Publications by authors named "Rucha Modak"
Article Synopsis
- Emerging research highlights how factors in the leukemia microenvironment protect cancer cells from treatments and contribute to drug resistance, signaling the need for targeted therapies in acute myeloid leukemia (AML).
- A study involving around 300 AML patient samples found that higher levels of the cytokine CCL2 correlate with reduced effectiveness of MEK inhibitors, leading to further investigations into the mechanisms behind this resistance.
- The findings suggest that targeting both CCL2 and the MEK pathway can improve treatment responses in AML, proposing a combination therapy as a promising strategy to overcome drug resistance and enhance patient outcomes.
Article Synopsis
- Cell surface proteins are crucial for therapy and cell analysis, but detecting them using mass spectrometry is difficult due to factors like low levels and complex modifications.
- The research team developed a more effective Cell-Surface Capture (CSC) workflow that uses magnetic beads to improve protein identification, testing various labeling conditions and data collection methods.
- This optimized process enabled the identification of approximately 600-900 cell surface proteins from minimal HeLa cell samples and highlighted significant differences in protein profiles between standard cell cultures and tumor models, potentially aiding drug target discovery.
B3GNT2 is responsible for elongation of cell surface long-chain polylactosamine, which influences the regulation of the immune response, making it an attractive target for immunomodulation. In the development of amide containing B3GNT2 inhibitors guided by structure-based drug design, imidazolones were found to successfully serve as amide bioisosteres. This novel imidazolone isosteric strategy alleviated torsional strain of the amide bond on binding to B3GNT2 and improved potency, isoform selectivity, as well as certain physicochemical and pharmacokinetic properties.
View Article and Find Full Text PDFAcute Myeloid Leukemia (AML) affects 20,000 patients in the US annually with a five-year survival rate of approximately 25%. One reason for the low survival rate is the high prevalence of clonal evolution that gives rise to heterogeneous sub-populations of leukemic cells with diverse mutation spectra, which eventually leads to disease relapse. This genetic heterogeneity drives the activation of complex signaling pathways that is reflected at the protein level.
View Article and Find Full Text PDFHepatic stellate cells (HSCs), alternatively known as liver pericytes, can differentiate into myofibroblasts and secrete extra-cellular matrix components, thereby promoting wound healing and fibrosis. Studying HSCs can provide insights into the pathological mechanisms governing these processes. HSC isolation methods typically comprise of enzymatic digestion followed by density gradient centrifugation and/or Fluorescent Activated Cell Sorting (FACS) mediated sorting.
View Article and Find Full Text PDFThe epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-β) from latent complexes via integrin-α activation. Using acute injury models in two different tissues, we found that by inducing TGF-β activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue.
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