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About Sickkids
About SickKids

Charles Deber, PhD, FRSC

Research Institute
Senior Scientist
Molecular Medicine

University of Toronto

Phone: 416-813-5924 (office)
Fax: 416-813-5005
e-mail: deber@sickkids.ca

Brief Biography

Charles Deber was born and raised in Brooklyn, New York.  He received his B.Sc. from the Polytechnic Institute of Brooklyn (working with Murray Goodman); his PhD in Organic Chemistry from MIT (Arthur Cope); and was a post-doctoral fellow at Harvard Medical School (Elkan Blout) and research associate at the University of Wisconsin-Madison Enzyme Institute (Henry Lardy).  He joined the Research Institute at The Hospital for Sick Children in 1976, with cross-appointment to the University of Toronto Department of Biochemistry. 

Dr. Deber was recognized by the American Peptide Society with the Vincent du Vigneaud Award in 2000 for “Outstanding Career Achievements in Peptide Research,” and the Murray Goodman Scientific Excellence and Mentorship Award in 2009.  At U of T, he received the W.T. Aikins Award for excellence in undergraduate teaching in the Faculty of Medicine. Dr. Deber was elected in 2001 as a Fellow of the Royal Society of Canada (FRSC). 

Dr. Deber’s research utilizes natural and de novo designed hydrophobic peptides and proteins, and the application of spectroscopic techniques, molecular modeling, and bioinformatics, to investigate the interactions and structures of peptides and proteins within membranes, how membrane-embedded mutations underlie protein misfolding diseases, and how knowledge gained from these studies can be applied to the development of membrane-interactive peptide therapeutics.

Mailing Address 

The Hospital for Sick Children
Research Institute, Molecular Structure & Function
Peter Gilgan Centre for Research & Learning (PGCRL), Room 20.9712
686 Bay Street
Toronto, ON M5G 0A4

Academic Background

  • B.Sc., Polytechnic Institute of Brooklyn (1962)
  • PhD, Massachusetts Institute of Technology (1967)
  • Post-doctoral fellow, Harvard Medical School (1968-70)

Research Interests

Peptide and Protein Structure in Membranes: From Folding to Drug Discovery 

Membrane proteins are required for cellular processes such as nutrient uptake signaling, and cell-cell communication. Through a series of model and designed membrane protein and peptide constructs, our lab studies how membrane proteins assemble to produce their biologically functional structures. Understanding these principles and mechanisms allows us to pinpoint sequence features required for membrane proteins to fold, and to use these to design peptide therapeutics. Several projects are underway: 

1. Mutations in membrane proteins as the source of genetic diseases: The case of cystic fibrosis 

Protein-mediated human diseases are caused by mutations that change packing and/or electrostatic interactions needed for normal protein folding and function. For example, the most common cause of cystic fibrosis (CF) is deletion of the nucleotide binding domain residue F508 in the cystic fibrosis transmembrane conductance regulator (CFTR), which causes the protein to misfold. In addition to delta-F508, nearly 2,000 mutations have been identified by the CF Genetic Analysis Consortium – of which hundreds occur in the membrane domain of CFTR. Complete understanding of how mutations in membrane domains lead to CFTR misfolding is needed to develop better treatments. To this end, our lab has successfully expressed in E. coli helix-loop-helix constructs (‘hairpins’) corresponding to the membrane-spanning sequences of CFTR, and uses various spectroscopic methods such as fluorescence and circular dichroism to investigate their interactions with membrane environments. Our research focuses on both membrane-based sites and the intervening loops where CF-phenotypic mutations occur, with the goal of assessing the structural impact of point mutations on hairpin folding.

CFTR TM3/4 hairpins
Secondary structure conversion in CFTR TM3/4 hairpins. Introduction of a Pro-Gly β-turn-promoting couplet into the wild type loop creates a steric clash (D), and converts the hairpin from a helix-loop-helix structure (A) to an oligomerized β-sheet structure (B,C) that interacts with lipid bilayers (E).

2. Peptide inhibitors of bacterial multidrug resistance

Bacterial resistance to drugs and toxic compounds is caused by pumps embedded in the bacterial cell membrane. The small multidrug resistance (SMR) protein family pumps drugs out of bacteria only when at least two inactive monomers assemble within the membrane. SMR monomers encompass four transmembrane (TM) α-helices connected by three extracellular short loops, and must use their TM helices to assemble. Disruption of these helix-helix interactions will therefore impair the ability of bacteria to efflux drugs. We have identified the key SMR helix-helix assembly motifs on TM4, and created peptide mimics of this helix-helix interface that reduce SMR activity in vitro and in vivo. These peptides are now lead compounds for development of peptide therapeutics with broad-spectrum inhibition activity. Peptide design concentrates on shortened analogs and ‘stapled’ peptides, where the functional conformation of the inhibitor peptide is locked into a ring.

