Mitochondrial DNA (mtDNA) mutations cause inherited disease, accumulate with age, and recur in tumors, yet their effects remain unresolved because existing models interrogate one engineered allele at a time. We developed mtDIVE, a random C→T mutagenesis platform for pooled mitochondrial forward genetics in human epithe...
Amir Giladi, Ron Baik, Chih-Yao Chung et al.· bioRxiv· 0 citations
Intratumoral heterogeneity is a defining feature of pancreatic ductal adenocarcinoma (PDAC), yet how distinct malignant cell states contribute to tumor behavior and stromal diversity in situ remains poorly understood. PDAC contains recurrent classical and basal states, with basal-dominant tumors associated with aggre...
Kate Ryan, A. Singhal, Samuel A. Rose et al.· Cancer Research· 0 citations
Pancreatic cancer (PC) is largely refractory to immune checkpoint blockade (ICB), although homologous recombination-deficient (HRD) tumors may derive benefit. In the POLAR trial of maintenance pembrolizumab plus olaparib after platinum-based chemotherapy for metastatic PC, responses remained heterogeneous. To define de...
M. Hilmi, J. Schoenfeld, Wilson H. McKerrow et al.· bioRxiv· 0 citations
A pro-tumorigenic IL-1β/IL-6 signaling circuit mediated through local macrophages and fibroblasts is identified that unleashes the full oncogenic potential of a cancer driver activated at the PIN stage, with implications for TME-specific targeted therapeutics in early-stage disease.
Young-Sun Lee, Jimmy L. Zhao, Agnieszka Chryplewicz et al.· bioRxiv· 0 citations
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