BBE Informal Seminar - Dr. Pei Su

"From Tissues to Single Cells: Direct Proteoform Profiling Using Orbitrap-Based Single Molecule Mass Spectrometry"

Direct proteoform measurement in biological samples provides a path to proteomics in spatial tissue compartments and single cells at unprecedented sensitivity and throughput. We employ individual ion mass spectrometry (I2MS), an Orbitrap-based charge detection MS technique in conjunction with direct sampling MS approaches for proteoform profiling in spatial tissue compartments and endogenous single cells directly obtained from tissues. We demonstrate how the collection of single proteoform molecules or their gas-phase fragments over distinct spatial tissue compartments contribute to our understanding of proteoform identification, quantitation, spatial localization, and posttranslational modifications. In particular, proteoform imaging mass spectrometry (PiMS) using nanospray desorption electrospray ionization (nano-DESI) has enabled highly-multiplexed imaging and identification of kidney and ovarian cancer tissue proteoforms up to 70 kDa at ~20 µm spatial resolution. Such approach has been extended to high-throughput single cell profiling at a speed of >1000 cells per day, enabling proteoform-based cell typing in complex cell mixture from rat brain hippocampus. Moreover, we have extended such platform to mid-infrared laser ablation for proteoform and native protein analysis in complex biochemical environments.

Biography: Dr. Pei Su is an assistant professor in the Department of Biochemistry at University of California, Riverside (Department of Bioengineering by courtesy). He earned a Bachelor of Science in Chemistry from Fudan University, Shanghai, China, in 2015. He received his Ph.D. in Analytical Chemistry in December 2020 from Purdue University, West Lafayette, USA, under the

supervision of Prof. Julia Laskin. Prior to his independent career at UC Riverside, he performed postdoctoral training with Prof. Neil Kelleher at Northwestern University as a NIH/NIAID K99/R00 postdoctoral fellow. His research program is inspired by understanding how cellular metabolism shapes the immune system by taking a multimodal single molecule approach combining concepts in analytical chemistry, instrumentation, engineering, bioinformatics and protein biochemistry, with a central emphasis in mass spectrometry-based technologies for proteoform discovery in complex biochemical environments such as tissues, single cells, and subcellular compartments.