Proposed drug efflux inhibition model
Proposed drug efflux inhibition model for small multidrug resistance proteins (SMRs). The transmembrane (TM) dimerization site on SMR helix 4 is a “hotspot for inhibition,” A designed TM4 peptide competes for the dimerization site, producing monomers, and rendering the protein unable to transport a typical substrate.

3. Antibiotic peptides active against bacterial biofilms

Chronic bacterial infections that occur in CF patients are difficult to treat because bacteria are resistant to existing antibiotics. Treating infections becomes even more difficult when bacterial attach to tissues or to other surfaces by producing exopolysaccharides (EPS), resulting in bacterial biofilms that are nearly impossible to eliminate. New ways to treat resistant infections are thus urgently needed. We have de novo designed and synthesized a new category of cationic antimicrobial peptides (CAPs) that effectively eliminate Pseudomonas aeruginosa – the primary cause of lung disease and mortality in CF patients. These new CAPs – epitomized by sequences such as KKKKKK-AAFAAWAAFAA-NH2 (termed 6K-F17), and featuring our patented implementation of charge segregation from the hydrophobic core, kill bacteria by destroying cell membranes rather than by targeting a specific protein or biochemical process. We are currently working to identify the best lead CAPs by testing their activity against resistant P.aeruginosa strains isolated from CF patients, and determining safety and pharmacokinetics in animal models. These studies will greatly advance our discovery toward the goal of clinical trials in CF patients.

Comparison of proposed mechanisms
Comparison of proposed mechanisms of action between the natural cationic antimicrobial peptide (CAP) magainin II amide (left) and the designed CAP 6K-F17 (sequence shown) (right). By segregating positive charges from the hydrophobic core segment of the peptide – instead of placing them on opposite faces as in the amphipathic magainin II amide – the membrane-destructive power of the designed CAPs is enhanced through their ability to “grip” and then “dip” into the anionic bacterial membrane, rather than being anchored into its surface.

4. Peptide models to study translocon recognition of transmembrane protein segments

Newly-synthesized helical membrane proteins insert into the lipid bilayer in a stepwise fashion through which individual helices are inserted sequentially with the aid of the translocon, an α-helical protein located in the plasma membrane of prokaryotes and the ER of eukaryotes. The translocon forms a channel through which passing nascent polypeptide segments partition laterally into the lipid bilayer. Insertion by the translocon is thought to be a biophysical event that can be modeled by in vitro methods that measure partitioning in membrane environments. To address these ideas experimentally, we are designing and synthesizing several series of peptides of length typically required to span a biological membrane, and using biophysical analysis to assess the relationship between sequence and partitioning in vitro.

Schematic model of translocon- vs. HPLC-mediated helix insertion
Schematic model of translocon- vs. HPLC-mediated helix insertion. (A) The translocon crystal structure (T. thermophilus SecYE; PDBID: 2ZJS) is shown in red, inserting an ideal helix (blue). In (B), the protein helix partitions from an HPLC polar mobile phase into the C18 acyl regions (orange) of the column’s solid support, paralleling a bilayer insertion process.


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 — Murray Goodman Award for Scientific Excellence and Mentorship in Peptide Science
2017 — R. Bruce Merrifield Award of  American Peptide Society for Career-Long Scientific Creativity in Peptide Science


Stone TA, Deber CM: Therapeutic design of peptide modulators of protein-protein interactions in membranes (Review).  Biochim. Biophys. Acta – Biomembranes 1859, 577-585 (2017).

*Stone TA, *Schiller N, Workewych NV, von Heijne G, Deber CM:  Hydrophobic clusters raise the threshold hydrophilicity for insertion of transmembrane sequences in vivo (*co-first authors). Biochemistry 55, 5772-5779 (2016).

Ng DP, Deber CM:  Modulating transmembrane alpha-helix interactions through pH-sensitive boundary residues. Biochemistry 55, 4306-4315 (2016).

Nadeau VG, Deber CM:  Structural impact of proline mutations in the loop region of an ancestral membrane protein. Peptide Science 106, 37-42 (2016).

Nadeau VG, Gao A, and Deber CM:  Design and characterization of a membrane protein unfolding platform in lipid bilayers. PLoS ONE 10, e0120253 (2015).  doi:10.1371/journal.pone.0120253.

Deber CM, Ng DP:  Helix-helix interactions:  Is the medium the message?  (Invited commentary ‘Preview’).  Structure (Cell Press) 23, 437-438 (2015).

