Research Summary

Our research program at the Centre for Blood Research, University of British Columbia is based on tailoring the molecular level interactions of synthetic polymers with biological systems to design novel biomaterials in a translational setting. We take an integrative, interdisciplinary approach with an understanding of the pathophysiology of diseases and advanced polymer synthesis in combination with well-designed biological assays and animal models towards the discovery of novel polymers as therapeutics, and technologies for biomedical and clinical use. Primarily my lab engages in four independent, yet closely related research themes:

Macromolecular Therapeutics
Cell-Surface Engineering
Proteomic Reagents
Blood-Compatible Surfaces and Devices

Major research projects include i) the development of synthetic polymers as bioactive pharmaceuticals for unmet clinical needs in iron chelation therapy and anticoagulation therapy, ii) the development of novel methods for the prevention of immunological rejection of donor cells, tissues/organs, iii) polymer based proteomic reagents for the analysis of blood proteome, iv) the development of biocompatible and antimicrobial coatings for biomedical devices and implants.

Intellectual Property

Patents

ANTITHROMBOTIC COMPOUNDS.. Canada. 62004866. 2014-05-29.

POLYMER-BASED DIALYSATE. United States. US Provisional Application (UBC Ref. No.: 12-065D). 2012-04-24.

SHAPE MEMORY MATERIALS BY SURFACE MODIFICATION. United States. PCT/CA2012/050060. 2012-02-03.

Polyacetal or polyketal and ether polymers, their conjugates, and therapeutic use. United States. WO
2011140644. 2011-11-17.

Polymers for Reversing Heparin-Based Anticoagulation. United States. PCT/CA2011/050603. 2011-09-28.

Derivatized hyperbranched polyglycerols. United States. WO 2011106877. 2011-09-09.

SYNTHETIC PLATELETS. Canada. CA 2599849. 2008-08-12.

Polymers containing zwitterionic endgroups. United States. WO 2008074154. 2008-06-26.

Surface cross-linked lipidic particles, methods of production for controlled drug delivery. Canada. EP
1897536. 2008-03-12.

Polymer chelation structure for binding metal and/or heme in a mammal. United States. US
20070274945. 2007-11-27.

POLYMER-BASED SERUM ALBUMIN SUBSTITUTE. United States. WO 2006130978. 2006-12-14.

Licenses

Polymers for Reversing Heparin-Based Anticoagulation

SHAPE MEMORY MATERIALS BY SURFACE MODIFICATION

Disclosures

Khan, M; Kizhakkedathu, JN; Misri, R; Nelson, W.; Shenoi, R.; Brooks, DE. Nanoparticulate Delivery
systems for Cancer. An invention disclosure has been filled to UBC in November 2013.
Disclosed. Filing Date: 2013-12-17

Polymer based organ and tissue preservation solution
Disclosed. Filing Date: 2012-08-08

Antimicrobial and antithrombotic surface coatings based surface grafted copolymer brushes.
Disclosed. Filing Date: 2009-08-05

High Affinity Glyconjugates Based on Hyperbranched Polyglycerol.
Disclosed. Filing Date: 2008-08-08

Bio

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

Teaching

UBC Student/Postdoctoral Supervision

Principal Supervisor Erika Siren, Doctorate (In Progress)
Student Degree Start Date: 2014/1
Project Description: Investigation of role of cell surface coating on the prevention of
ischemic-perfusion injury

Principal Supervisor Yan Mei, Doctorate (In Progress)
Student Degree Start Date: 2012/9

Principal Supervisor Kumar, Prashant, Doctorate (In Progress)
Student Degree Start Date: 2011/9

Principal Supervisor Leung, Vincent, Master’s Thesis (In Progress)
Student Degree Start Date: 2011/9

Principal Supervisor Kalathottukaren, Manu Thomas, Doctorate (In Progress)
Student Degree Start Date: 2011/1

Co-Supervisor Hadjesfandiari, Narges, Doctorate (In Progress)
Student Degree Start Date: 2010/9

Principal Supervisor Chapanian, Rafi, Post-doctorate (In Progress)
Student Degree Start Date: 2010/2

Principal Supervisor Imran Ul-Haq, M, Post-doctorate (Completed)
Student Degree Start Date: 2010/1
Student Degree Received Date: 2012/12

Co-Supervisor Alizadeh, Mahsa, Doctorate (In Progress)
Student Degree Start Date: 2010/1

Principal Supervisor Bajgai, Madhab, Post-doctorate (In Progress)
Student Degree Start Date: 2009/10

