Speaker: Lance A. Liotta, George Mason University
Topic: Mapping tumor tissue communication networks for designer therapies
Date: Monday, February 9, 2026
Time: 6:15 pm Dinner, 7:15 pm Presentation
Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)
Dinner: Please RSVP to Sheng Feng (SFeng@som.umaryland.edu) by Friday, February 6 if you will be attending the dinner.
Abstract: We envision a future in which spatial molecular portraits of the tumor tissue microenvironment can transcend static lists of analytes to become integrated maps of active cellular signaling networks. Spatial proteomic profiling of the cancer tissue microenvironment can be conducted on bothd the cellular and interstitial compartments as a means of eavesdropping on the ongoing tumor-host communications. Active in-use kinase pathways can be reconstructed by evaluating linked intracellular phosphorylated kinase substrates. Communication between the tissue tumor cells and the downstream sentinel lymph node can be studied by molecular analysis of extracellular vesicles shed into the interstitial space between cells. This combined analytical approach has succeeded in generating predictors of complete pathologic response for personalized therapy. Moreover, understanding the network spatial topology can pinpoint therapeutic targets that may be oncogenic drivers. A second revolution currently underway is the development of synthetic molecular therapies. Based on recent advances in AI, and DNA/protein folding coding, it is now possible to rapidly synthesize a therapeutic molecule that matches the 3-D face of the therapeutic target. A successful version of this approach uses DNA origami as a backbone to present protein ligands matching the hot-spots of the therapeutic target. The artificial molecule can achieve high sensitivity and specificity because its specific 3-D shape is sculptured in silico and then mass produced. Thus, we can image a future in which tissue spatial analytics reveals candidate individual molecular targets specific to a tumor biospecimen. If no drug exists for the target, we can design a matching antagonist or agonist molecule tailored to that tumor’s functional driver.
Lightning Talk
Characterizing the Effects of Protein Glycosylation Perturbation on Phosphorylation Signaling
Effram Wei
Johns Hopkins University
Protein glycosylation and phosphorylation constitute two pervasive regulatory layers in mammalian cells, yet the effects that protein glycosylation play in phosphorylation signaling remain poorly understood. Here we show that controlled perturbation of N-linked glycan biosynthesis through glycoengineering fundamentally rewires phosphorylation signaling networks in human cells. Using comprehensive proteomics approaches, we simultaneously profiled the global proteome, glycoproteome, and phosphoproteome in engineered HEK293 cells designed to eliminate core fucosylation while enhancing sialylation and reducing GlcNAc branching complexity. Glycoengineering emerged as the dominant source of molecular variation across all datasets, with over 9,800 intact glycopeptides identified of which 3,400 are significantly altered, establishing a remodeled baseline cellular state. Upon serum stimulation, engineered cells not only exhibited markedly decreased phosphorylation responses compared to wild-type cells, but comprehensively re-wired to prefer signaling away from canonical EGFR/mTOR growth pathways. These findings establish a systematic framework for targeting glycosylation-phosphorylation regulation and nominate glycan-dependent signaling nodes as potential therapeutic vulnerabilities in glycosylation-remodeled disease states.
