Charles Haynes

Contact Information
Michael Smith Laboratories
NEC #231, 2185 East Mall
Vancouver, BC, Canada, V6T 1Z4
Tel: 1-604-822-5136
Fax: 1-604-822-2114
Email: israels@chbe.ubc.ca

Current Positions

  • Professor, Chemical and Biological Engineering, Applied Science.
  • Professor, Michael Smith Laboratories, Science.
  • Canada Research Chair in Interfacial Biotechnology.

Research Interests

Purity and purification costs are becoming important issues in biotechnology as the industry matures and competitive products reach the marketplace. The primary objective of Dr. Haynes’ research is to develop new natural and recombinant-protein purification processes based on high-affinity interactions between target proteins or drugs and separation media. Fundamental research focuses on development of new instrumentation, particularly microcalorimetry and UV-resonance Raman spectroscopy, for quantifying the delicate energetics of biological interactions and binding. When engineered properly, molecular genetics techniques provide a robust method for purifying recombinant proteins from the complex aqueous solutions in which they are produced. Dr. Haynes, in collaboration with Drs. Kilburn and Warren of the Microbiology department, is interested in purification strategies which use the cellulose binding domains (CBD’s) of Cellulomonas fimi cellulases as affinity tags. Genetic or chemical linkage of a CBD to the target protein creates a fusion protein which binds strongly to cellulose and retains the biological activity of the fusion partner. Recovery of the target protein is then achieved through either a modest change in system variables or enzymatic cleavage of the polypeptide backbone at the protein/CBD linkage. Many protein purification processes rely on controlled and/or well characterized adsorption at solid-liquid or liquid-liquid interfaces. For instance, chromatographic separations, such as hydrophobic, displacement and ion-exchange chromatographies, are based on differences in binding affinities of proteins for the support material. Understanding protein adsorption at synthetic surfaces is also critical to the development of improved biomaterials for use in artificial organs, vascular grafts, haemodialysis cartridges, blood bags, etc. A second interest of Dr. Haynes concerns thermodynamic (including electrostatic) aspects of protein adsorption with the aim of revealing general principles and resolving the dominant forces governing adsorption processes. Synthesis of pharmaceutical drugs often requires precursors of specified chirality. However, chemical syntheses of drug precursors, such as amino acids, typically yield racemic mixtures. Dr. Haynes is involved in the development of large-scale, continuous processes for separating mixtures of chiral enantiomers. Research to date has involved the fabrication and characterization of ligands which selectively separate chiral therapeutics with a single hydrophilic chiral center.

