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
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.

Publications

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

Kalathottukaren MT, Abraham L, Kapopara PR, Benjamin FL Lai BFL, Shenoi RA, Rosell FI, Conway EM, Pryzdial ELG, Morrissey JH, Haynes CA, Kizhakkedathu JN. ( 2016) Alteration of blood clotting and lung damage by protamine are avoided using the heparin and polyphosphate inhibitor UHRA. Blood 2016 :blood-2016-10-747915; doi: https://doi.org/10.1182/blood-2016-10-747915

Yu K, Lo JC, Yan M, Yang X, Brooks DE, Hancock RE, Lange D, Kizhakkedathu JN. (2016) Anti-adhesive antimicrobial peptide coating prevents catheter associated infection in a mouse urinary infection model. Biomaterials. 2017 Feb;116:69-81.

Du C, Mendelson AA, Guan Q, Dairi G, Chafeeva I, da Roza G, Kizhakkedathu JN. (2016) Hyperbranched polyglycerol is superior to glucose for long-term preservation of peritoneal membrane in a rat model of chronic peritoneal dialysis. J Transl Med. 14(1):338.

Loy C, Meghezi S, Lévesque L, Pezzoli D, Kumra H, Reinhardt D, Kizhakkedathu JN, Mantovani D. (2016) A planar model of the vessel wall from cellularized-collagen scaffolds: focus on cell-matrix interactions in mono-, bi- and tri-culture models. Biomater Sci. 20;5(1):153-162.

Brockman KS, Kizhakkedathu JN, Santerre JP. (2016). Hemocompatibility studies on a degradable polar hydrophobic ionic polyurethane (D-PHI). Acta Biomater. 2016 Nov 3. pii: S1742-7061(16)30592-X. doi: 10.1016/j.actbio.2016.11.005.

Hamilton JL, Ul-Haq MI, Creagh AL, Haynes CA, Kizhakkedathu JN. (2016) Iron Binding and Iron Removal Efficiency of Desferrioxamine Based Polymeric Iron Chelators: Influence of Molecular Size and Chelator Density. Macromol Biosci. doi: 10.1002/mabi.201600244.

Shenoi RA, Abbina S, Kizhakkedathu JN. (2016) In Vivo Biological Evaluation of High Molecular Weight Multifunctional Acid-Degradable Polymeric Drug Carriers with Structurally Different Ketals. Biomacromolecules. 2016 17(11):3683-3693.

Li S, Constantinescu I, Guan Q, Kalathottukaren MT, Brooks DE, Nguan CY, Kizhakkedathu JN, Du C. Advantages of replacing hydroxyethyl starch in University of Wisconsin solution with hyperbranched polyglycerol for cold kidney perfusion. J Surg Res. 205(1):59-69.

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 Biomater. 40:212-25.

Hamilton JL, Imran Ul-Haq M, Abbina S, Kalathottukaren MT, Lai BF, Hatef A, Unniappan S, Kizhakkedathu JN. (2016) In vivo efficacy, toxicity and biodistribution of ultra-long circulating desferrioxamine based polymeric iron chelator. Biomaterials. 102:58-71.

Lai ZW, Weisser J, Nilse L, Costa F, Keller E, Tholen M, Kizhakkedathu JN, Biniossek M, Bronsert P, Schilling O. (2016) Formalin-Fixed, Paraffin-Embedded Tissues (FFPE) as a Robust Source for the Profiling of Native and Protease-Generated Protein Amino Termini. Mol Cell Proteomics. 15(6):2203-13.

Wen J, Weinhart M, Lai B, Kizhakkedathu JN, Brooks DE. Reversible hemostatic properties of sulfabetaine/quaternary ammonium modified hyperbranched polyglycerol. Biomaterials 86, 42-55.

