Jayachandran Kizhakkedathu

Contact Information
Life Sciences Centre
#4408 – 2350 Health Sciences Mall
Vancouver, BC
Canada V6T 1Z3
Tel: 1-604-822-7085
Fax: 1-604-822-7742
Email: jay@pathology.ubc.ca
Lab Website: http://pathology.ubc.ca/faculty/jayachandran-kizhakkedathu/

Current Positions

  • Professor, Pathology and Laboratory Medicine, Medicine.
  • Michael Smith Foundation for Health Research Scholar.
  • Associate Member, Department of Chemistry.

Research Interests

  • Macromolecular Therapeutics:
    A) High molecular weight Iron chelators for Chelation therapy: Fundamental studies are directed towards the development of blood compatible Iron chelating polymers which could bind Iron inside the human body and excrete it through kidney. Applications include the development of treatments to secondary iron overload, a condition caused by severe blood transfusion (e.g. sickle-cell anaemia, beta-thalessimia). This is particularly important due to the fact that humans do not have an iron excretion pathway.

    B)
     Polymeric Antidotes to reverse the clotting effects of anticoagulants: Anticoagulation is one of the commonly used clinical interventions in modern medicine. Heparin based anticoagulants are widely used. We are developing a safe and effective antidote which works effectively against unfractionated heparin, low molecular weight heparins, and fondaparinux and other anticoagulants.

    C)
     Glyco-conjugates as inhibitors of cell or protein interactions or immuno-targeting agents: The importance of carbohydrate-protein/cell binding in various biological events makes them very attractive in the development of therapeutic agents specifically targeting certain proteins or cells. But the weak affinity of monovalent carbohydrate ligands to proteins and cell receptors hindered the development of carbohydrate-based therapeutic agents. Our interests are in the development of blood compatible multivalent polymer glyco-conjugates and surfaces for cell targeting purposes
  • Polymer Cell Derivatization Technology (Universal blood donor cells and Cell based therapeutic carriers):
    Our focus is on the development of polymeric cell derivatization technology for the creation of universal blood donor cells. We are developing novel polymers and polymerization techniques to couple polymers on to erythrocytes towards this purpose. We are also extending the application of this technology for converting red cells as a carrier for homeostatic and antithrombotic drugs.
  • Development of Blood Compatible Surface Coatings: 
    Our lab is interested in the development of anti-thrombotic polymeric coating for implants. Our goal is to understand the various processes when blood comes in contact with a polymeric surface using various blood interaction analysis and proteomic methods. Novel polymer derivatization techniques being developed to manipulate its surface interaction with blood and other biological fluids. On a fundamental level, we investigate the blood- surface interaction using well-defined and well-characterized surfaces using a variety of surface analytical techniques, calorimetry, proteomics and blood interaction studies. Major interests are in the development of specialty surface coatings for various implants (orthopaedic, coronary stents), storage containers for blood and bio-sensors.
  • Development of Polymeric Reagents for Proteomic Applications:
    Proteomics relies upon high efficiency mass spectrometry (MS) analysis of tryptic peptides of up to thousands of proteins present in biological compartments. MS based functional proteomics has emerged as a powerful tool in quantifying and analyzing proteome modifications submitted to different treatments. However, the complexity and high dynamic range of proteins in living organisms and the fact that interesting proteins/protein modifications are often found in low abundance jeopardize functional proteomic analysis. We are developing highly functional, soluble polymeric supports which can be used for selective enrichment of peptides before MS analysis.

