The transforming growth factor b (TGFb) superfamily includes bone morphogenetic proteins, activins and TGF-b sensu stricto (s.s.). These ligands have been shown to play a key role in numerous biological processes including early embryonic development and immune regulation. They transduce their signal through a hetromeric complex of type I and type II receptors. Such receptors have been identifi...

Abstract IgE mediated mast cell activation is a key feature of allergic disease, although the mechanisms that govern homeostasis are not fully understood. The TGFb signaling pathway has been shown to regulate effector function. Furthermore, variants in associated with diseases; regulation likely involved allergy diathesis. Patients Loeys Dietz Syndrome (LDS), disorder caused by loss function TG...

Radiotherapy (RT) is employed to achieve local cancer control. However, in rare patients, regression of metastases outside of the radiation field has been reported after irradiation of one tumor site, a phenomenon known as abscopal effect. We have previously shown in experimental tumor models that the abscopal effect is mediated by activation of anti-tumor immune responses by radiotherapy, whic...

The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diamete...

Metastatic breast cancer is the second leading cause of cancerrelated deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Because previous ...

Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to leave the primary tumor site, invade surrounding tissue, and establish distant metastases. A hallmark of EMT is the loss of E-cadherin expression, and onemajor signal for the induction of EMT is TGFb, which is dysregulated in up to 40% of hepatocellular carcinoma (HCC). We have constructed an EMT n...

Primary cancer cell dissemination is a key event during the metastatic cascade, but context-specific determinants of this process remain largely undefined. Multiple reports have suggested that the p53 (TP53) family member p63 (TP63) plays an antimetastatic role through its minor epithelial isoform containing the N-terminal transactivation domain (TAp63). However, the role and contribution of th...

The TGFb superfamily regulates a broad range of cellular processes, including proliferation, cell-fate specification, differentiation, and migration. Molecular mechanisms underlying this high degree of pleiotropy and cell-type specificity are not well understood. The TGFb family is composed of two branches: (i) TGFbs, activins, and nodals, which signal through SMAD2/3, and (ii) bone morphogenet...

CD8 T cell anergy is a critical mechanism of peripheral tolerance, poorly investigated in response to immunotherapy. Here, using a pancreatic islet allograft model and CD3 antibody therapy, we showed, by single cell gene profiling, that intragraft CD8 lymphocytes coexpressing granzyme B and perforin were selectively depleted through the Fas/FasL pathway. This step led to long-standing anergy of...