Research Overview
Nathan is an experimental analytical chemist who has pioneered advances in ion trap mass spectrometry, proteomics, and cloud computing. Early in his career, Nathan was focused on advancing a new type of mass spectrometer, the quadrupole ion trap, as an ultra-sensitive instrument capable of fully-automated on-line tandem mass spectrometry. He was a principal architect and implementer of the “Ion Catcher Mass Spectrometry” software suite that introduced the use of computer generated scan functions and real-time data acquisition methods to enable tandem mass spectrometry on the chromatographic time scale. These on-line data dependent acquisition methods were later commercialized by Finnigan Corp., are in widespread use today, have heavily influenced the evolution of LC-MS/MS instrumentation, and are fundamental to rapid growth of proteomics research.
After completing his graduate and postdoctoral studies, Nathan joined Merck and Co. Inc. to develop new methods to identify novel drug leads present in complex combinatorial libraries ([11467539],[11607705]). He developed and distributed LibView, a software tool that compared ultra-complex spectra containing hundreds of thousands of drug like molecules to predictive models, enabling subtle changes in structure and abundance could be pin-pointed and identified.
Building on the LibView work, Nathan became fascinated with the unbiased analysis of ultra-complex mixtures and invented experimental and computation approach for comparing biological samples without the use of chemical labels or internal standards. He invented “Differential Mass Spectrometry (dMS)” a label free approach for quantifying and identifying biologically relevant proteins in complex multi-factorial experiments([15481957]). The dMS approach became the foundation for Merck’s proteomic biomarker discovery platform and was applied to large scale biomarker discovery efforts in in neuroscience, metabolic disorders, cardiovascular disease, and other key therapeutic areas([21475673],[20517885],[20028270],[20388904],[18785765],[19367703],[17070068]). Nathan and colleagues industrialized the dMS approach which was later adopted by most major pharma companies as the Elucidator Proteomics Suite sold by Rosetta Biosoftware ([20095649]).
In 2011, Nathan joined the University of Pittsburgh with the goal of enabling large scale proteomics studies in an academic setting. Because dMS requires highly specialized software and significant computational resources, Nathan partnered with Andrey Bondarenko (Infoclinika) to create a cloud-based dMS analysis platform that enables anyone with an internet connection to carry out large scale quantitative proteomics studies. One major focus of Nathan’s laboratory is to develop personalized proteomics technologies that allow individuals to create and monitor their own health by tracking proteomic and metabolic profiles in urine and other clinically accessible bio-fluids.
As the Scientific Director of the Biomedical Mass Spectrometry Center, Nathan seeks out academic collaborations in basic, translational, and clinical research that drive the development of new technologies and innovation, while advancing the use of mass spectrometry at the University of Pittsburgh. Working with investigators from the departments of Cell Biology, Psychiatry, Pathology, Drug Discovery, and the Cancer Institute, our lab is involved in the elucidation of key players in biological pathways, the discovery of molecular targets for novel therapeutics, and identification and translation of candidate biomarkers ([25191796],[24798811],[25433904],[25423885],[24297176],[24019463]).
Mass spectrometry is highly collaborative and multi-disciplined field of study that brings together talented professionals with diverse backgrounds and expertise. If you are passionate about science and enjoy working with others, mass spectrometry can be a great place. Nathan’s lab works closely with companies in the technology and pharmaceutical sectors. Current academic-industrial partnerships include collaborations with New Objective, Infoclinika, University of Washington, Scripps Florida, Bristol Myers Squibb, Novartis, and Merck. Together, Nathan and colleagues are focused on advancing mass spectrometry based technologies and using them to solve important real world applications.