Advancing cross-linking mass spectrometry to elucidate cellular networks

Speaker

Lan Huang
Professor of physiology and biophysics, University of California, Irvine

Lan Huang is a professor of physiology and biophysics at the University of California, Irvine. Her research centers on developing novel mass spectrometry-based proteomic strategies to study macromolecular protein complexes, especially within the ubiquitin-proteasome system. She pioneered sulfoxide-containing MS-cleavable cross-linkers, establishing a robust cross-linking mass spectrometry, or XL-MS, platform for elucidating protein interaction networks and structural topologies. Her lab’s methodologies have advanced the study of protein–protein interactions in living cells and led to patented, commercially available reagents. Recently, her laboratory has applied XL-MS technologies to clinical samples to uncover disease-relevant protein networks.

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The ASBMB Breakthroughs webinar series offers a window into the cutting-edge biochemistry and molecular biology research driving discovery.

Protein–protein interactions (PPIs) form highly intricate and dynamic networks that underlie virtually all cellular processes. Disruption of these networks can perturb cellular homeostasis and drive disease progression. Systems-level analysis of PPIs is critical for uncovering the molecular mechanisms underlying pathogenesis and identifying interaction-based therapeutic targets. Cross-linking mass spectrometry (XL-MS) uniquely captures native PPIs and simultaneously reveals their identities and physical contacts, without the need for genetic manipulation. Here, we present advancements in MS-cleavable XL-MS technologies and their applications for mapping cellular networks with structural features, offering new insights into the organization of protein complexes in cells.