Stone TA, Schiller N, von Heijne G, Deber CM:  Hydrophobic blocks facilitate lipid compatibility and translocon recognition of transmembrane protein sequences. Biochemistry 54, 1465-1473 (2015).

Bellmann-Sickert K, Stone TA, Poulsen BE, Deber CM:  Efflux by small multidrug resistance proteins is inhibited by membrane-interactive helix-stapled peptides. J. Biol. Chem. 290, 1752-1759 (2015).

Ng DP and Deber CM.:  Terminal residue hydrophobicity modulates transmembrane  helix-helix interactions. Biochemistry 53, 3747-3757 (2014).

Wang J, Rath A, and Deber CM.:  Functional response of the small multidrug resistance protein EmrE to mutations in transmembrane helix 2. FEBS Lett. 588, 3720-3725 (2014).

Nadeau VG and Deber CM: Loop sequence dictates the secondary structure of a human membrane protein hairpin. Biochemistry 52, 2419-2426 (2013).

Rath A, Cunningham F, and Deber CM:  Acrylamide concentration determines direction and magnitude of gel shifts of helical membrane proteins.  Proc. Natl. Acad. Sci. USA 110, 15668-15673 (2013).

Yin LM, Lee,S, Mak JSW, Helmy AS, and Deber CM:  Differential binding of L- vs. D-isomers of cationic antimicrobial peptides to the biofilm exopolysaccharide alginate.  Protein and Peptide Letters 20, 843-847 (2013).

Strandberg L., Cui X, Rath A, Liu X, Silverman E, Vinayakumar S, Ackerley C, Bin Su B, Yan JY, Capecchi M, Biavati L, Accorroni A, Yuen W, Quattrone F, Lung K, Jaeggi E, Deber CM, and Hamilton RM:  α1G T-type calcium channel is expressed in human fetal hearts and has an extracellular epitope bound by autoantibodies from congenital heart block maternal sera.  PLoS ONE 8, e72668 (2013); doi:10.1371/journal.pone.0072668. 

Rath A and Deber CM:  Design of transmembrane peptides: coping with sticky   situations.  In “Membrane Proteins:  Folding, Association, and Design” (G. Ghirlanda, A. Senes and J. Walker, eds.), Humana Press, Springer Publishing Co., New York, NY.  Methods in Molecular Biology 1063, 197-210 (2013). 

Patel PC, Lee HSW, Ming AYK, Rath A, Deber CM, Yip CM, Rocheleau JV and Gray-Owen SD:  Inside-out signaling promotes dynamic changes in the CEACAM1 oligomeric state to control its cell adhesion properties. J. Biol. Chem. 288, 29654-29669 (2013).

Alvares RDA, Tulumello DV, Macdonald PM, Deber CM, Prosser RS: The effect of a polar amino acid substitution on helix formation and aggregate size along the detergent-induced peptide folding pathway. Biochim. Biophys. Acta - Biomembranes 1828, 373-381 (2013).

Rath A, Deber CM:  Correction factors for membrane protein molecular weight readouts on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analytical Biochemistry 434, 67-72 (2013).

Tulumello DV, Johnson RM, Isupov I, Deber CM:  Design, expression, and purification of de novo transmembrane ‘hairpin’ peptides”.  Biopolymers (Peptide Science) 98, 546-556 (2012).

Nadeau VG, Rath A, Deber CM:  Sequence hydropathy dominates membrane protein response to detergent solubilization.  Biochemistry 51, 6228-6237 (2012).

Rotstein BH, Winternheimer DJ, Yin LM, Deber CM, Yudin AK:  Thioester-Isocyanides:  Versatile reagents for the synthesis of cycle-tail peptides.  Chemical Communications (Royal Soc. Chem.) 48, 3775-3777 (2012).

Poulsen BE, Deber CM:  Drug efflux by a small multidrug resistance protein is inhibited by a transmembrane peptide.  Antimicrobial Agents & Chemother. 56, 3911-3916 (2012).

Yin LM, Edwards MA, Li J, Yip CM, Deber CM:  Roles of hydrophobicity and charge distribution of cationic antimicrobial peptides in peptide-membrane interactions. J. Biol. Chem. 287, 7738-7745 (2012).

Tulumello DV, Deber CM:  Efficiency of detergents at maintaining membrane protein structures in their biologically relevant forms.  Biochim. Biophys. Acta - Biomembranes 1818, 1351-1358 (2012).

Rath A, Deber CM:  Protein structure in membrane domains (Invited review). Ann. Rev. of Biophysics. 41,135-155 (2012).

