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case western reserve university

Dennis Orthopaedics Tissue Engineering Laboratory

 
 
Principal Investigator

Tom Kean


Postdoctoral Research Associate
Department of Orthopaedics
Case Western Reserve University

Research Interests

The future of pharmaceutical treatment lies in the production of targeted delivery systems. With this in mind I am involved in several research projects which aim to target adult stem cells to pathological tissues. This work is many faceted in its development, we are investigating two methods of targeting the cells: Antibody Directed Cell Therapy and Peptide Directed Cell Therapy.

With Antibody Directed Cell Therapy we first coat the cells with palmitated protein G, this is a modified recombinant peptide that binds to the Fc region of many antibodies. This provides a general method to develop optimal coating of antibodies for attachment to many different disease or injury states. This is primarily being investigated for attachment and repair of cartilage. In collaboration with Lauren Buerkle we are investigating the lipid anchor for its efficiency of integration and the strength of the interaction once it is in the membrane.

Peptide Directed Cell Therapy is being investigated in two injury models: Ischemic heart and Ischemic limb. Phage display has produced peptides which attach to neovascular tissue. It is thought that these will be able to attach in the two injury models. These peptides have been labelled with a fluorophore and injected into the models and localisation studied by whole body and tissue sectioning.

 
CV
Education

University of Strathclyde, UK - Biochemistry & Pharmacology - The effect of hypoxia on lung endothelial nitric oxide formation - B.Sc. 2000
University of Strathclyde, UK - Pharmaceutical Analysis - Production of a general method for the detection of hydrazine in pharmaceuticals - M.Sc. 2002
University of Cardiff, UK - Development of a Synthetic uPAR Targeted Gene Delivery System - Pharmacy PhD 2006

 
Publications

1) T. Kean, M. Thanou, Invited book chapter on Chitin and Chitosan in Polymeric Biomaterials - In Press
2) T. Kean, J. H. McB. Miller, G.G. Skellern, D. Snodin, Acceptance Criteria for Levels of Hydrazine in Substances for Pharmaceutical Use and Analytical Methods for its Determination, Pharmeuropa Scientific Notes, (2006) Abstract

3) T. Kean, Development of a synthetic uPAR targeted gene delivery system (2006) PhD Thesis, Cardiff University
4) T. Kean, S. Roth, M. Thanou, Trimethylated chitosans as non-viral gene delivery vectors: Cytotoxicity and transfection efficiency. J. Control. Release, 103(3) (2005) 643-53 Abstract
5) T. Kean, S. Roth, M. Thanou, Trimethylation of chitosans: Its effect on toxicity and their application as a non-viral gene delivery system. In Journal of Pharmacy and Pharmacology, BPC Science abstracts (2004), Poster Session 2, #128 Abstract
6) T.J. Kean, C.A. Jansma, G. Borchard, M. Thanou. Targeting The uPA Receptor Using Polymer-Ligand Conjugates For Non Viral Gene Delivery. in Proc. Int. Symp. Control. Release Bioact. Mater. 2003. Glasgow, UK

 

Presentations

1) Development of a synthetic uPAR targeted gene delivery system - Invited lecture at NMP in Lecce, Italy, 2005
2) Targeted gene delivery for the treatment of cancer - at Speaking of Science, Cardiff, UK, 2005
3) Trimethylation of chitosans: Its effect on toxicity and their application as a non-viral gene delivery system - at The British Pharmaceutical Conference, Manchester, UK, 2004
4) Effect of the Degree of Chitosan Quaternisation on Cytotoxicity - at 5th International Symposium for Polymer Therapeutics, Cardiff, UK, 2005
5) Targeting Therapies to Tumours - at Speaking of Science, Cardiff, UK, 2004