Rosalie C. Sears

MYC targeted de novo binders impair tumor growth

MYC is one of the most frequently dysregulated oncogenic drivers across many cancers, yet direct therapeutic targeting has remained difficult because its function is mediated by disordered regions and transient protein-protein interactions. Here we design proteins that bind epitopes within regions of MYC whose sequence...

Clonal heterogeneity in human pancreatic ductal adenocarcinoma and its impact on tumor progression.

Abstract A120: Tumor-intrinsic MYC promotes a skeletal muscle-involving wasting phenotype in pancreatic ductal adenocarcinoma

Cancer cachexia is defined by an ongoing loss of skeletal muscle mass, with or without loss of adipose tissue, and is particularly prevalent and severe in pancreatic ductal adenocarcinoma (PDAC). However, whether muscle and adipose wasting represent separable components of cachexia and are differentially shaped by tu...

Epigenetic progression of pancreatic cancer to aggressive subtypes involves alternate routes of lineage reprogramming in subtype-intermediate progenitor cells

IFNγ-dependent tumor-cell MHC-II is restrained by MAPK signaling and associated with immunotherapy responsiveness in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME) and poor prognosis. Although major histocompatibility complex class II (MHC-II) is typically expressed by professional antigen-presenting cells, its regulation and significance in malignant PDAC cells remain un...

Abstract A029: Chromatin accessibility profiling of human pancreatic tumors reveals epigenetic features of malignant and stromal cell subtypes

Pancreatic ductal adenocarcinoma (PDAC) disease progression involves complex cell state transitions in both malignant and non-malignant populations within the tumor microenvironment. To uncover PDAC cell states and epigenetic features associated with clinical outcome, we profiled 40 tumor samples (33 primary tumors a...

The post-transcriptional regulator HuR promotes immune evasion in pancreatic ductal adenocarcinoma.

Overall, it is found that the post-transcriptional regulator HuR facilitates immune evasion in PDAC by constraining T-cell function, identifying HuR blockade as a promising therapeutic strategy in combination with immunotherapies.