Moradi S, Hadjesfandiari N, Toosi SF, Kizhakkedathu JN*, Hatzikiriakos SG*. (2016) Effect of Extreme Wettability on Platelet Adhesion on Metallic Implants: From Superhydrophilicity to Superhydrophobicity. ACS Appl Mater Interfaces. 8(27):17631-41. (*equal senior authors)

Tholen S, Wolf C, Mayer B, Knopf JD, Löffek S, Qian Y, Kizhakkedathu JN, Biniossek ML, Franzke CW, Schilling O. (2016) Skin Barrier Defects Caused by Keratinocyte-Specific Deletion of ADAM17 or EGFR Are Based on Highly Similar Proteome and Degradome Alterations. Journal of proteome research 15 (5), 1402-1417.

Leung VL, Kizhakkedathu JN. (2016) The mechanism and modulation of complement activation on polymer grafted cells. Acta biomaterialia 31, 252-263.

Koczorowska MM, Tholen S, Bucher F, Lutz L, Kizhakkedathu JN, De Wever D, Wellner UF, Biniossek ML, Stahl A, Lassmann S, Schilling O. (2016). Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations. Molecular oncology 10 (1), 40-58.

Wong NK, Misri R, Shenoi RA, Chafeeva I, Kizhakkedathu JN*, Khan MK*. (2015) Design considerations for developing hyperbranched polyglycerol nanoparticles as systemic drug carriers. Journal of Biomedical Nanotechnology J Biomed Nanotechnol. 12(5):1089-100. (*equal senior authors).

Yu K, Creagh AL, Haynes CA, Kizhakkedathu JN. (2016) Modulation of Multivalent Protein Binding on Surfaces by Glycopolymer Brush Chemistry. Macro-Glycoligands: Methods and Protocols, 183-193

Yu K, Lo JC, Mei Y, Haney EF, Siren E, Kalathottukaren MT, Hancock RE, Lange D, Kizhakkedathu JN. (2015) Toward Infection-Resistant Surfaces: Achieving High Antimicrobial Peptide Potency by Modulating the Functionality of Polymer Brush and Peptide. ACS Appl Mater Interfaces. 7(51):28591-605.

Narain R, Wang Y, Ahmed M, Lai BF, Kizhakkedathu JN. (2015). Blood Components Interactions to Ionic and Nonionic Glyconanogels. Biomacromolecules. 16(9):2990-7.

Yu K, Lai BFL, Gani J.; Mikut R, Hilpert K, Kizhakkedathu JN. (2015)Interaction of Blood Components with Natural Cathelicidins and Artificial Short Antimicrobial Peptides. Biomaterials 69, 201-211.

Schlage P, Kockmann T, Sabino F, Kizhakkedathu JN, Auf dem Keller U. (2015) Matrix Metalloproteinase 10 Degradomics in Keratinocytes and Epidermal Tissue Identifies Bioactive Substrates With Pleiotropic Functions. Mol Cell Proteomics. 14(12):3234-46.

Shenoi RA, Chafeeva I, Lai, BFL, Horte S, Kizhakkedathu JN. (2015) Bioreducible Hyperbranched Polyglycerols with Disulfide Linkages: Synthesis and Biocompatibility Evaluation. Journal of Polymer Science: Part A Polymer Chemistry 53 (18), 2104-2115.

Yang X,   Li N, Kizhakkedathu JN, Brooks DE. ( 2015) Choline Phosphate Functionalized Cellulose Membrane Developed as Potential Hemostasis Dressing Based on a Unique Bioadhesion Mechanism. International Journal of Bioscience, Biochemistry and Bioinformatics 5 (4), 211.

Schlage P, Kockmann T, Kizhakkedathu JN, auf dem Keller U. (2015) Monitoring matrix metalloproteinase activity at the epidermal-dermal interface by SILAC-iTRAQ-TAILS. Proteomics. 15 (14), 2491-2502.

Kwan D, Constantinescu I, Chapanian R, Higgins, M, Koetzler M, Samain E, Boraston AB, Kizhakkedathu, JN; Withers, S. (2015) Towards efficient enzymes for the generation of universal blood through structure-guided directed evolution. J. Am. Chem. Soc. 137 (17), 5695-5705.