Selected Publications

Full list of publications (http://scholar.google.ca/citations?user=zL7GeOwAAAAJ&hl=en)

  1. Marshall, NC.; Klein, T; Thejoe, M; von Krosigk, N; Kizhakkedathu, J; Finlay, BB; Overall, CM. (2018). Global profiling of proteolysis from the mitochondrial amino terminome during early intrinsic apoptosis prior to caspase-3 activation. Journal of Proteome Research. Accepted.
  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. Meneksedag-Erol, D.; Kizhakkedathu JN.; Tang, T., Uludăg,H. (2018). Molecular Dynamics Simulations on Nucleic Acid Binding Polymers Designed To Arrest Thrombosis. ACS Applied Materials & Interfaces. 10: 28399-28411.
  4. Kumar,P*.; Pletzer, D.; Haney, EF.; Rahanjam, N.; Cheng, JTJ.; Yue, M.; Aljehani, W.; Hancock,REW.; Kizhakkedathu, JN.; Straus, SK. (2018). Aurein-derived antimicrobial peptides formulated with pegylated phospholipid micelles to target methicillin-resistant Staphylococcus aureus skin infections. ACS Infectious Diseases.
  5. Narges Hadjesfandiari*, Marie Weinhart*, Jayachandran N. Kizhakkedathu, Rainer Haag, Donald E. Brooks. (2018). Development of an antifouling coating for platelet storage bags using mussel-inspired chemistry. Advanced Health Care Materials. 7:1700839.
  6. Kumar P*, Kizhakkedathu JN#, Straus SK#. (# equal corresponding author). (2018). Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo.Biomolecules. 8: pii: E4.
  7. Sabino F, Egli FE, Savickas S, Holstein J, Kaspar D, Rollmann M, Kizhakkedathu JN, Pohlemann T, Smola H, Auf dem Keller U. (2018). Comparative Degradomics of Porcine and Human Wound Exudates Unravels Biomarker Candidates for Assessment of Wound Healing Progression in Trauma Patients. J Invest Dermatol.138: 413-422.
  8. Späth, MR.;Bartram, MP.; Palacio-Escat, N.;Hoyer, KJR.;Debes, C.;Demir, F.;Schroeter, CB.; Mandel, AM.;Grundmann, F.;Ciarimboli, G.; Beyer, A.; Kizhakkedathu, JN.; Brodesser, S.;Göbel, H.; Becker, JU.;Benzing, T.;Schermer, B.; Höhne, M.; Burst, V.;Saez-Rodriguez, J.; Huesgen, PF.; Müller, R.; Rinschen, MM. (2018). The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury. Kidney International. In Press.
  9. Mei, Y*.; Yu, K*.; Lo, J.; Hadjesfandiari, N*.; Ahmadabadi, HY*.; Brooks, DE.; Lange, D.; Kizhakkedathu, JN. (2018). Polymer-Nanoparticle Interaction as a Design Principle in the Development of a Durable Ultra- thin Universal Binary Anti-Biofilm Coating with Long-Term Activity. ACS Nano. Published.
  10. 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.
  11. Siren EMJ, Chapanian R, Constantinescu I, Brooks DE, Kizhakkedathu J. (2018). Oncotically Driven Control over Glycocalyx Dimension for Cell Surface Engineering and Protein Binding in the Longitudinal Direction. Scientific Reports. 8: 7581.
  12. Julienne Jagdeo, Antoine Dufour, Theo Klein, Nestor Solis, Oded Kleifeld, Jayachandran Kizhakkedathu, Honglin Luo, Christopher Overall, and Eric Jan. (2018). N-Terminomics TAILS identifies host cell substrates of poliovirus and coxsackievirus B3 3C proteinases that modulate virus infection. Journal of Virology. 92(8): pii: e02211-17.
  13. Han B, Guan Q, Chafeeva I, Mendelson AA, Roza GD, Liggins R, Kizhakkedathu JN, Du C. (2018). Peritoneal and Systemic Responses of Obese Type II Diabetic Rats to Chronic Exposure to a Hyperbranched Polyglycerol-based Dialysis Solution. Basic Clin Pharmacol Toxicol. In Press.
  14. 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.
