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Office: (859) 257-6486
Fax: (859) 257-8994
Lab: (859) 257-8158
Email: hkohl00@uky.edu
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Heinz Kohler, MD. Ph.D.
Professor
Doctoral Studies: University of Munich.
Postdoctoral: Max Planck Institute Biochemistry Munich.
Research Statement:
Antibodies have become a major toll to fight cancers, autoimmne diseases and infections. Their development has to be credited to the Biotech Industry. Having spend several years at a successful Biotech Company, IDEC Pharmaceutical, (now Biogen-Idec) before returning to academia I have recognized the need to improve antibodies as well as a opportunity to develop novel approaches in antibody drugs that would have not been supported by Industry.
Antibodies can be improved by increases the affinity for target and by increase the target binding strength through raising the valency, i.e. the number of binding sites in one antibody molecule. I discovered several years ago a naturally occurring polyvalent antibody that increases valency by homophilic (self-binding) dimerizing binding. Working in the Markey Cancer Center we developed methods to convert therapeutic antibodies, like Herceptin and Rituxan, into homophilic antibodies with enhanced targeting and killing tumor cells. (see listed publication and link to the History of Homophilic Antibodies).
My laboratory is continuing work on homophilic therapeutic antibodies with the aim to translate our findings into the clinic.
Selected Recent Publications:
Heinz Kohler, Jean Amick, Kyle Rector, Generation of a potent recombinant homophilic chimeric anti-CD20 antibody. Hybridoma, accepted for publication PDF
Finkel, R. and Kohler, H. The Trend of amino acid gain is consistent with a doublet code. Current Proteomics, 2010, 7, 209-211
Bryan, J.A. and Kohler, H. Physical and Biological Properties of Homophilic therapeutic Antibodies, Cancer Immunology Immunotherapy, 60: 507, 2010 PDF
Heinz Kohler, Discovery of Homophilic Antibodies As Novel Drugs, Current Trends Immunology, Current Trends Immunology 10:113-118, 2009 PDF
Giuseppina C., Khallou-Laschet, J. , Vandaele, M , Gaston, Anh-Thu, Delignat,
S., Mandet, C., Kohler, H., Kaveri, S.V, and Nicoletti, A., Phosphorylcholine-targeting immunization reduces atherosclerosis. J Am Coll Cardiol 50:540,2007
Zhao, Y., Russ, M., Retter, M., Fanger, G., Morgan, C., Kohler, H., Muller, S.: Endowing Self-binding Feature Restores the Activities of a Loss-of-function Chimerized Anti-GM2 Antibody. Cancer Immunology Immunotherapy 56: 147-54. 2007 PDF
Russ, M.Lou, D. and Kohler, H. Photo-activated affinity-site cross-linking of antibodies using tryptophan containing, J Immunol Methods 304: 100-106, 2005
Heinz Kohler, AIDS Vaccines -- a continuing struggle. Int. Rev Immunol. 23: 367-368, 2004
Zhao, Y. Borwn, TL. Kohler, H. and Muller S. MTS-conjugated antiactive caspase 3 antibodies inhibit actinomycinD-induced apoptosis. Apoptosis 8: 631-637. 2003
Y. Zhao, and Heinz Kohler, Enhancing Tumor Targeting and Apoptosis Using Non-Covalent Antibody Homo-dimers, J Immunotherapy, 25:396-404, 2002
Y. Zhao, D. Lou, J. Burkett and H. Kohler. Enhanced Anti-B-cell Tumor Effects with Anti-CD20 Superantibody. J Immunotherapy, 25: 57-62, 2002.
Y. Zhao, D. Lou, J. Burkett and H. Kohler, Chemical Engineering of cell penetrating antibodies, J. Immunol Methods, 254: 137-145, 2001.
Lou D. and Kohler H. Enhanced molecular mimicry of CEA using photoaffinity crosslinked C3d peptide. Nature Biotechnology. 16:458-62.1998
Rajagopalan,K. G. Pavlinkova, S. Levy, P. Pokkuluri, M. Schiffer, B. E. Haley and H. Kohler, Novel Unconventional Binding Site in the Variable Domain of Immunoglobulins, Proc. Natl. Acad. Sci. USA .93:6019-6024. 1996
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