Melzak KA, Yu K, Bo D, Kizhakkedathu JN*, Toca-Herrera JL* (2015). Chain Length and Grafting Density Dependent Enhancement in the Hydrolysis of Ester-Linked Polymer Brushes. Langmuir. 16; 31(23):6463-70. (*equal senior authors).

Misri R, Wong NK, Shenoi RA, Lum CM, Chafeeva I, Toth K, Rustum Y, Kizhakkedathu JN*, Khan MK*. (2015) Investigation of hydrophobically derivatized hyperbranched polyglycerol with PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics. Nanomedicine-Nanotechnology Biology and Medicine. 11 (7), 1785-1795 (*equal senior authors)

Hamilton JL, Kizhakkedathu JN. Polymeric nanocarriers for the treatment of systemic iron overload. Molecular and Cellular Therapies. 2015, 3:3DOI: 10.1186/s40591-015-0039-1.

Gao S, Guan Q, Chafeeva I, Brooks DE, Nguan CY, Kizhakkedathu JN*, Du C.* Hyperbranched polyglycerol as a colloid in cold organ preservation solutions. PLoS One. 2015 Feb 23;10(2):e0116595. (*equal senior authors)

Kumar P, Shenoi RA, Lai BF, Nguyen M, Kizhakkedathu JN,* Straus SK.*Conjugation of Aurein 2.2 to HPG Yields an Antimicrobial with Better Properties. Biomacromolecules. 2015 Mar 9;16(3):913-23 (*equal senior authors)

Godoy-Gallardo M, Mas-Moruno C, Yu K, Manero JM, Gil FJ, Kizhakkedathu JN, Rodriguez D.Antibacterial properties of hLf1-11 peptide onto titanium surfaces: a comparison study between silanization and surface initiated polymerization. 2015 Feb 9;16(2):483-96.

Sabino F, Hermes O, Egli FE, Kockmann T, Schlage P, Croizat P, Kizhakkedathu JN, Smola H, auf dem Keller U. In vivo assessment of protease dynamics in cutaneous wound healing by degradomics analysis of porcine wound exudates. Mol Cell Proteomics. 2015 Feb;14(2):354-70.

Stukas S, Robert J, Lee M, Kulic I, Carr M, Tourigny K, Fan J, Namjoshi D, Lemke K, DeValle N, Chan J, Wilson T, Wilkinson A, Chapanian R, Kizhakkedathu JN, Cirrito JR, Oda MN, Wellington CL. Intravenously injected human apolipoprotein A-I rapidly enters the central nervous system via the choroid plexus. J Am Heart Assoc. 2014 Nov 12;3(6):e001156.

Shenoi RA, Kalathottukaren MT, Travers RJ, Lai BF, Creagh AL, Lange D, Yu K, Weinhart M, Chew BH, Du C, Brooks DE, Carter CJ, Morrissey JH, Haynes CA, Kizhakkedathu JN. Affinity-based design of a synthetic universal reversal agent for heparin anticoagulants. Science Transl Med. 2014 Oct 29;6(260):260ra150

 

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

Chapanian R, Constantinescu I, Brooks DE, Scott MD, Kizhakkedathu JN. In vivo circulation, clearance, and biodistribution of polyglycerol grafted functional red blood cells. Biomaterials. 2012 Apr;33(10):3047-57.

Tholen S, Biniossek ML, Gessler AL, Müller S, Weisser J, Kizhakkedathu JN, Reinheckel T, Schilling O. Contribution of cathepsin L to secretome composition and cleavage pattern of mouse embryonic fibroblasts. Biol Chem. 2011 Nov;392(11):961-71.

Kleifeld O, Doucet A, Prudova A, auf dem Keller U, Gioia M, Kizhakkedathu JN, Overall CM. Identifying and quantifying proteolytic events and the natural N terminome by terminal amine isotopic labeling of substrates. Nat Protoc. 2011 Sep 22;6(10):1578-611.

Gao G, Yu K, Kindrachuk J, Brooks DE, Hancock RE, Kizhakkedathu JN. Antibacterial surfaces based on polymer brushes: investigation on the influence of brush properties on antimicrobial peptide immobilization and antimicrobial activity. Biomacromolecules. 2011 Oct 10;12(10):3715-27.