Principal Supervisor Hamilton, Jasmine, Doctorate (In Progress)
Student Degree Start Date: 2009/9

Principal Supervisor Shenoi, Rajesh A, Post-doctorate (In Progress)
Student Degree Start Date: 2008/11

Principal Supervisor Yu, Kai, Post-doctorate (In Progress)
Student Degree Start Date: 2008/3

Co-Supervisor Yu, Xifei, Post-doctorate (Completed)
Student Degree Start Date: 2008/2
Student Degree Received Date: 2013/6

Principal Supervisor Guangzheng Gao,, Post-doctorate (Completed)
Student Degree Start Date: 2008/1
Student Degree Received Date: 2010/8

Co-Supervisor Vijaya Lakshmi,, Post-doctorate (Completed)
Student Degree Start Date: 2007/2
Student Degree Received Date: 2008/1
Project Description: Binding studies of synthetic albumin substitute

Principal Supervisor Yuquan Zou, Post-doctorate (Completed)
Student Degree Start Date: 2006/10
Student Degree Received Date: 2010/8

Principal Supervisor Jian Song,, Doctorate (In Progress)
Student Degree Start Date: 2006/10

Principal Supervisor Nicholas AA Rossi,, Post-doctorate (Completed)
Student Degree Start Date: 2006/9
Student Degree Received Date: 2010/2

Principal Supervisor Patrick Beaudette,, Master’s Thesis (Completed)
Student Degree Start Date: 2006/9
Student Degree Received Date: 2009/9

Principal Supervisor Benjamin Lai,, Master’s Thesis (Completed)
Student Degree Start Date: 2006/9
Student Degree Received Date: 2009/9

Principal Supervisor Reddy Dendapally Srinivas, Post-doctorate (Completed) , Purdue University
Student Degree Start Date: 2005/7
Student Degree Received Date: 2006/7

Co-Supervisor Ranganathan Krishnan, Post-doctorate (Completed)
Student Degree Start Date: 2004/9
Student Degree Received Date: 2006/12

Co-Supervisor Coad Bryan,, Doctorate (Completed)
Student Degree Start Date: 2002/1
Student Degree Received Date: 2006/8
Project Description: New Chromatographic media for native state protein seperation

Awards

UBC Award for Excellence in Basic Science Research, 2013
Career Investigator Award, Michael Smith Foundation for Health Research, July 2011 – June 2019
Excellence in Research and Discovery, UBC Department of Pathology, 2011
New Investigator Award in Transfusion Science, Canadian Institute of Health Research, March 2005 – February 2010

