Yuanyuan Zhu, MS (Advisor: Raghu Kalluri, MD, PhD)

Single Cell and Spatial Analysis Characterize Metabolic DPEP1⁺ Fibroblasts in PDAC

     Understanding cancer-associated fibroblasts (CAF) metabolism reprogramming in pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) may uncover novel therapeutic targets. Here, we used single cell and spatial transcriptomics to comprehensively characterize the neoplastic and TME content of human PDAC. CAFs metabotypes and a novel CAF population expressing DPEP1, COMP, CST1, and involved in glutathione metabolism, termed 'gluCAFs', which is associated with poor clinical outcomes and advanced PDAC stages, were characterized. The inhibition of KRAS^G12D and a combination therapy involving a Hedgehog inhibitor, Gemcitabine/Abraxane, and anti-CTLA4 can reprogram DPEP1⁺CAFs in the PDAC TME. Our study presents a high-resolution atlas of PDAC TME and highlights DPEP1⁺CAFs as a novel CAF subtype critical for PDAC progression and susceptibility to KRAS inhibitors and immunotherapy.  

Advisory Committee:

• Raghu Kalluri, MD, PhD, Chair     
• Ken Chen, PhD
• Nicolas Navin, PhD
• Linghua Wang, MD, PhD
• Natividad Roberto Fuentes, Jr. PhD

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Meeting ID: 879 4962 6369

Password: 424480