Mass spectrometry (MS)-based proteomics and metabolomics enable broad, in-depth profiling of biomolecules and their abundances, and are critical for understanding cellular structure and function. However, due to sensitivity and throughput limitations, samples comprising a minimum of several thousand cells are generally required for global ‘omics’ measurements, and each analysis can require hours to complete. Recent advances in enabling technologies such as single-cell imaging offer some promise towards biomolecular characterization of tissue microenvironments, but these technologies share a common shortcoming in that only a limited number of molecular species can be analyzed. New technology is crucially needed that combines depth of coverage and ultra-high throughput.
My laboratory will focus on extending in-depth biological MS analyses to single cells and beyond. By dramatically increasing measurement sensitivity and throughput, we will be able to generate biomolecular maps comprising thousands of molecules within biological tissues at single cell resolution. This will provide understand of the influence of tissue organization and microenvironments on the molecular state of cells within those tissues, providing a wealth of information regarding developmental biology, disease development and heterogeneous responses to treatment among different cell types and microenvironments.
Achieving these long-term goals requires advances in sample preparation, separation, ionization and mass analysis. As such, our research efforts will span multiple technologies including robotics and microfluidics for nanoscale sample preparation, improved liquid-phase separations (e.g., liquid chromatography and capillary electrophoresis), increasing the efficiency of nanoelectrospray ionization, and enhancing ion transmission and mass analysis. We will apply these nanoscale omic measurements to a variety of biological systems, working in close collaboration with biologists and clinicians.