Publications

 
Comprehensive List
Google Scholar

Selected Publications

  1. Shenoi RA, Kalathottukaren MT, Travers, RJ, Lai BFL, Creagh AL, Lange D, Yu K, Weinhart M, Chew B, Du C, Brooks DE, Carter CJ, Morrissey JH, Haynes CA and Kizhakkedathu JN.* Affinity-based Design and Discovery of a Synthetic Universal Reversal Agent for Clinically Used Parenteral Heparin Anticoagulants. Science Transl. Med., In Press.
  2. Hamilton, JL.; Hatef, A.; Imran ul-haq, M.; Nair, N.; Unniappan, S.*; Kizhakkedathu, JN.* (2014) Clinically Approved Iron Chelators Influence Zebrafish Mortality, Hatching Morphology and Cardiac Function. PLOS ONE (in press) (DOI: 10.1371/journal.pone.0109880).
  3. Travers, RJ.; Shenoi, RA.; Kalathottukaren, MT.; Kizhakkedathu, JN.; and Morrissey, JH. (2014) Nontoxic polyphosphate inhibitors reduce thrombosis while sparing hemostasis. Blood (online) In press.
  4. Yu, K.; Lai, BFL.; Krisinger, MJ.; Conway, EM.; Kizhakkedathu, JN.* (2014) Modulation of Complement Activation and Amplification on Nanoparticle Surfaces by Glycopolymer Conformation and Chemistry. ACS Nano 8(8):7687-703.
  5. Yu, K; Mei, Y; Hadjesfandiari, N; Kizhakkedathu, JN.* (2014) Engineering Biomaterials Surfaces to Modulate the Host Response. Colloids and Surfaces B: Biointerfaces. (published online) (invited review)
  6. Chapanian, R., Kwan, DH, Constantinescu, I., Shaikh, F., Rossi, NAA., Withers, SG*. and Kizhakkedathu, JN* (2014) “Enhancement of biological reactions on cell surface via Macromolecular Crowding.” Nature Communications 5:4683
  7. Imran ul-haq, M; Lai, Benjamin F. L.; Kizhakkedathu, JN.* (2014) Hybrid Polyglycerols with Long Blood Circulation: Synthesis, Biocompatibility, and Biodistribution. Macromolecular Bioscience (2014), Ahead of Print.
  8. Hadjesfandiari, N; Yu, K; Mei, Y; Kizhakkedathu, JN.* (2014) Polymer brush-based approaches for the development of infection-resistant surfaces. Journal of Materials Chemistry B: Materials for Biology and Medicine 2(31), 4968-4978. (Invited Highlights for the Journal)
  9. Du, Caigan; Mendelson, Asher A.; Guan, Qiunong; Chapanian, Rafi; Chafeeva, Irina; da Roza, Gerald; Kizhakkedathu, JN.* (2014) The size-dependent efficacy and biocompatibility of hyperbranched polyglycerol in peritoneal dialysis. Biomaterials 35(5), 1378-1389.
  10. Lai, B. F. L.; Zou, Yuquan; Yang, X; Yu, X; Kizhakkedathu, JN.* (2014) Abnormal blood clot formation induced by temperature responsive polymers by altered fibrin polymerization and platelet binding. Biomaterials 35(8), 2518-2528.
  11. Schlage P, Egli FE, Nanni P, Wang LW, Kizhakkedathu JN, Apte SS, Auf dem Keller U. (2014)Time-resolved analysis of the matrix metalloproteinase 10 substrate degradome. Mol Cell Proteomics. 13(2):580-93.
  12. Yu, X; Yang, X; Horte, S; Kizhakkedathu, JN.; Brooks, DE. (2014) A Thermoreversible Poly(Choline Phosphate) Based Universal Biomembrane Adhesive. Macromolecular Bioscience 14(3):334-9.
  13. Tholen, S.; Biniossek, ML.; Gansz, M.; Ahrens, TD.; Schlimpert, M.; Kizhakkedathu, JN.; Reinheckel, T; Schilling, O. (2014) Double deficiency of cathepsins B and L results in massive secretome alterations and suggests a degradative cathepsin-MMP axis. Cellular and Molecular Life Sciences 71(5):899-916.
  14. Shahinian, H; Loessner, D; Biniossek, ML.; Kizhakkedathu, JN.; Clements, JA.; Magdolen, V; Schilling, O (2014). Secretome and degradome profiling shows that Kallikrein-related peptidases 4, 5, 6, and 7 induce TGFβ-1 signaling in ovarian cancer cells. Molecular Oncology 8(1):68-82.
  15. Yu, X; Yang, X; Horte, S; Kizhakkedathu, JN.; Brooks, DE. (2014) A pH and thermosensitive choline phosphate-based delivery platform targeted to the acidic tumor microenvironment. Biomaterials 35(1), 278-286.
  16. Imran ul-haq, M.; Hamilton, JL.; Lai, BFL.; Shenoi, RA.; Horte, S.; Constantinescu, I.; Leitch, HA.; Kizhakkedathu, JN*. (2013) A Long Acting Dendritic Polymer Based Nanomedicine with Reduced Toxicity and Enhanced Iron Chelation Efficiency for the Treatment of Iron Overload Disorders. ACS Nano 7(12), 10704-10716.
  17. Yu, K; Creagh, A.; Haynes, CA.; Kizhakkedathu, JN.* (2013) Lectin Interactions on Surface-Grafted Glycostructures: Influence of the Spatial Distribution of Carbohydrates on the Binding Kinetics and Rupture Forces. Analytical Chemistry 85(16), 7786-7793.
  18. Yu X, Zou Y, Horte S, Janzen J, Kizhakkedathu JN, Brooks DE. Thermal reversal of polyvalent choline phosphate, a multivalent universal biomembrane adhesive. Biomacromolecules. 2013 Aug 12;14(8):2611-21
