Background:

• Postdoctoral Fellow, Japan Society for the Promotion of Science, Himeji Institute of Technology, 1992-93
• Postdoctoral Research Associate, Northwestern University, 1993-95.
• Named on Popular Science's 10 Most Brilliant List, 10/2002
• Pittcon Achievement Award, 2002
• Eli Lilly Analytical Chemistry Award (ACS Analytic Chemistry Division), 2000 - 2002
• U.S. Defense Science Study Group (DSSG), 2000 - 2002
• Phi Lamba Upsilon Fresenius Award, 2000
• Arthur F. Findeis Award (ACS, Division of Analytical Chemistry), 1999 - 2000
• Camille Dreyfus Teacher-Scholar Award, 1999
• TR- 100 Research Innovation Award (Technology Review Magazine, MIT), 1999
• Teaching Excellence Recognition Award (IU), 1999
• Frontiers of Science Symposium participant (invited by U.S. National Academy of Science/German von Humboldt Foundation), 1999
• Alfred P. Sloan Research Fellowship, 1998 - 2000
• Indiana University Outstanding Junior Faculty Award, 1997 - 1998
• Finnegan Award (American Society for Mass Spectrometry), 1997
• Porter Science Building Dedication at Adams State College, 1997
• NSF Early Career Award, 1996 - 2000
• Summer Faculty Research Fellowship (IU) 1995

We are interested in the structures of large low-symmetry molecules in the gas phase and the step-by-step motions explaining the connectivity of the various isomers. We are using and developing a variety of techniques—including ion mobility spectrometry, mass spectrometry, lasers, and computer modeling—to separate gas-phase isomers, discern structural information, and follow isomerization processes.

A major area of interest to our group is protein structure. Although the "native" solution structures of many proteins are known, little is known about how denatured forms fold into the native state. This is because isolating and determining structures for a large number of solutions-phase intermediates is difficult. We are approaching this problem quite differently by studying the structures of naked proteins in the gas phase. Although it seems unlikely that proteins in the gas phase will have structures that are identical to those found in solution, it is straightforward to separate gas-phase intermediates and follow the dynamics associated with folding.

It is worth explaining briefly how shape information about biological systems in the gas phase is obtained. The mobility of a charge protein through a high-pressure buffer gas depends on the protein's average collision cross-section, a property defined by its confirmation. By comparing measured mobilities to those calculated for trail conformations, structural information about the gas-phase species can be extracted.

Another area of interest is the rapid and sensitive analysis of mixtures such as those that arise in the field of proteomics. Electrospray ionization provides an efficient means of ionizing many different types of samples. By combining ion mobility methods with mass spectrometry and other separation techniques, we can examine isomers or variations in conformations that are inaccessible by conventional mass spectrometry methods. Current projects include fundamental studies of the fly and human urinary proteomes and analyses of combinational libraries.

	Two-dimensional drift(flight) dataset of the digest mixture from m/z ranges of 510 to 610. The white circles indicate the location of fragment peaks that were observed in the tryptic digestion of horse albumin. Peaks labeled with sequence assignments correspond to tryptic fragments expected from digestion of horse albumin. All peaks that were identified in the individual protein were identified in the mixture except for the peak at m/z=543.8 corresponding to [KQSALAWLVK 2H]2 . This peak cannot be unambiguously identified because of spectral congestion in this region.

Selected Publications:

"Coupling ion mobility separations, collisional activation techniques, and multiple stages of MS for analysis of complex peptide mixtures," with C. S. Hoaglund-Hyzer, Y. J. Lee, and A. E. Counterman. Anal. Chem., 74, 992 (2002).

"Resolving isomeric peptide mixtures: a combined HPLC-ion mobility-TOFMS analysis of a 4000 component combinatorial library," with C. A. Srebalus Barnes, A. E. Hilderbrand, and S. J. Valentine. Anal. Chem., 74, 26 (2002).

"Monitoring structural changes of proteins in an ion trap over ~10-200 ms: unfolding transitions in cytochrome c ions," with E. R. Badman and C. S. Hoaglund-Hyzer. Anal. Chem., 73, 6000 (2001).

"Magic number clusters of serine in the gas phase," with A. E. Counterman. J. Phys. Chem. B, 105, 8092 (2001).

"Large anhydrous polyalanine ions: evidence for extended helices and onset of a more compact state," with A. E. Counterman. J. Am. Chem. Soc., 123, 1490 (2001).

"H/D exchange levels of shape-resolved cytochrome c conformers in the gas phase," with S. J. Valentine. J. Am. Chem. Soc., 119, 3558 (1997).

"Disulfide-intact and -reduced lysozyme in the gas phase: conformations and pathways of folding and unfolding," with S. J. Valentine, J. G. Anderson, and A. D. Ellington. J. Phys. Chem. B, 101, 3891 (1997).

"Characterizing oligosaccharides using injected-ion mobility/mass spectrometry," with Y. Liu. Anal. Chem., 69, 2504 (1997).

"Gas-phase DNA: oligothymidine ion conformers," with C. S. Hoaglund, Y. Liu, A. D. Ellington, and M. Pagel. J. Am. Chem. Soc., 119, 9051 (1997).

"An ion trap interface for ESI-ion mobility experiments," with C. S. Hoaglund and S. J. Valentine. Anal. Chem., 69, 4156 (1997).

"Three-dimensional ion mobility/TOFMS analysis of electrosprayed biomolecules," with C. S. Hoaglund, S. J. Valentine, C. R. Sporleder, and J. P. Reilly. Anal. Chem., 70, 2236 (1998).