Brett Harper is a former Solouki group Postdoctoral Scholar in the Department of Chemistry & Biochemistry at Baylor University. He completed his bachelors at Baylor University in May 2012 with a B.S. in Biology and a minor in Chemistry and his Ph.D. at Baylor University in May 2016 in Biomedical Studies. Brett lived in Fort Worth, Texas, before coming to Baylor University. He joined the team in January 2012 as an undergraduate student and stayed with the group for his graduate and postdoctoral studies.
About Me
“I see the development of sound scientific practices in cutting edge fields (such as mass and ion mobility spectrometry) as essential for the growth and development of communities and economies. Therefore, one of my long term goals is to help train and equip scientists in third world and developing countries, with a specific focus on communities in equatorial Africa, with skills and equipment which are currently lacking or even non-existent. I have seen firsthand the effects of poor healthcare and scientific development. For example, in Uganda I encountered ailments ranging from elephantiasis (from lymphatic filariasis) to untreated goiter and maxillofacial tumors. Most of these disorders could have been easily detected and treated prior to development of any symptoms but were not treated due to lack of technology and healthcare infrastructure. I believe that mass spectrometry and allied techniques are essential tools to diagnose and characterize disease process and treatments in both developing and developed nations. Therefore, the focus of my research is on developing methods to rapidly and accurately characterize the identity, structure, and conformations of biomolecules such as proteins/peptides, DNA, pharmaceuticals and biologics, sugars, and whole cell extracts.
Outside of the lab I enjoy reading, kayaking, hiking, playing disk golf, and during extended breaks (which rarely happens anymore!) traveling.”
Postdoctoral Research
Detection of Conformational Biomarkers in Human Saliva
“The focus of my postdoctoral research was on the detection of conformational biomarkers in human saliva. We utilized ion mobility-mass spectrometry (IM-MS) techniques and in-house developed software (e.g., Anal. Chem. Acta 2016, 941, 49-60) to detect and characterize proteins and other biomolecules which have multiple conformations. The long term goal of this project is to apply this technique to the early detection of various diseases including brain cancers.”
Applications of Chemometric Deconvolution of Ion Mobility Unresolved Isomers
“Our lab has been investigating the utility of chemometric deconvolution of ion mobility (IM) unresolved isomers using post-IM collision-induced dissociation (CID). My recent projects utilizing this technique include monitoring neutral carbonyl losses from various backbone positions of peptide fragment ions [JASMS 2014, 25(10), 1716-1729], improving sequence coverage of unresolved peptide isomers, and extracting conformational information (i.e., collision cross-sections) of unresolved isomer/conformer populations [Anal. Chem. Acta 2016, 939, 64-72]. This technique has potential to be used for monitoring biologics for appropriate folding, assessing disease progression in conformational diseases (e.g., prion type diseases), and improving overall workflow and chemical characterization for analysis of complex mixtures.”
Graduate and Undergraduate Research
Sequence-scrambling of y-Type Peptide Fragment Ions Upon Collision-induced Dissociation
“It has been well established by our lab and others that the amino acid order of b-type peptide fragment ions (Roepstorff’s nomenclature) can rearrange during collision induced-dissociation (CID). Until recently it was believed that sequence-scrambling did not occur during CID of y-type fragment ions. In 2012 we demonstrated, for the first time, that y-type fragment ions can also undergo sequence-scrambling upon CID [JASMS 2012, 24(11), 1755]. While answering reviewer comments I noticed a small peak in the CID mass spectra of a y-type ion from an isotopically labeled peptide which could only correspond to loss of an internal carbonyl group. After further investigation, we found that loss of CO from internal positions is a common occurrence during CID of y-type ions and that many of these fragment ions may wrongly be identified as a-type ions [JASMS 2014, 25(10), 1716-1729]. These studies have implications for peptide/protein sequencing where accurate identification of fragment ions is essential to the quality of protein analysis and identification.”
