Academic Rank:
Associate Professor, UBC
Associate Member, Dept of Chemistry, UBC
Affiliation(s):
Centre for Blood Research
Location:
Centre for Blood Research, Life Sciences Centre

Short Bio:

My laboratory at Centre for Blood Research (www.cbr.ubc.ca) has interests in various aspects of biomaterial research for applications involving blood and polymers.

My research focuses on:

  1. Macromolecular Therapeutics
    • High molecular weight Iron chelators for Chelation therapy
    • Polymeric Antidotes to reverse the clotting effects of anticoagulants
  2. Polymer Cell Derivatization Technology (Universal blood donor cells and Cell based therapeutic carriers
  3. Development of Blood Compatible Surface Coatings
  4. Development of Polymeric Reagents for Proteomic Applications
Academic Backgrounds:
  • PhD (Chemistry), Indian Institute of Chemical Technology. 2000
  • MSc (Chemistry), Mahatma Gandhi University, India. 1994
  • BSc (Chemistry), Mahatma Gandhi University, India. 1992
Awards & Recognition:
  • UBC Faculty of Medicine ‘ Distinguished Achievement Award’. 2013
  • MSFHR Career Scholar. 2011
  • Department of Pathology and Laboratory Medicine ‘Excellence in Research and Discovery Award’. 2011
  • CIHR New Investigator. 2005
Selected Publications
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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)
    (IF-6.504; Citations: ).
  • 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.
  • 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.
Current Projects in My Lab Include:

We are looking for talented graduate students and postdoctoral fellows. Please send your CV.

Research:

Major thrust of my research program is to understand molecular level interactions of tailored synthetic polymers with biological systems in the design of novel biomaterials. We take an integrative and interdisciplinary approach with an understanding of the pathophysiology of diseases: advanced polymer synthesis in combination with well designed biological assays and animal models for the discovery of novel polymers and technologies to address unmet clinical needs.

  1. MACROMOLECULAR THERAPEUTICS:
  • A) Modular Design of  Macromolecular  Iron sequesters: Fundamental studies are directed towards the development of blood compatible long acting Iron chelators which could bind Iron inside the human body and excrete it through kidney. It is estimated that 300,000 babies are born annually with severely low amounts of normal red blood cells (anemia) and many of them require repeated blood transfusions. Unfortunately the blood transfusion will result the build-up of toxic iron in the body. This innovative approach will lead to long circulating and non-toxic iron chelators for the treatment for transfusion associated iron overload (e.g. sickle-cell anaemia, beta-thalessimia, myelodysplastic syndromes) and cancer.
  • B) Antidotes for Anticoagulants to Address Bleeding Complications: Anticoagulation is one of the commonly used clinical interventions in modern medicine.  Parenteral anticoagulants, namely unfractionated heparins (UFH), low molecular weight heparins (LWMHs) and the synthetic heparin pentasaccharide, fondaparinux, are used universally for the prevention of blood coagulation in surgical procedures and and have vital roles in the prophylaxis, and treatment of cardiovascular diseases such as venous and arterial thromboembolism. We are developing novel polymeric systems which reverse the activity of all heparin based anticoagulants.
  1. 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 and cell surface binding polymers. We are developing novel polymers and techniques to conjugate polymers on to erythrocytes and other cells towards this purpose. We are also extending the application of this technology for converting red cells as a carrier for homeostatic and antithrombotic drugs.

III. DEVELOPMENT OF ANTITHROMBOTIC AND ANTIMICROBIAL SURFACES:

Over the years, we have been working on the development of surface modification methods for various surfaces for enhancing biocompatibility.  Our goal is to understand the various processes when blood comes in contact with a polymeric surface using using a variety of surface analytical techniques, calorimetry, proteomics, blood interaction studies, antibacterial assays and cell-adhesion studies. Novel polymer modification techniques being developed to manipulate its surface interaction with blood, other biological fluids, bacteria and cells. Major interests are in the development of specialty surface coatings for various implants (orthopedic, coronary stents), storage containers for blood and bio-sensors and antimicrobial coatings for implants.

  1. 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.