Education
1994 B.S., Molecular Biology, Union College

1995 B.S., Biochemistry, Union College

1999 Ph.D., Analytical Chemistry, University of Nebraska-Lincoln

Honors & Awards
Sigma Xi Young Investigator Award, New Mexico Chapter, May 2005

Fellow, European Molecular Biology Organization

Research Interests

Research in the laboratory centers on the use of state-of-the-art mass spectrometry (MS) to study the conformations and movements of proteins and protein machines.  Mass spectrometry can be used to study protein conformation if the proteins in question are labeled with a structure-dependent labeling method such as amide hydrogen exchange (HX).

Proteins contain a number of hydrogens that can exchange with hydrogen in the surrounding solvent.  The most useful hydrogen to follow is the backbone amide hydrogen.  If the normal H2O solvent is changed to D2O, the protein gradually becomes deuterated.  Because deuterium and hydrogen differ in mass by 1 dalton, the incorporation of deuterium (aka, hydrogen exchange) into a protein can be monitored with high resolution mass spectrometry.

The rate of HX depends on hydrogen bonding and solvent accessibility.  Folded proteins can have amino acids with HX rates as much as 1 billion times slower than the same amino acid that is not in a folded protein.  Protein folding and unfolding, whether in cells or in the test tube, represent large changes in protein structure, hydrogen bonding and solvent accessibility that can be investigated with HX MS.  Smaller structural changes critical for protein function can also be probed with HX MS. 

Recent projects have included analysis of conformation and dynamics in
the Src-family of tyrosine kinases, investigations of therapeutic drug binding to the Abl tyrosine kinase, probing partially unstructured viral accessory proteins from HIV and Herpes, and characterization of
recombinant therapeutic proteins that are of interest to the biopharmaceutical industry." 

Selected Publications

Wales, T. E., Fadgen, K. E., Gerhardt, G. C. & Engen, J. R. (2008). High-speed and high-resolution UPLC separation at zero degrees Celsius. Anal. Chem. 80(17), 6815-6820. Pubmed: 18672890.

Chen, S., O’Reilly, L. P., Smithgall, T. E. & Engen, J. R. (2008). Tyrosine Phosphorylation in the SH3 Domain Disrupts Negative Regulatory Interactions within the c-Abl Kinase Core. J. Mol. Biol. 383(2),
414-423. Pubmed: 18775435.

Wales, T. E & Engen, J. R. (2006). Hydrogen exchange mass spectrometry for the analysis of protein dynamics. Mass Spectrom. Rev. 25(1), 158-170. Pubmed: 16208684.