  15. Kumar, P*; Takayesu, A*; Abbasi, U*; Kalathottukaren, MT*; Abbina, S*; Kizhakkedathu, JN#; Straus, SK# (# equal senior authors). (2017). Antimicrobial peptide-polymer conjugates with high activity: Influence of polymer molecular weight and peptide sequence on antimicrobial activity, proteolysis and biocompatibility. ACS Applied Materials & Interfaces. 9(43): 37575-37586.
  16. Wong NKY, Shenoi RA*, Abbina S*, Chafeeva I, Kizhakkedathu JN, Khan MK. (2017). Non-transformed and Cancer Cells Utilize Different Endocytic Pathways to Internalize Hyperbranched Polyglycerol Nanoparticle Variants: Implications on Nanocarrier Design. Biomacromolecules. 18(8): 2427-2438.
  17. Brockman KS*, Kizhakkedathu JN, Paul Santerre J. (2017). Hemocompatibility Studies on a Degradable Polar Hydrophobic Ionic Polyurethane (D-PHI). Acta Biomaterialia. 48: 368-377.
  18. 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.
  19. Rinschen MM, Hoppe A, Völker LA, Schurke E, Höhne M, Malisec M, Kurschat C, Kizhakkedathu JN, Schermer B, Huesgen P, Benzing T. (2017). N-Degradomic analysis reveals a proteolytic network processing the podocyte cytoskeleton. Journal of the American Society of Nephrology. XX: XX. In Press.
  20. Abbina, S*; Vappala, S*; Kumar, P*; Siren, EMJ*.; La, CC.*; Abbasi, U.*; Brooks, DE.; Kizhakkedathu, JN. (2017). Hyperbranched Polyglycerols: Recent Advances in Synthesis, Biocompatibility and Biomedical Applications. Journal of Materials Chemistry B: Materials for Biology and Medicine. 5(47): 9249-9277.
  21. Li S, Liu B, Guan Q, Chafeeva I*, Brooks DE, Nguan CY, Kizhakkedathu JN, Du C. (2017). Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats. Am J Transl Res. 9(2): 429-441.
  22. Yu K*, Lo JC, Yan M*, Yang X, Brooks DE, Hancock RE, Lange D, Kizhakkedathu JN. (2017). Anti- adhesive antimicrobial peptide coating prevents catheter associated infection in a mouse urinary infection model. Biomaterials. 116: 69-81.
  23. Brousseau-Nault M, Kizhakkedathu JN, Kim H. (2017). Chronic periodontitis is associated with platelet factor 4 (PF4) secretion: a pilot study. J Clin Periodontol. 44(11): 1101-1111.
  24. 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.
  25. Kotsuchibashi, Y; Lee, CM; Constantinescu, I; Takeuchi, LE. *; Vappala, S*; Kizhakkedathu, JN.; Narain, R; Ebara, M; Aoyagi, T. (2017). A nanoparticle-preparation kit using ethylene glycol-based block copolymers with a common temperature-responsive block. Polymer Chemistry. 8(47): 7311-7315.
  26. Brockman KS*, Lai BFL*, Kizhakkedathu JN, Santerre JP. (2017). Hemocompatibility of Degrading Polymeric Biomaterials: Degradable Polar Hydrophobic Ionic Polyurethane versus Poly(lactic-co-glycolic) Acid. Biomacromolecules. 18(8): 2296.
  27. 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.
  28. Yang X, Li N, Constantinesco I, Yu K, Kizhakkedathu JN, Brooks DE. (2016). Choline phosphate functionalized cellulose membrane: A potential hemostatic dressing based on a unique bioadhesion mechanism.Acta Biomaterialia. 40: 212-25.
  29. Yang X, Li N, Constantinesco I, Yu K, Kizhakkedathu JN, Brooks DE. (2016). Choline phosphate functionalized cellulose membrane: A potential hemostatic dressing based on a unique bioadhesion mechanism.Acta Biomaterialia. 40: 212-25.

Education

  • Ph.D. (Chemistry), Indian Institute of Chemical Technology, 2000.
  • M.Sc. (Chemistry), Mahatma Gandhi University, India, 1994.
  • B.Sc. (Chemistry), Mahatma Gandhi University, India, 1992.