Gas-phase Rearrangement of DNA Fragment Ions Upon Collision-induced Dissociation
“While much effort has been spent to understand the gas-phase fragmentation behaviors (and misbehaviors in the case of “sequence-scrambling”) of peptide/protein ions, fewer studies have focused on analysis of less common dissociation pathways of oligonucleotide ions. Similar to our investigations of sequence-rearrangements in collision-induced dissociation (CID) of peptide ions, we are also studying nucleotide rearrangements in CID of DNA fragment ions. Our experimental results indicate that atomic rearrangements also occur in CID of DNA ions [JASMS 2015, 26(8), 1404-1413]. ”
Spray Pump Ionization
“In order for mass spectrometry to be readily utilized for field analysis, instrument components must be portable, cheap, easy to use, and consume little-to-no power. Based on results from electrospray ionization (ESI) and sonic-spray ionization (SSI) I decided to develop an easy to use atmospheric pressure ionization technique utilizing a disposable spray pump bottle (similar to methods used in early ion mobility studies prior to the development of ESI). We have tested technique (called spray pump ionization (SPI)) on time-of-flight and Orbitrap systems and generated reproducible signals simply by spraying the sample in front of the atmospheric pressure inlet. While advantageous for portable systems, the technique has lower sensitivity than other ionization techniques. Data presented from this project was awarded the first-place poster prize at the Pan Africa Chemistry Network (PACN) conference in Nairobi, Kenya in November of 2015.
Other Skills Not Listed:
“In addition to tandem mass spectrometry and ion mobility spectrometry, I also have experience with gas-phase and solution-phase hydrogen/deuterium exchange (HDX), high performance liquid chromatography (HPLC), Fourier transform- ion cyclotron resonance mass spectrometry (FT-ICR), high powered lasers, high magnetic fields (9.4 T), human tissue extraction, and instrument design/modification/development. I also have experience mentoring undergraduates in both research and teaching labs.”
Publications
1. Harper, B., Neumann, E. K., Stow, S. M., May, J. C., McLean, J. A., Solouki, T. “Determination of Ion Mobility Collision Cross Sections of Unresolved Isomeric Mixtures Using Tandem Mass Spectrometry and Chemometric Deconvolution.” Analytica Chemica Acta 2016, 939, 64-72.
2. Brantley, M., Pettit, M., Harper, B., Brown, B., Solouki, T., “Automated Peak Width Measurements for Targeted Analysis of Ion Mobility Unresolved Species.” Analytica Chemica Acta 2016, 941, 49-60.
3. Pettit, M., Harper, B.,Brantley, M., Solouki, T., “Collision-energy Resolved Ion Mobility Characterization of Isomeric Mixtures.” Analyst 2015, 140, 6886-6896.
4. Harper, B., Neumann, E. K., Solouki, T. “DNA Oligonucleotide Fragment Ion Rearrangements Upon Collision-induced Dissociation.” Journal of the American Society for Mass Spectrometry2015, 26(8), 1404-1413.
5. Brantley, M., Zekavat, B., Harper, B., Mason, R., Solouki, T. “Automated Deconvolution of Overlapped Ion Mobility Profiles.”Journal of the American Society for Mass Spectrometry2014, 25(10) 1810-9.
6. Harper, B., Miladi, M., Solouki, T. “Loss of Internal Backbone Carbonyls: Additional Evidence for Sequence-scrambling in Collision-induced Dissociation of y-Type Ions.” Journal of the American Society for Mass Spectrometry 2014, 25(10), 1716-1729.
7. Miladi, M., Harper, B., Solouki, T. “Evidence for Sequence Scrambling in Collision-Induced Dissociation of y-Type Fragment Ions.” Journal of the American Society for Mass Spectrometry2013, 24(11), 1755-1766.
Oral Presentations (presenting author underlined)
1. Neumann, E. K.; Harper, B.; Solouki, T. “Phosphopurine Ion Formation Upon Collision Induced Dissociation of DNA Oligonucleotides” 2015 Chemistry and Biochemistry Undergraduate Research Symposium, 2015, Waco, TX. (won first-place for undergraduate research presentation)
2. Brown, B.; Harper, B.; Solouki, T. “Utilizing Ion Mobility Profiles for Rapid identification of Co-eluting Multiple Conformers and Structural Isomers” 2015 Chemistry and Biochemistry Undergraduate Research Symposium, 2015, Waco, TX. (won third-place for undergraduate research presentation)
3. Harper, B.; Neumann, E. K.; Solouki, T. “Improving Sequence Coverage of Ion Mobility Unresolved Peptide Isomers Using Chemometric Data Deconvolution” Pittsburgh Conference, 2015, New Orleans, LA.
4. Harper, B.; Miladi, M.; Zekavat, B.; Solouki, T. “Advanced “X-Omics” Research” Enhancing Research Through Collaboration Retreat, 2013, Waco, TX.
