|Title:||Professor, Biochemistry, Biophysics|
|Phone:||(773) 508-3121 or (773) 508-3100|
B.S. with honors, 1967, Iowa State University
Ph.D., 1972, Duke University
American Cancer Society Post-Doctoral Fellow, 1972-1975, Purdue University
Visiting Scholar, 1992, Harvard University; 2003, Northwestern University; 2006, University of Illinois at Urbana-Champaign
Our research focuses on three exciting areas of protein science. The first is the development of polymeric hemoglobins as potential blood substitutes. The second is to develop cancer-targeted photodynamic therapy agents. The third focus is to understand protein-ligand interactions through molecular dynamics simulations.
We are synthesizing polymers of hemoglobin that include antioxidant enzymes (catalase and superoxide dismutase) to be used as blood substitutes. The syntheses depend on complimentary sulfhydryl - maleimide chemistry to produce specific complexes. After we synthesize the complexes, size exclusion chromatography, oxygen binding, thermal denaturation and autoxidation experiments are done to determine the properties of the polymer. In vivo testing is done for polymers that have promising properties.
The second area of interest in the laboratory is targeted photodynamic therapy (PDT). PDT requires light, a photosensitizer and oxygen to produce singlet oxygen that can kill the cell. We are using folate to target specific cancer cell types with PDT agents. We are incorporating hemoglobin into some of the agents to increase the oxygen availability in the target cells. This approach should dramatically decrease side-effects of treatment because it features a double selectivity. Only the tumor cells will take up the PDT agent and the light is only shone on the tumor. The research is interdisciplinary and involves organic synthesis, protein chemistry, cell culture and confocal microscopy.
We are using molecular dynamics simulations to understand the interaction of proteins with ligands. Specifically, we are studying plant and bacterial globins that bind small ligands, like O2, NO and H2S, to determine the pathways for binding and escape from the heme site. We are using three computational techniques (conjugate peak refinement, locally enhanced sampling and implicit ligand sampling) to find these pathways. We study both normal and mutant proteins in collaboration with research groups around the world that do kinetic measurements on these species.
Li, L., Chang, H.-F., Olsen, K. W., Cho, B. P. and Chiarelli, M. P., "Product Ion Studies of Diastereomric Benzo[ghi]fluoranthene-2'-deoxynucleotide Adducts by Electrospray Ionization and Quadrupole Ion Trap Mass Spectrometry," Analyt. Chim. Acta, 557:191-197, 2006.
Tarasov, E., Blaszak, M. M., LaMarre, J. M., and Olsen, K. W., "Synthesis of a Hemoglobin Polymer Containing Antioxidant Enzymes Using Complementary Chemistry of Maleimides and Sulfhydryls," Artif. Cells, Blood Subs. and Biotech., 35:31-43, 2007.
Golden, S. D. and Olsen, K. W., "Use of the Conjugate Peak Refinement Algorithm for Identification of Ligand Binding Pathways in Globins," Methods in Enzymol., 437:417-437, 2008.
Cohen, J., Olsen, K. W., and Schulten, K., "Finding Gas Migration Pathways in Proteins using Implicit Ligand Sampling," Methods in Enzymol., 437:439-457, 2008.
Golden, S. D. and Olsen, K. W., "Identification of Ligand Binding Pathways in Truncated Hemoglobins Using Locally Enhanced Sampling Molecular Dynamics," Methods in Enzymol., 437:459-475, 2008.
Dragan, S.A., Olsen, K. W., Moore, E. G. and Fitch, A., “Spectroelectrochemical study of hemoglobin A, alpha- and beta-fumarate crosslinked hemoglobins; implications to autoxidation reaction,” Bioelctrochem., 73:55-63, 2008.
Estep, T., Bucci, E., Farmer, M., Greenburg, G., Harrington, J., Kim, H. W., Klein, H., Mitchell, P., Nemo, G., Olsen, K., Palmer, A., Valeri, C. R., and Winslow, R., “Basic science focus on blood substitutes: a summary of the NHLBI Division of Blood Diseases and ResourcesWorking Group Workshop,March 1, 2006,” Transfusion, 48:776-782, 2008.
Bobofchak, K. M., Tarasov, E., and Olsen, K. W. “Effect of Cross-linker Length on the Stability of Hemoglobin,” Biochim. Biophys. Acta, 1784:1410-1414, 2008