Charles Deber

Professor Charles Deber received his B.Sc. in at the Polytechnic Institute of Brooklyn with Murray Goodman; his PhD at MIT under Arthur C. Cope; and was a post-doctoral fellow and then research associate with Elkan Blout at Harvard Medical School. He completed his training with a stint at the Enzyme Institute at the University of Wisconsin, Madison, with enzymologist Henry Lardy, working on ionophore-mediated calcium transport.

At Sickkids, Dr. Deber’s research has featured an experimental program utilizing natural and de novo designed hydrophobic peptides and proteins, and the application of spectroscopic techniques in combination with molecular biology and molecular modeling, that aims at increasing our understanding as to how amino acid sequence influences the interactions of peptides and proteins within membranes, and induces disease states that are derived from misfolding of membrane proteins.  His work aims at establishing fundamental conclusions that correlate peptide/protein structure with function, and thereby to provide a window to understand and tackle a number of important medical problems.  

Research

Dr. Deber’s laboratory has implemented the use of a variety of techniques, including molecular biology, protein biochemistry, bioinformatics, chemical synthesis, spectroscopy, and molecular modeling that, in combination, have proven to be productive for defining key features of protein transmembrane (TM) segments that span cellular bilayers, and act to fold the protein into its functional structure. These principles are currently being applied to understand larger questions of membrane-based peptide and protein function, and peptide/membrane interactions, as described below for several specific research areas currently active in his laboratory.

1. Development of novel antibiotic peptides against bacterial biofilms:   Biofilm formation by bacteria is characterized by the overproduction of exopolysaccharides (EPS) – long-chain sugar polymers secreted by opportunistic pathogens such as Pseudomonas aeruginosa – and reduces bacterial killing by conferring tolerance to conventional antibiotics. We are coupling peptide chemistry and biology with biophysical studies of de novo designed cationic antimicrobial peptides (CAPs) mechanisms to facilitate the development of lead peptides that portend the best success for therapeutic intervention.  
2. Mutations in membrane proteins as determinants of genetic diseases; the case of cystic fibrosis: Our lab has successfully expressed helix-loop-helix constructs ('helical hairpins') corresponding to various TM helices from CFTR – the cystic fibrosis gene product. We are undertaking to determine systematically how CF-disease causing mutations affect local CFTR structure and folding – and in the longer range, to use this information to  identify molecular targets for corrective interventions.   
3. Design of peptide-based inhibitors of bacterial multidrug resistance:  We are examining the molecular mechanism as to how clinically significant bacterial resistance to drugs and cytotoxic compounds is catalyzed by proteins embedded in the bacterial cell membrane.  Using this information, we are synthesizing peptides that correspond to selected TM helices of various bacterial efflux proteins to design peptides that inhibit their efflux capacity. 
4. Defining ‘hydrophobicity’ in membrane environments:  We are examining how sequence and composition affect the relative hydrophobicity and helicity of incipient TM helices, and whether hydrophobicity is determined by a value averaged over the full helix length, or by localized areas of high hydrophobic character.

Education

• 1959–62: B.Sc., Polytechnic Institute of Brooklyn, Brooklyn, NY  
• 1962–67: PhD., Massachusetts Institute of Technology, Cambridge, MA 
• 1969–70: Post-doctorate fellow, Harvard Medical School, Boston, MA 
• 1971–74: Research Associate, Harvard Medical School, Boston,, MA 
• 1975–76: Research Scientist, Enzyme Institute, University of Wisconsin, Madison, WI 

Experience

• 1976–1980: Assistant Professor, University of Toronto,  Department of Biochemistry 
• 1976–1980: Scientist, Research Institute, Hospital for Sick Children, Biochemistry Research 
• 1981–Present: Senior Scientist, Research Institute, Molecular Medicine, Hospital for Sick Children 
• 1981–1984: Associate Professor, University of Toronto, Department of Biochemistry 
• 1985–Present: Professor, University of Toronto, Department of Biochemistry  

Achievements

• 1996: W.T. Aikins Award for Excellence in Undergraduate Teaching, University of Toronto, Faculty of Medicine 
• 2000: Vincent du Vigneaud Award for Outstanding Achievements in Peptide Research, American Peptide Society
• 2001: Elected Fellow of the Royal Society of Canada (FRSC) 
• 2001: Elected to Canadian Who's Who 
• 2009: Goodman Scientific Excellence & Mentorship Award, American Peptide Society 
• 2017: R. Bruce Merrifield Award, “recognizing the highest level of scientific creativity in peptide research”, American Peptide Society