Ng DP, Poulsen BE, Deber CM:  Membrane protein misassembly in disease. Biochim. Biophys. Acta – Biomembranes 1818, 1115-1122 (2012).

Mulvihill CM, Deber CM:  Structural basis for misfolding at a disease phenotypic position in CFTR:  comparison of TM3/4 helix-loop helix constructs with TM4 peptides.  Biochim. Biophys. Acta - Biomembranes 1818, 49-54 (2012).

Tulumello DV, Deber CM:  Membrane protein folding in detergents. In Methods in Protein Biochemistry (H. Tschesche, ed.), de Gruyter Publishers, Berlin, Germany; pp. 23-45 (2011).

Poulsen BE, Cunningham F, Lee KY, Deber CM:  Modulation of substrate efflux in bacterial small multidrug resistance proteins by mutations at the dimer interface. J. Bacteriology 193, 5929-5935 (2011).

Tulumello DV, Deber CM:  Positions of polar amino acids alter interactions between transmembrane segments and detergents. Biochemistry 50, 3928-3935 (2011).

Cunningham F, Poulsen BE, Ip W, Deber CM: Beta-branched residues adjacent to GG4 motifs promote the efficient association of glycophorin A transmembrane helices. Peptide Science 96, 340-347 (2011).

Norholm MHH, Cunningham F, Deber CM, von Heijne G:  Converting a marginally hydrophobic globular protein into a membrane protein.  J. Molecular Biology 407, 171-179 (2011).

Rath A, Nadeau VG, Poulsen BE, Ng DP, Deber CM:  Novel hydrophobic standards for membrane protein molecular weight determinations via sodium dodecyl sulfate – polyacrylamide gel electrophoresis. Biochemistry 49, 10589-10591 (2010).

Mulvihill CM, Deber CM:  Evidence that the translocon may function as a hydropathy partitioning filter. Biochim Biophys Acta – Biomembranes 1798, 1995-1998 (2010).

Ng DP, Deber CM:  Modulation of the oligomerization of myelin proteolipid protein (PLP) by transmembrane helix interaction motifs.  Biochemistry 49, 6896-6902 (2010).

Deber CM, Brodsky B, Rath A:  Proline residues in proteins.  In Encyclopedia of Life Sciences, John Wiley & Sons Ltd., Chichester, U.K. (2010).

Ng DP, Deber CM:  Deletion of a terminal residue disrupts oligomerization of a transmembrane alpha-helix.  Biochem. Cell Biol. 88, 339-345 (2010).

Tulumello DV, Deber CM:  SDS micelles as a membrane-mimetic environment for transmembrane segments. Biochemistry 48, 12096-12103 (2009).

Grant CV, Yang Y, Glibowicka M, Wu CH, Park SH, Deber CM, Opella SJ:  A modified Alderman-Grant coil makes possible an efficient cross-coil probe for high field solid-state NMR of lossy biological samples. J. Mag. Resonance 201, 87-92 (2009).

Kim Chiaw P, Gonska T, Huan L-J, Gagnon S, Ly D, Sweezey N, Rotin D, Deber CM, Bear CE:  Functional rescue of deltaF508CFTR by peptides designed to mimic sorting motifs. Chemistry & Biology 16, 520-530 (2009).

Cunningham F, Rath A,  Deber CM:  Hydrophobic peptide segments in soluble proteins competent for membrane insertion:  role in amyloidogenesis.  Adv. Exp. Med. Biol. 611, 299-300 (2009).

Cheung JC, Kim Chiaw P, Deber CM, Bear CE:  A novel method for cytosolic delivery of peptide cargo.  J. Controlled Release 137, 2-7 (2009).

Rath A, Tulumello DV, Deber CM: Peptide models of membrane protein folding. (‘Current Topics’ Review) Biochemistry 48, 3036-3045 (2009).

Poulsen BE, Rath A, Deber CM: The assembly motif of a bacterial small multidrug resistance protein. J. Biol. Chem. 284, 9870-9875 (2009).

Rath A, Glibowicka M, Nadeau VG, Chen G, Deber CM: Detergent binding explains anomalous SDS-PAGE migration of membrane proteins. Proc. Natl. Acad. Sci. USA 106, 1760-1765 (2009).

Cunningham F, Rath A, Johnson RM, Deber CM: Distinctions between hydrophobic helices in soluble proteins and transmembrane segments as factors in protein sorting. J. Biol. Chem. 284, 5395-5402 (2009).

A detailed list of Dr. Deber's publications can be found on Pub Med. »»

Intellectual Property

  • Novel Peptide Antibiotics

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