Publications by authors named "D J Kappes"
Article Synopsis
- - Despite advances in breast cancer research, treatment for metastatic disease remains difficult, highlighting the need for better understanding of tumor progression and invasive behavior.
- - Researchers focused on super-enhancers (SEs), which control important cancer-related genes, to identify critical regulators in breast cancer cells, leading to the discovery of ThPOK as a significant master regulator.
- - ThPOK is more prevalent in luminal breast cancer and helps maintain a less invasive epithelial state by inhibiting genes tied to processes like epithelial-mesenchymal transition (EMT), suggesting that targeting ThPOK could be a potential therapeutic approach for limiting metastasis.
In T cells, stromal interaction molecule (STIM) and Orai are dispensable for conventional T cell development, but critical for activation and differentiation. This review focuses on novel STIM-dependent mechanisms for control of Ca signals during T cell activation and its impact on mitochondrial function and transcriptional activation for control of T cell differentiation and function. We highlight areas that require further work including the roles of plasma membrane Ca ATPase (PMCA) and partner of STIM1 (POST) in controlling Orai function.
View Article and Find Full Text PDFThe transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with single-cell RNA-sequencing, progenitor transfer and colony assays, we show that ThPOK controls monocyte-dendritic cell versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered messenger RNA splicing to reprogram intron retention.
View Article and Find Full Text PDFInterferon-gamma (IFNG) has long been regarded as the flag-bearer for the anti-cancer immunosurveillance mechanisms. However, relatively recent studies have suggested a dual role of IFNG, albeit there is no direct experimental evidence for its potential pro-tumor functions. Here we provide in vivo evidence that treatment of mouse melanoma cell lines with Ifng enhances their tumorigenicity and metastasis in lung colonization allograft assays performed in immunocompetent syngeneic host mice, but not in immunocompromised host mice.
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