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Shuangyi Cai
BME PhD Proposal Presentation
Date:2022-06-09
Time: 12:30 pm - 2:30 pm
Location / Meeting Link: Location: EBB 3029 conference room/Bluejeans: https://bluejeans.com/595881301/8115
Committee Members:
Coskun, Ahmet, PhD (Advisor) Kemp, Melissa, PhD Arvanitis, Costas, PhD Sun, Shi-Yong, PhD Wood, Levi B, PhD
Title: Deciphering subcellular signaling networks using image-based protein multiplexing
Abstract:
Non-small cell lung cancer (NSCLC) comprises 80% to 85% of lung cancer, and due to the intrinsic resistance to chemotherapy, the survival rates of NSCLC patients remain unimproved. Both WNT/β-catenin and AKT/mTOR pathways are commonly activated in NSCLC. The EGFR-mutated cells have shown resistance to chemotherapeutic agents. Osimertinib, as the third generation of irreversible TKIs, has shown more efficacy in treating EGFR mutant NSCLC; however, a subset of patients receiving osimertinib has developed relapse and drug resistance due to the activation of MEK/ERK and YAP/TEAD pathways. Therefore, dissecting the signaling pathway crosstalk under drug treatment could reveal the spatial dynamics among WNT/β-catenin, AKT/mTOR, ERK/MEK, and YAP/TEAD pathways. Although current bulk assays could reveal the mechanisms of resistance and protein interactions on a large scale, they fail to show the spatial features in subcellular regions and the spatial correlations between the kinases and their direct substrates. Also, the conventional immunofluorescence is typically limited to 4-6 channels. The overall objective of this research is to screen a large number of signaling proteins and their spatial profiles under different combinations of drug treatments using a rapid multiplexed immunofluorescence (RapMIF) and protein interaction (RapMPI) techniques. We will achieve the objectives with the following specific aims: 1) Optimize the RapMIF approach to quantify the expression and spatial distribution of signaling markers involved in WNT/β-catenin, AKT/mTOR, ERK/MEK, and YAP/TEAD pathways in EGFRm NSCLC cells. 2) Optimize the RapMPI approach to quantify the expression and spatial distribution of PPIs involved in WNT/β-catenin, AKT/mTOR, ERK/MEK, and YAP/TEAD pathways in EGFRm cells. 3) Validate the spatial signaling networks and protein-protein interactions in EGFRm patient and mouse tissues using RapMPI.These multiplexed protein maps could help identify the distinct cell states, cell-to-cell heterogeneity, and complexity in signaling dynamics.