Publications

  1. Kalathottukaren MT*, Haynes CA, Kizhakkedathu JN. (2018). Approaches to prevent bleeding associated with anticoagulants: current status and recent developments. Drug Deliv Transl Res. 8: 928-944.
  2. Kalathottukaren MT, Creagh AL, Abbina S, Lu G, Karbarz MJ, Pandey A, Conley PB, Kizhakkedathu JN#, Haynes C# (# equal senior authors). (2018). The Comparison of Reversal Activity and Mechanism of Action of UHRA, Andexanet and PER977 on Heparin and Oral FXa Inhibitors. Blood Advances. 2(16): 2104-2114.
  3. Manu T. Kalathottukaren*, Libin Abraham ,Piyushkumar R. Kapopara, Benjamin Lai*, Rajesh Shenoi*, Federico Rosell, Edward M. Conway, Edward L. Pryzdial, James H. Morrissey, Charles A. Haynes and Jayachandran N. Kizhakkedathu. (2017). Alteration of blood clotting and lung damage by protamine are avoided using the heparin and polyphosphate inhibitor, UHRA. Blood. 129(10): 1368-1379.
  4. Kalathottukaren MT*, Abbina S*, Yu K*, Shenoi RA*, Creagh AL, Haynes C, Kizhakkedathu JN. (2017). A polymer therapeutic having universal heparin reversal activity: molecular design and functional mechanism. Biomacromolecules. 18(10): 3343.
  5. Hamilton JL*, Ul-haq MI*, Creagh AL, Haynes CA, Kizhakkedathu JN. (2017). Iron Binding and Iron Removal Efficiency of Desferrioxamine Based Polymeric Iron Chelators: Influence of Molecular Size and Chelator Density. Macromolecular Bioscience. 17: 1600244.
  6. Yu K, Creagh AL, Haynes CA, Kizhakkedathu JN. (2016). Modulation of Multivalent Protein Binding on Surfaces by Glycopolymer Brush Chemistry. Methods Mol Biol. 1367: 183-193.
  7. Manu Thomas Kalathottukaren, Libin Abraham, Benjamin F.L. Lai, Rajesh A. Shenoi, Federico I. Rosell, Edward L.G. Pryzdial, James H. Morrissey, Charles A. Haynes and Jayachandran N. Kizhakkedathu. (2016). Alteration of clotting and clot morphology by protamine are avoided using the heparin and polyphosphate inhibitor, UHRA. Blood. 0: 1-10. 129(10): 1368–1379.
  8. Lund H, Hughesman C, McNeil K, Clemens S, Hocken K, Pettersson R, Karsan A, Foster L, Haynes C. Initial Diagnosis of Chronic Myelogenous Leukemia Based on Quantification of M-BCR Status Using Droplet Digital PCR. Anal Bioanal Chem. 2016 Feb;408(4):1079-94. PMID: 26631023.
  9. Lund H, Hughesman C, Fakhfakh K, McNeil K, Clemens S, Hocken K, Pettersson R, Karsan A, Foster L, Haynes C. Initial Diagnosis of ALK-Positive Non-Small-Cell Lung Cancer Based on Analysis of ALK Status Utilizing Droplet Digital PCR. Anal Chem. 2016 May 3;88(9):4879-85. PMID: 27043019.
  10. Bidshahri R, Attali D, Fakhfakh K, McNeil K, Karsan A, Won J, Wolber R, Bryan J, Hughesman C, Haynes C. Quantitative detection and resolution of BRAF V600 status in colorectal cancer using droplet digital PCR and a novel wild-type negative assay. J Mol Diagn. 2016 Mar;18(2):190-204. PMID: 26762843.
  11. Ouellet E, Foley JH, Conway EM, Cheung KC, Haynes CA. Hi-Fi SELEX: A high-fidelity digital-PCR based therapeutic aptamer discovery platform. Biotechnology and Bioengineering 2015 Aug 112(8):1506-22 PMID: 25727321.
  12. F. Cawthray, D. M. Weekes, O. Sivak, A. L. Creagh, F. Ibrahim, M. Iafrate, C. A. Haynes, K. M. Wasan, C. Orvig.  In vivo Study and Thermodynamic Investigation of Two Lanthanum Complexes, La(dpp)3 and La(XT), for the Treatment of Bone Resorption Disorders. Chem. Sci. 2015, 6, 6439-6447.
  13. F. Cawthray, A. L. Creagh, C. A. Haynes, C. Orvig. Ion Exchange in Hydroxyapatite with Lanthanides. Inorg. Chem. 2015, 54, 1440-1445.
  14. Shenoi,RA.*; Kalathottukaren, MT*; Travers, RJ; Lai, B.*; Creagh, AL.; Lange, D.; Chew, B.; Du, C.; Brooks, DE.; Carter, C.;Morrissey, JH.; Haynes CA.; Kizhakkedathu JN. (2014). Affinity-based design of a synthetic universal reversal agent for heparin anticoagulants. Science Translational Medicine. 6: 260ra150.
  15. Huft J, Haynes CA, Hansen CL. Rapid Fabrication of High-Quality Microfluidic Solid Phase Chromatography Columns. Anal Chem. 2012 Dec 12.
  16. Ghosh P, Vahedipour K, Lin M, Vogel JH, Haynes CA, von Lieres E. Zonal rate model for axial and radial flow membrane chromatography. Part I: Knowledge transfer across operating conditions and scales. Biotechnol Bioeng. 2012 Oct 23.
  17. Francis P, von Lieres E, Haynes CA. Zonal rate model for stacked membrane chromatography. I: characterizing solute dispersion under flow-through conditions. J Chromatogr A. 2011 Aug 5;1218(31):5071-8.
  18. Hughesman CB, Turner RF, Haynes CA. Role of the heat capacity change in understanding and modeling melting thermodynamics of complementary duplexes containing standard and nucleobase-modified LNA. Biochemistry. 2011 Jun 14;50(23):5354-68.
  19. Singhal A, Haynes CA, Hansen CL. Microfluidic Measurement of Antibody-Antigen Binding Kinetics from Low-Abundance Samples and Single Cells. Anal Chem. 2010 Sep 21.
  20. Kavoosi M, Creagh AL, Turner RF, Kilburn DG, Haynes CA. Direct measurement of the kinetics of CBM9 fusion-tag bioprocessing using luminescence resonance energy transfer. Biotechnol Prog. 2009 May-Jun;25(3):874-81.
  21. Francis P, Haynes CA.Scale-up of controlled-shear affinity filtration using computational fluid dynamics. Biotechnol J. 2009 May;4(5):665-73.
  22. Bordbar AK, Creagh AL, Mohammadi F, Haynes CA, Orvig C. Calorimetric studies of the interaction between the insulin-enhancing drug candidate bis(maltolato)oxovanadium(IV) (BMOV) and human serum apo-transferrin. J Inorg Biochem. 2009 Apr;103(4):643-7.
  23. Shaner RL, Allegood JC, Park H, Wang E, Kelly S, Haynes CA, Sullards MC, Merrill AH Jr. Quantitative analysis of sphingolipids for lipidomics using triple quadrupole and quadrupole linear ion trap mass spectrometers. J Lipid Res. 2009 Aug;50(8):1692-707.
  24. Coad BR, Kizhakkedathu JN, Haynes CA, Brooks DE. Synthesis of Novel Size Exclusion Chromatography Support by Surface Initiated Aqueous Atom Transfer Radical Polymerization. Langmuir, Web Release Date: 09-Oct (2007). DOI: 10.1021/la701703c.
  25. Kavoosi M, Creagh AL, Kilburn DG, Haynes CA. Strategy for selecting and characterizing linker peptides for CBM9-tagged fusion proteins expressed in E. coli.  Biotechnol Bioeng., 98(3): 599-610 (2007).

Education

  • Ph.D. University of California at Berkeley, 1991.
  • B.Sc. University of Texas, Austin 1986.