, Melacini G. A solution NMR toolset to probe the molecular mechanisms of amyloid inhibitors. Chem Commun (Camb). 2018;54(37):4644-4652.
4) Byun JA, Melacini G. NMR methods to dissect the molecular mechanisms of disease-related mutations (DRMs): Understanding how DRMs remodel functional free energy landscapes. Methods. 2018; 148:19-27.
5) Akimoto, M, VanSchouwen, B, Melacini, G. The Structure of the Apo cAMP-Binding Domain of HCN4: A Stepping Stone towards Understanding the cAMP-Dependent Modulation of the Hyperpolarization-Activated Cyclic-Nucleotide-Modulated (HCN) Ion Channels FEBS J. – 2018; 285 (12):2182-2192.
6) VanSchouwen, B, Melacini, G. Role of Dimers in the cAMP-Dependent Activation of the Hyperpolarization-Activated Cyclic-Nucleotide-Modulated (HCN) Ion Channels J Phys Chem B – 2018 122(8):2177-2190.
7 )Nguyen Y, Boulton S, McNicholl ET, Akimoto M, Harvey H, Aidoo F, Melacini G, Burrows LL. A Highly Dynamic Loop of the Pseudomonas aeruginosa PA14 Type IV Pilin Is Essential for Pilus Assembly. ACS Infect Dis. 2018; 4(6):936-943
8) Rashi, A, Milojevic J, Melacini G. Functional Dynamics in Cyclic Nucleotide Signaling and Amyloid Inhibition BBA - Proteins and Proteomics 2017, 1865(11 Pt
9) Ahmed R, VanSchouwen B, Jafari N, Ni , Ortega, Melacini G, Molecular Mechanism for the EGCG-Induced Toxic to Non-Toxic Remodeling of Aβ Oligomers
J. Am. Chem. Soc. 2017 139(39):13720-13734.
10) Algamal M, Ahmed R, Jafari N, Ahsan B, Ortega J, Melacini G. Atomic-Resolution Map of the Interactions between an Amyloid Inhibitor Protein and Amyloid Beta
(Aβ) Peptides in the Monomer and Protofibril States. J Biol Chem. 2017 292(42):17158-17168.
11) Boulton S, Akimoto M, Akbarizadeh S, Melacini G, Free Energy Landscape Remodeling of the Cardiac Pacemaker Channel Explains the Molecular Basis of Familial Sinus Bradycardia J. Biol. Chem. 2017 292(15):6414-6428.
12) Campbell JC, VanSchouwen B, Lorenz R, Sankaran B, Herberg FW, Melacini G, Kim C.Crystal structure of cGMP-dependent protein kinase Iβ cyclic nucleotide-binding-B domain: Rp-cGMPS complex reveals an apo-like, inactive conformation. FEBS Lett. 2017 591(1):221-230
13) VanSchouwen B, Melacini G. Structural Basis of Tonic Inhibition by Dimers of Dimers in Hyperpolarization-Activated Cyclic-Nucleotide-Modulated (HCN) Ion Channels. J Phys Chem B. 2016 120(42):10936-10950.
14) Almawi AW, Matthews LA, Larasati, Myrox P, Boulton S, Lai C, Moraes T, Melacini G, Ghirlando R, Duncker BP, Guarné A. Crystal structure of Rad53 bound to Dbf4 and Cdc7. Sci Rep. 2016;6:34237.
15) VanSchouwen B, Melacini G.Cracking the allosteric code of NMR chemical shifts. Proc Natl Acad Sci U S A. 2016;113(34):9407-9.
16) Jafari N, Ahmed R, Gloyd M, Bloomfield J, Britz-McKibbin P, Melacini G. Allosteric Sensing of Fatty Acid Binding by NMR: Application to Human Serum Albumin. J Med Chem. 2016;59(16):7457-65
17) Boulton S, Melacini G. Advances in NMR Methods To Map Allosteric Sites: From Models to Translation. Chem Rev. 2016;116(11):6267-304.
18) Byun JA, Melacini G. Disordered Regions Flanking Ordered Domains Modulate Signaling Transduction. Biophys J. 2015;109(12):2447-8.
19) Akimoto M, Tyler E, Ramkissoon A, Moleschi K, Taylor SS, Melacini G, Mapping the Free Energy Landscape of PKA Inhibition and Activation: A Double-Conformational Selection Model for the Tandem cAMP-Binding Domains of PKA RIα. PLOS Biology, 2015 13(11):e1002305.
20) VanSchouwen B, Selvaratnam R, Giri R, Lorenz R, Herberg FW, Kim C, Melacini G. Mechanism of cAMP Partial Agonism in Protein Kinase G (PKG). J Biol Chem. 2015 290(48):28631-41.
21) Moleschi KJ, Akimoto M, Melacini G. Measurement of State-Specific Association Constants in Allosteric Sensors through Molecular Stapling and NMR. J Am Chem Soc. 2015 137(33):10777-85.
22) Tomaselli S, Pagano K, Boulton S, Zanzoni S, Melacini G, Molinari H, Ragona L. Lipid binding protein response to a bile acid library: a combined NMR and statistical approach. FEBS J. 2015 282(21):4094-113.
23) Fogolari F, Corazza A, Fortuna S, Soler MA, VanSchouwen B, Brancolini G, Corni S, Melacini G, Esposito G. Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations. PLoS One. 2015 Jul 15;10(7):e0132356.
24) VanSchouwen B, Akimoto M, Sayadi M, Fogolari F, Melacini G, Role of Dynamics in the Auto-Inhibition and Activation of the Hyperpolarization-Activated Cyclic-
Nucleotide-Modulated (HCN) Ion Channels. J Biol Chem. 2015, 290(29):17642-54.
25) Zhu Y, Chen H, Boulton S, Mei F, Ye N, Melacini G, Zhou J, Cheng X. Biochemical and Pharmacological Characterizations of ESI-09 Based EPAC Inhibitors: Defining the ESI-09 "Therapeutic Window". Nature Sci Rep. 2015;5:9344.

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