Gary L.


Emeritus Faculty
Biochemistry Molecular Biology and Biophysics

Research interests
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, 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.
Selected publications

Yan Zhang, Alan R. Sinaiko, Gary L. Nelsestuen (2011). Glycoproteins and Glycosylation: Apolipoprotein C3 Glycoforms by top-down MALDI-TOF Mass Spectrometry" methods in Molecular Biology, in press.

D. W. Mahoney, T. M. Therneau, C. J. Heppelmann, L. Higgins, L. M. Benson, R. M. Zenka, P. Jagtap, G. L. Nelsestuen, H. R. Bergen, A. L. Oberg (2011). Relative Quantification: Characterization of bias, variability and fold changes in mass spectrometry data from iTRAQ labeled peptides. J Proteome Res. PMID: 21755926

S. K. Akkina, Y. Zhang, G. L. Nelsestuen, W. S. Oetting and H. N. Ibrahim (2009). Temporal stability of the urinary proteome after kidney transplant: more sensitive than protein composition? Journal of Proteome Research (special issue on temporal and spatial proteomics) 8, 94-103. PMID: 19012427

S. B. Harvey, Y. Zhang, J. Wilson-Grady, T. Monkkonen, G. L. Nelsestuen, R. S. Kasthuri, M. R. Verneris, T. C. Lund, E. Wesley Ely, G. R. Bernard, H. Zeisler, M. Homoncik, B. Jilma, T. Swan, and T. A. Kellogg (2009). The O-glycoside biomaker of Apolipoprotein C3: responsiveness to obesity, bariatric surgery and therapy with metformin, to chronic or severe liver disease and to mortality in severe sepsis and graft vs. host disease. Journal of Proteome Research (Special issue on Glycoproteomics) 8, 603-612. PMID: 19055479

R. S. Kasthuri, K. R. McMillan, C. Flood-Urdangarin, S. B. Harvey, J. T. Wilson-Grady, and G. L. Nelsestuen (2007). Correlation of a T45S variant of apolipoprotein C1 with elevated BMI in persons of American Indian and Mexican ancestries International Journal of Obesity, 31(8):1334-6. PMID: 17310220

M.S. Wroblewski, J, T. Wilson-Grady, M.B. Martinez, R. S. Kasthuri, K. R. McMillan, C. Flood-Urdangarin, and G. L. Nelsestuen (2006). A functional polymorphism of apolipoprotein C1 detected by mass spectrometry FEBS Journal 273, 4107-4115. PMID: 16981907

Issued patents: G. L. Nelsestuen, US Patents 7,812,132; 7,750,120; 7,662,923; 7,612,188; 7,553,935; 7,553,934; 7,479,551; 7,294,699; 7,314,917; 7,247,708; 7,160,540; 7,220,837; 6,762,286; 6,747,003; 6,693,075; 6,423,826; 6,017,882; patents pending. Three phase 1 clinical trails have neen successfully completed on various technologies.

S. B. Harvey, M. D. Stone, M.B. Martinez, and G. L. Nelsestuen (2003). Mutagenesis of the gamma-Carboxyglutamic Acid Domain of Human Factor VII to Generate Maximum Enhancement of the Membrane Contact Site. J. Biol. Chem. 278, 8363-8369. PMID: 12506121