The Yu Lab

Innovating proteomics

Current Projects

The overarching goal of the lab is to innovate proteomics technologies in order to mechanistically and systematically delineate the intricate proteotype underlying physiological and pathological processes. We are particularly interested in understanding how kinase signaling network mediates the interplay between cancer and aging.

Creating Intelligent Quantitative Proteomics Platforms

Mass spectrometry (MS)-based proteomics has become an essential tool for both qualitative and quantitative analysis. Yet, despite decades of advancements, most proteomics experiments still rely on static, rigid methods that fail to adapt to the unique demands of diverse biological systems, leading to suboptimal sensitivity, accuracy, and throughput. At the Yu Lab at UMass Chan, we are pioneering high-performance, intelligent proteomics technologies by integrating machine learning, enabling research that would otherwise be challenging or impossible. Our current focus is on innovating platforms for large-scale quantitative analysis of precious clinical and animal samples, as well as high-throughput drug discovery.

Unraveling the PTM Landscape in Human Proteome

The human proteome is incredibly complex and dynamic, with an estimated tens of thousands of proteins and an even larger number of proteoforms resulting from post-translational modification (PTM). This complexity and the distinct physiochemical properties of different PTMs makes it challenging to isolate and characterize all the different proteoforms accurately. We strive to create novel mass spectrometry-based platforms to enable fine characterization of PTMs, notably phosphorylation, in different biological and pathological contexts.

Determining Enzyme-Substrate Relationship

The functional redundancy in the human proteome protects against potential disruptions or failures in specific proteins or pathways. Meanwhile, it contributes to the intricacy, leading to complex and unresolved enzyme-substrate relationships and hindering the comprehensive mapping of the cellular signaling network. We leverage proteomics to establish kinase- and ubiquitin ligase-substrate relationships to facilitate better understanding of cell signaling and protein homeostasis.

Unveiling Proteomic Alterations in Health and Disease

Age is a major risk factor for many aging-associated diseases (AADs), including cancer and neurodegeneration. Our mechanistic understanding of the intricate relationship between aging and AADs remains limited. We leverage quantitative proteomics for comprehensive multi-dimensional characterization to dissect the intricate interplay, exploring alterations in protein expression, post-translational modifications (PTMs), protein-protein interactions (PPI), and protein degradation.

Identifying Protein-Ligand Interaction for Drug Discovery

Approximately 80% of the human proteome remains undruggable due to a lack of well-defined binding pockets and ineffectiveness in identifying tractable small-molecule ligands. To address this limitation, we are pioneering novel chemoproteomics strategies aimed at revealing elusive protein-ligand interactions. These interactions can serve as valuable tools to modulate protein functions and, ultimately, pave the way for the development of innovative therapeutics.

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