Regina M. Murphy Smith-Bascom Professor Address/E-mail Program Affiliations Courses Education Fields of Interest Publications Awards & Honors Summary For additional information, see my

Contact Information

3635 Engineering Hall 1415 Engineering Drive Madison, WI 53706

Tel: 608/262-1587 E-mail: regina@engr.wisc.edu

Program Affiliations

• Chemical and Biological Engineering
• Biomedical Engineering

• Biomedical Engineering Center for Translational Research
• Biophysics Program
• Center for Neuroscience

Courses

• CBE 250: Process Synthesis
• CBE 426: Mass Transfer Operations
• CBE 560: Biochemical Engineering
• CBE 561: Biomolecular Engineering Laboratory

Education

• S.B., Ph.D., Massachusetts Institute of Technology

Fields of Interest

• targeted drug design
• physical chemistry of protein-protein interactions

Publications

• "A Strategy for Designing Inhibitors of ß-Amyloid Toxicity," (with J. Ghanta, C.-L. Shen and L.L. Kiesling), Journal of Biological Chemistry, 271 29525-29528 (1996).
• "Static and Dynamic Light Scattering of Biomacromolecules: What Can We Learn?" Current Opinion in Biotechnology, 8 25-30 (1997).
• "Quantitative Analysis of Protein Synthesis Inhibition and Recovery for CRM107 Immunotoxins," (with L.A. Wenning and P. T.Yazdi), Biotechnol. Bioeng., 57 484-496 (1998).
• "Recognition Sequence Design for Peptidyl Modulators of ß-Amyloid Aggregation and Toxicity," (with M.M. Pallitto, J. Ghanta, P. Heinzelman, and L.L. Kiessling), Biochemistry, 38 3570-3578 (1999).
• "Coupled Cellular Trafficking and Diffusional Limitations in Delivery of Immunotoxins to Multicell Tumor Spheroids," (with L.A. Wenning), Biotechnol. Bioeng., 62 562-575 (1999).
• "Probing the Kinetics of Amyloid Self-Association," (with M.M. Pallitto), J. Struct. Biol., 130, 109-122 (2000).
• "Correlation of ß-Amyloid Aggregate Size and Hydrophobicity with Decreased Bilayer Fluidity of Model Membranes," (with J.J. Kremer, M.M. Pallitto, D.J. Sklansky), Biochemistry, 39, 10309-10318 (2000).
• "Structure-Function Relationships for Inhibitors of ß-Amyloid Toxicity Containing the Recognition Sequence KLVFF," (with T.L. Lowe, A. Strzelec and L.L. Kiessling), Biochemistry, 40, 7882-7889 (2001).
• "Profile of Changes in Lipid Bilayer Structure Caused by ß-Amyloid Peptide," (with J.J. Kremer and D.J. Sklansky), Biochemistry, 40, 8563-8571 (2001).
• "Synthesis and Characterization of Membrane-Active GALA-OKT9 Conjugates," (with J. Kuehne), Bioconjugate Chemistry, in press.
• "A Mathematical Model of the Kinetics of ß-Amyloid Fibril Growth from the Denatured State," (with M.M. Pallitto), Biophysical Journal, 81, 1805-1822 (2001).

Selected Awards, Honors and Societies

• NSF Presidential Young Investigator Award (1990)
• Alumni Teaching Quality Award (1992)
• S.C. Johnson Distinguished Fellow Award (1997)
• Jordi Folch-Pi Award, American Society for Neurochemistry (1998)
• Romnes Faculty Fellow (1999)

Summary

Protein-protein and protein-cell interactions regulate physiological systems. My research group is interested in the following: 1) investigating protein-protein and protein-cell interactions using physicochemical and biological experimental techniques, 2) developing quantitative models to describe them, and 3) using this knowledge to develop new, effective therapies.

Protein aggregation plays a key role in the control of many physiological systems. Our current primary interest is in aggregation of a class of proteins known as amyloidogenic proteins. Aggregation of ß-amyloid peptide into fibrils has been implicated in the onset of the neuropathology associated with Alzheimer's disease.

Using a variety of biophysical techniques, we are characterizing the mechanism and kinetics of aggregation of ß-amyloid peptide, and the structure of the fibrillar aggregates. This detailed analysis at the molecular level is critical in order to establish the role of aggregation in the toxic response, and to develop rational strategies for therapeutic intervention. We have begun to address the question as to why aggregated ß-amyloid is neurotoxic. Recently our efforts have focused on the interactions of ß-amyloid with cell membranes. Early data suggest that aggregated but not monomeric ß-amyloid binds to the lipid component of cell membranes. Using sophisticated biophysical tools we are now pursuing a detailed description of how ß-amyloid fibrils associate with the lipid bilayer.

In collaboration with Professor Laura Kiessling in the Department of Chemistry, we are developing strategies for rational design of inhibitors of ß-amyloid toxicity. We have synthesized and tested a series of novel peptide-based compounds, and have shown that these compounds are capable of inhibiting ß-amyloid toxicity in cell culture. We are currently investigating the effect of these inhibitors on ß-amyloid aggregation, and developing second-generation inhibitors.

Targeted drug technology is the other primary focus of my group. We are specifically interested in improving the efficacy of immunotoxins and related molecules for cell-specific killing. In one project, we are studying the kinetic pathways for cellular processing of antibody-toxin conjugates. Experimental results are used to construct a mathematical model of the binding and intracellular processing of these conjugates, and to relate cellular processing to the effectiveness of the immunotoxin. This work has led to the identification of key rate-limiting steps in delivery of immunotoxins to the ribosomes. We are developing strategies for chemical modification of the immunotoxins to reroute them intracellularly, in order to enhance their toxicity. Our approach is to attach peptides to immunotoxins which are designed to specifically interact with intracellular receptors, or to disrupt intracellular membranes.

Copyright 2008 The Board of Regents of the University of Wisconsin System Date last modified: 19-Aug-2011 Content by: regina@engr.wisc.edu Accessibility Web services SEND AN UPDATE REQUEST.