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.