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- | Journal: Wiskott-Aldrich syndrome protein maintains regulatory T cell tolerance by modulating their surface IL-2 receptor levels. (Pubmed Central) - Nov 18, 2024
Consistently, N-WASP inhibition in Tregs using wiskostatin reduced IL-2R internalization. Together, our results reveal a novel intrinsic role of WASP in regulation of surface IL-2R dynamics in Tregs, highlighting a potential new therapeutic approach for autoimmune diseases.
- | EG-011 / E2DG, Oncology Institute of Southern Switzerland
Journal: A first-in-class Wiskott-Aldrich syndrome protein activator with anti-tumor activity in hematologic cancers. (Pubmed Central) - Nov 4, 2024
Here, we describe the development of EG-011, a first-in-class small molecule activator of the autoinhibited form of WASp...Actin polymerization and WASp binding was demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs-inducing actin polymerization.
- | Journal: Controlled WASp activity regulates the proliferative response for Treg cell differentiation in the thymus. (Pubmed Central) - May 7, 2024
Conversely, XLN CD4 single-positive thymocytes efficiently differentiate into Foxp3+ Treg cells following a high proliferative response to IL-2 and TGF-?, associated with high CD25 expression when compared with WT cells. Altogether, these results show that specific mutations of WASp affect Treg cell development differently, demonstrating a critical role of WASp activity in supporting Treg cell development and expansion.
- | Journal: N-WASP-dependent branched actin polymerization attenuates B-cell receptor signaling by increasing the molecular density of receptor clusters. (Pubmed Central) - Dec 17, 2023
These results suggest that N-WASP-activated Arp2/3, coordinating with myosin, generates centripetally moving foci and contractile actomyosin ring-like structures from lamellipodial networks, enabling contraction. B-cell contraction attenuates BCR signaling by pushing out both stimulatory kinases and inhibitory phosphatases from BCR clusters, providing novel insights into actin-facilitated signal attenuation.
- | Journal: Caterpillars (Manduca sexta) parasitized by the wasp Cotesia congregata stop chewing despite an intact motor system. (Pubmed Central) - Aug 3, 2023
The same result was observed in unparasitized caterpillars given the same treatment. Our results suggest that the reduced feeding in parasitized caterpillars was not due to damage to the central pattern generator (CPG) for chewing, motor nerves or chewing muscles, but was more likely due to a suppression of chewing CPG activity by ascending or descending inputs.
- | Journal: Chlamydia trachomatis TmeB antagonizes actin polymerization via direct interference with Arp2/3 activity. (Pubmed Central) - Jul 28, 2023
In aggregate, these data point to opposing functions for TmeA and TmeB that manifest during the invasion process. These studies raise intriguing questions regarding the dynamic interplay between TmeA, TmeB, and branched actin polymerization during chlamydial entry.
- EG-011 / E2DG, Oncology Institute of Southern Switzerland
The first-in-class WASP activator EG-011 is active in lymphoma and multiple myeloma cell lines resistant to FDA approved compounds (Exhibition Hall) - Sep 3, 2022 - Abstract #AACRNCIEORTC2022AACR_NCI_EORTC_436;
Conclusions. These data indicate that the first-in-class WASP activator EG-011 was active also after acquisition of resistance to different FDA approved agents such as PI3K, BTK and proteasome inhibitors in MZL and MM models.