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.
(Applications are invited from potential graduate students with backgrounds in chemistry, biochemistry or material science for interdisciplinary graduate programs).
- PhD (Chemistry), Indian Institute of Chemical Technology. 2000
- MSc (Chemistry), Mahatma Gandhi University, India. 1994
- BSc (Chemistry), Mahatma Gandhi University, India. 1992
Awards and 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
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
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.
I. 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.
II. 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.
IV. 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.
Current projects in my lab include:
We are looking for talented graduate students and postdoctoral fellows. Please send your CV.
Since I became faculty at UBC, I have been teaching Bachelor of Medical Laboratory Sciences Students (PATH 301, 305), Medical undergraduates (PBL- FMED 402) and Chemistry undergraduates (Chem 406). I also taught 4th year undergraduate directed studies projects in Department of Pathology (PATH 438), Chemistry (CHEM 449) and Biochemistry (BIOC 548 B). In 2008, I was invited to give lectures to engineering students on blood-biomaterial interactions (MTRL 595) to provide fundamental insights into how surface properties of materials are important in the design of biomedical materials. I am also actively involved in the research supervision of graduate students, postdoctoral fellows and undergraduate students.