Samuel Kirkwood Professor of Biochemistry

Research Interests   Membrane Binding Proteins; Blood Coagulation; Proteomics

There are two major areas of research in the Nelsestuen lab:  

1. Understand biophysical and physiological roles of protein-membrane binding in blood coagulation and other complex events.   We wish to understand the structural interactions between proteins and the membrane surface and determine how these interactions influence the enzyme activity of various enzyme systems. We use a combination of physical methods such as fluorescence and light scattering plus enzyme kinetics to investigate systems ranging from blood coagulation to enzymes of intact bacteria. Recent studies have produced mutants of vitamin K-dependent blood clotting proteins with enhanced affinity for membranes. These proteins have enhanced function under many circumstances, making them valuable research tools with potential to act as drugs for improved protein therapy in both bleeding and thrombosis disease.
2. As the director of the Center for Mass Spectrometry and Proteomics (MSP, http://cbs.umn.edu/msp/ ), the revolution in mass spectrometry has a major impact on our work as well as that of many investigators at the University. Equipped with the latest instrumentation, we are collaborating with many physician scientists to pursue biomarkers of disease.   Current examples include protein biomarkers of lung transplant rejection, kidney transplant rejection, kidney disease in general, obesity, insulin resistance, inflammation and others.   The objectives are to identify biomarkers that can be used for diagnosis or prognosis and to better understand the mechanisms of that disease.

Nelsestuen, G. L. (June 8, 2004) “Modified Vitamin K-dependent polypeptides” U.S. Patent 6,747,003. (Electronic)

Nelsestuen, G. L., Martinez, M. B., Hertz, M. I., Savik, K, and Wendt, C. H. (2005) “Human Neutrophil alpha-Defensins: A Biomarker of Chronic Lung Allograft Rejection” PROTEOMICS 5, 1705-1713. (Electronic)

Nelsestuen, G. L., Kasthuri, R. S., Zhang, Y., Key, N. S., Jilma, B. (2005) “Plasma protein profiling reveals unique and stable features for each individual” PROTEOMICS 5, 4012-4024. (Electronic)

Matthew D. Stone, Stephen B. Harvey, Michael B. Martinez, Ron Bach and Gary L. Nelsestuen (2005) “Large Enhancement of Functional Activity of Active Site-Inhibited Factor VIIa Due to Protein Dimerization: Insights into Mechanism of Assembly/Disassembly from Tissue Factor” Biochemistry 44, 6321-6340. (Electronic)

Yan Zhang, Matthew Wroblewski, Marshall I. Hertz, Christine H. Wendt, Tereza M. Cervenka and Gary L. Nelsestuen (2005) “Analysis of chronic lung transplant rejection by MALDI-TOF profiles of bronchoalveolar lavage fluid” PROTEOMICS, 6, 1001-1010. (Electronic)

Raj S. Kasthuri, Michael R. Verneris, Hassan N. Ibrahim, Bernd Jilma and Gary L. Nelsestuen (2006) “Studying multiple protein profiles over time to assess biomarker validity.” Expert review of Proteomics, August issue.