Tholen S, Biniossek ML, Geßler AL, Müller S, Weißer J, Kizhakkedathu JN, Reinheckel T, Schilling O. Contribution of cathepsin L to secretome composition and cleavage pattern of mouse embryonic fibroblasts. Biol Chem. 2011 Sep 8. [Epub ahead of print]

Beaudette P, Rossi NA, Huesgen PF, Yu X, Shenoi RA, Doucet A, Overall CM, Kizhakkedathu JN. Development of soluble ester-linked aldehyde polymers for proteomics. Anal Chem. 2011 Sep 1;83(17):6500-10. Epub 2011 Aug 11.

Doucet A, Kleifeld O, Kizhakkedathu JN, Overall CM. Identification of proteolytic products and natural protein N-termini by Terminal Amine Isotopic Labeling of Substrates (TAILS). Methods Mol Biol. 2011;753:273-87.

Zou Y, Lam A, Brooks DE, Phani AS, Kizhakkedathu JN. Bending and stretching actuation of soft materials through surface-initiated polymerization. Angew Chem Int Ed Engl. 2011 May 23;50(22):5116-9.

Gao G, Lange D, Hilpert K, Kindrachuk J, Zou Y, Cheng JT, Kazemzadeh-Narbat M, Yu K, Wang R, Straus SK, Brooks DE, Chew BH, Hancock RE, Kizhakkedathu JN. The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides. Biomaterials. 2011 Jun;32(16):3899-909.

Ye L, Letchford K, Heller M, Liggins R, Guan D, Kizhakkedathu JN, Brooks DE, Jackson JK, Burt HM. Synthesis and characterization of carboxylic acid conjugated, hydrophobically derivatized, hyperbranched polyglycerols as nanoparticulate drug carriers for cisplatin. Biomacromolecules. 2011 Jan 10;12(1):145-55.

Zou Y, Lai BF, Kizhakkedathu JN, Brooks DE. Inhibitory effect of hydrophilic polymer brushes on surface-induced platelet activation and adhesion. Macromol Biosci. 2010 Dec 8;10(12):1432-43.

Kizhakkedathu JN, Creagh AL, Shenoi RA, Rossi NA, Brooks DE, Chan T, Lam J, Dandepally SR, Haynes CA. High molecular weight polyglycerol-based multivalent mannose conjugates. Biomacromolecules. 2010 Oct 11;11(10):2567-75.

Lai BF, Creagh AL, Janzen J, Haynes CA, Brooks DE, Kizhakkedathu JN. The induction of thrombus generation on nanostructured neutral polymer brush surfaces. Biomaterials. 2010 Sep;31(26):6710-8.

Lai BF, Zou Y, Brooks DE, Kizhakkedathu JN. The influence of poly-N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide on fibrin polymerization, cross-linking and clot structure. Biomaterials. 2010 Aug;31(22):5749-58.

Yu K, Kizhakkedathu JN. Synthesis of Functional Polymer Brushes Containing Carbohydrate Residues in the Pyranose Form and Their Specific and Nonspecific Interactions with Proteins. Biomacromolecules. 2010 Oct 18.

Melzak, K.A., Moreno-Flores, A, Yu, K, Kizhakkedathu, J.N. , Toca-Herrera, J. Rationalized approach to the determination of contact point in force-distance curves: Application to polymer brushes in salt solutions and in water. Microscopy Research and Technique 2010 Oct;73(10):959-64.

Kleifeld O, Doucet A, auf dem Keller U, Prudova A, Schilling O, Kainthan RK, Starr AE, Foster LJ, Kizhakkedathu JN, Overall CM. Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products. Nat Biotechnol. 2010 Mar;28(3):281-8. Epub

Rossi, Nicholas, A.A.; Constantinescu, Iren; Brooks, Donald; Scott, Mark; Kizhakkedathu, Jayachandran (2010) Enhanced Cell Surface Polymer Grafting in Concentrated and Non-Reactive Aqueous Polymer Solutions. Journal of the American Chemical Society 132, 3423-3430

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