  19. Chapanian R, Constantinescu I, Medvedev N, Scott MD, Brooks DE, Kizhakkedathu JN. Therapeutic cells via functional modification: influence of molecular properties of polymer grafts on in vivo circulation, clearance, immunogenicity, and antigen protection. Biomacromolecules. 2013 Jun 10;14(6):2052-62.
  20. Shenoi RA, Lai BF, Imran ul-haq M, Brooks DE, Kizhakkedathu JN. Biodegradable polyglycerols with randomly distributed ketal groups as multi-functional drug delivery systems. Biomaterials. 2013 Aug;34(25):6068-81.
  21. Yu X, Yang X, Horte S, Kizhakkedathu JN, Brooks DE. ATRP synthesis of poly(2-(methacryloyloxy)ethyl choline phosphate): a multivalent universal biomembrane adhesive. Chem Commun (Camb). 2013 Aug 7;49(61):6831-3.
  22. Chapanian R, Constantinescu I, Brooks DE, Scott MD, Kizhakkedathu J. Antigens protected functional red blood cells by the membrane grafting of compact hyperbranched polyglycerols. J Vis Exp. 2013 Jan 2;(71).
  23. Chapanian R, Constantinescu I, Rossi NA, Medvedev N, Brooks DE, Scott MD, Kizhakkedathu JN. Influence of polymer architecture on antigens camouflage, CD47 protection and complement mediated lysis of surface grafted red blood cells. Biomaterials. 2012 Nov;33(31):7871-83.
  24. Yu X, Liu Z, Janzen J, Chafeeva I, Horte S, Chen W, Kainthan RK, Kizhakkedathu JN, Brooks DE. Polyvalent choline phosphate as a universal biomembrane adhesive. Nat Mater. 2012 Mar 18;11(5):468-76.
  25. 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.
  26. Yu K, Lai BF, Kizhakkedathu JN. Carbohydrate structure dependent hemocompatibility of biomimetic functional polymer brushes on surfaces. Adv Healthc Mater. 2012 Mar;1(2):199-213.
  27. Imran ul-haq M, Lai BF, Chapanian R, Kizhakkedathu JN. Influence of architecture of high molecular weight linear and branched polyglycerols on their biocompatibility and biodistribution. Biomaterials. 2012 Dec;33(35):9135-47.
  28. Shenoi RA, Lai BF, Kizhakkedathu JN. Synthesis, characterization, and biocompatibility of biodegradable hyperbranched polyglycerols from acid-cleavable ketal group functionalized initiators. Biomacromolecules. 2012 Oct 8;13(10):3018-30.
  29. Shenoi RA, Narayanannair JK, Hamilton JL, Lai BF, Horte S, Kainthan RK, Varghese JP, Rajeev KG, Manoharan M, Kizhakkedathu JN. Branched multifunctional polyether polyketals: variation of ketal group structure enables unprecedented control over polymer degradation in solution and within cells. J Am Chem Soc. 2012 Sep 12;134(36):14945-57.
  30. Chapanian R, Constantinescu I, Rossi NA, Medvedev N, Brooks DE, Scott MD, Kizhakkedathu JN. Influence of polymer architecture on antigens camouflage, CD47 protection and complement mediated lysis of surface grafted red blood cells. Biomaterials. 2012 Nov;33(31):7871-83.
  31. Ahmed M, Lai BF, Kizhakkedathu JN, Narain R. Hyperbranched Glycopolymers for Blood Biocompatibility. Bioconjug Chem. 2012 Apr 24.Yu, X; Liu, Z; Janzen, J; Chafeeva, I; Horte, S; Chen, W; Kainthan, R K.; Kizhakkedathu, J. N.*; Brooks, D E* (2012) . Polyvalent choline phosphate as a universal biomembrane adhesive. Nature Materials 11(5), 468-476. (* equal senior authors)
  32. Ahmed, M; Lai, B.F.L.; Kizhakkedathu, J. N.; Narain, R (2012) Hyperbranched Glycopolymers for Blood Biocompatibility. Bioconjugate Chemistry (published online)
  33. 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.
  34. Gao, G; Cheng, JTG, Hancock, REW, Straus, S, Kizhakkedathu, JN (2012) Biomembrane Interactions of Polymer Brush and Soluble Polymer Tethered Host Defence IDR-1010: Insight into the Mechanism of Action of Surface Immobilized Peptides. Chemistry and Biology 19, 199-209.
  35. Yu, K, Lai, BF, Kizhekkedathu, JN (2012) Carbohydrate Structure Dependent Hemocompatibility of Biomimetic Functional Polymer Brushes on Surfaces. Advanced Healthcare Materials 1, 199-213.
  36. 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.
  37. 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.
  38. Beaudette P, Rossi NA, Huesgen PF, Yu X, Shenoi RA, Doucet A, Overall CM, Kizhakkedathu JN (2011) Development of soluble ester-linked aldehyde polymers for proteomics. Anal Chem. 83(17):6500-10.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. 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.
  47. 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.