Gerry Blobe’s research in the TGF-β superfamily signaling field has focused on two long-term research objectives: (1) to define mechanisms for the dichotomous tumor suppressor/tumor promoter role of these pathways in human cancers and (2) to establish novel paradigms for signaling co-receptor function in physiology and human disease. As a model system, his laboratory investigates two related TGF-β superfamily co-receptors, the type III TGF-β receptor, TβRIII, and endoglin. His laboratory has defined TβRIII and endoglin as critical mediators/regulators of TGF-β signaling, including defining novel roles for their conserved cytoplasmic domains in interacting with scaffolding proteins to regulate their expression, internalization and signaling. His lab has also defined a novel role for TβRIII as a suppressor of cancer progression in a broad spectrum of human cancers. These studies have broad impact, improving our ability to target co-receptors and their signaling pathways as diagnostic markers and therapeutic targets.