Poster Presentations (presenting author underlined):
1. Harper, B.; Lochridge, J.; Solouki, T. “Spray Pump Ionization: A Simple-to-Use and Low Cost Ionization Technique for Regulatory and Formulation Mass Spectrometry Analysis of Pharmaceuticals.” Pan Africa Chemistry Network (PACN) Congress 2015 – Healthcare: From Discovery to Delivery, 2015, Nairobi, Kenya
2. Harper, B.; Lochridge, J.; Solouki, T. “Saliva Characterization for Non-invasive and Rapid Biomarker Analysis Using Ion Mobility-Mass Spectrometry.” Pan Africa Chemistry Network (PACN) Congress 2015 – Healthcare: From Discovery to Delivery, 2015, Nairobi, Kenya
3. Harper, B.; Brown, B.; Solouki, T. “Rapid Profiling of Cellular Extracts Using Ion Mobility-Mass Spectrometry.” 64th Annual American Society for Mass Spectrometry Conference, 2016, San Antonio, TX. FIRST PLACE PRIZE!
4. Brantley, M.; Pettit, M.; Harper, B.; Brown, B.; Solouki, T. “Peak Width Analysis for Automated Detection of Unresolved Isomers in Ion Mobility.” 64th Annual American Society for Mass Spectrometry Conference, 2016, San Antonio, TX.
5. Harper, B.; Neumann, E. K.; Solouki, T. “Extracting Collision Cross-sections of Ion Mobility Unresolved Isomers using Tandem Mass Spectrometry and Chemometric Deconvolution.” Proceedings of the 63rd ASMS Conference on Mass Spectrometry and Allied Topics, 2015, St. Louis, MO.
6. Pettit, M. E.; Harper, B.; Brantley, M. R.; Solouki, T. “Collision-Energy Resolved Ion Mobility Deconvolution of a Ternary Isomeric Mixture” Pittsburgh Conference, 2015, New Orleans, LA.
7. Harper, B.; Lochridge, J.; Solouki, T. “Spray Pump Ionization Mass Spectrometry of Pharmaceutical, Peptide, and Protein Ions” Pittsburgh Conference, 2015, New Orleans, LA.
8. Harper, B.; Brantley, M.; Pettit, M.; Solouki, T. “Automated Collision Cross Section Calculation for Traveling Wave Ion Mobility Spectrometry Instruments” Proceedings of the 62nd ASMS Conference on Mass Spectrometry and Allied Topics, 2014, Baltimore, MD.
9. Harper, B.; Zekavat, B.; Brantley, M.; Pettit, M.; Solouki, T.“Energy Resolved Ion Mobility Deconvolution of Isobaric Compounds” Proceedings of the 62ndASMS Conference on Mass Spectrometry and Allied Topics, 2014, Baltimore, MD.
10. Harper, B.; Neumann, E. K.; Olaitan, A. D.; Solouki, T. “Sequence-scrambling in Collision-induced Dissociation of Oligonucleotides” Proceedings of the 62ndASMS Conference on Mass Spectrometry and Allied Topics, 2014, Baltimore, MD.
11. Zekavat, B.; Harper, B.; Brantley, M.; Pettit, M. E.; Solouki, T. “Use of Multivariate Curve Resolution and Ion Mobility-Mass Spectrometry for Isomer Differentiation” Proceedings of the 62nd ASMS Conference on Mass Spectrometry and Allied Topics, 2014, Baltimore, MD.
12. Harper, B.; Miladi, M.; Solouki, T. “Evidence for y-type fragment ion rearrangement through loss of internal backbone carbonyl upon collision-induced dissociation”69th Southwest Regional Meeting of the American Chemical Society, 2013, Waco, TX.
13. Harper, B.; Zekavat, B.; Solouki, T. “Human Neutrophil α-Defensins as Potential Stress Biomarkers” Baylor University Scholars Week, Undergraduate Research and Scholarly Achievement, 2013, Waco, TX. (asked to re-present poster from summer 2012)
14. Harper, B.; Zekavat, B.; Solouki, T. “Human Neutrophil α-Defensins as Potential Stress Biomarkers” Baylor University Summer Undergraduate Research and Scholarly Achievement, 2012, Waco, TX.
15. Harper, B.; Miladi, M.; Zekavat, B.; Solouki, T. “Probing the Effect of Primary Structure Variance on the Gas-Phase Conformations of Insulin and Lispro” 61st Annual American Society for Mass Spectrometry Conference,2013, Minneapolis, MN.
16. Miladi, M.; Harper, B.; Solouki, T. “Sequence Scrambling in Collision-Induced Dissociation of y-Type Fragment Ions” 61st Annual American Society for Mass Spectrometry Conference,2013, Minneapolis, MN.
Contact Information
b_harper@alumni.baylor.edu
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