Project title: Modeling NETs using adult stem cell-derived organoids

General Description

We aim to elucidate the pathways and mechanisms that lead to NE malignancy and to uncover therapeutic vulnerabilities that may be exploited for treatment. We will, therefore, generate a ‘living biobank’ of intestinal carcinoid and pancreatic neuroendocrine tumor (NET) organoids. In conjunction with our biobank efforts, we aim to model carcinoid and pancreatic NETs through genetic engineering of relevant normal organoids. The organoids will be used for genetic, epigenetic, and drug sensitivity analysis. We will, therefore, induce inactivating mutations in a set of NET-associated genes and characterize the molecular and phenotypic consequences of these mutations or sets of mutations. Each of these aims is expected to elucidate mechanisms of NET formation and progression and reveal therapeutic vulnerabilities.