Publications by authors named "J D Licht"
The C-terminal PHDVC5HCH tandem domain of NSD2 is a combinatorial reader of unmodified H3K4 and tri-methylated H3K27 that regulates transcription of cell adhesion genes in multiple myeloma.
Nucleic Acids Res
December 2024
Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding.
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- Chromatin structure is crucial for DNA accessibility and gene expression; disrupting it can lead to diseases and cancer.
- H2B variants, which are slightly different from standard H2B histones, have been found to be dysregulated during processes like epithelial to mesenchymal transition and could function as "oncohistones," similar to other histone mutations linked to cancer.
- Research indicates that these H2B variants modify chromatin dynamics and can affect oncogenic gene expression, suggesting they could serve as early cancer biomarkers and potential therapeutic targets.
Article Synopsis
- Oncogenic KRAS signaling is vital in pancreatic ductal adenocarcinoma (PDAC), and previous treatments targeting MEK and BCL-xL were ineffective due to amplified EGFR signaling in patients.
- A new strategy using a triplet therapy involving trametinib (MEK inhibitor), DT2216 (BCL-xL degrader), and afatinib (EGFR inhibitor) showed improved results in killing PDAC cells both in lab tests and in mouse models.
- The combination produced significantly better tumor growth reduction compared to double treatments and highlighted EGFR's role, suggesting this triplet approach warrants clinical testing for PDAC patients.
Genetic variation drives cancer cell adaptation to ECM stiffness.
Proc Natl Acad Sci U S A
September 2024
The progression of many solid tumors is accompanied by temporal and spatial changes in the stiffness of the extracellular matrix (ECM). Cancer cells adapt to soft and stiff ECM through mechanisms that are not fully understood. It is well known that there is significant genetic heterogeneity from cell to cell in tumors, but how ECM stiffness as a parameter might interact with that genetic variation is not known.
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