Erik Sahai

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Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases

Heike Seifert, Erik Sahai et 6 al.

Nov 3, 2015 in Pigment Cell & Melanoma Research
Here, we retrospectively review imaging of 68 consecutive unselected patients with BRAF V600‐mutant metastatic melanoma for organ‐specific response and progression on vemurafenib. Complete or partial responses were less often seen in the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%), subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%), P < 0.0...


Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts.

Fernando Calvo, Erik Sahai et 10 al.

May 26, 2013 in Nature cell biology
To learn more about cancer-associated fibroblasts (CAFs), we have isolated fibroblasts from different stages of breast cancer progression and analysed their function and gene expression. These analyses reveal that activation of the YAP transcription factor is a signature feature of CAFs. YAP function is required for CAFs to promote matrix stiffening, cancer cell invasion and angiogenesis. Remodell...

Stochastic Regulation of her1/7 Gene Expression Is the Source of Noise in the Zebrafish Somite Clock Counteracted by Notch Signalling.

Robert P Jenkins, Julian Lewis et 4 al.

Nov 20, 2015 in PLoS computational biology
The somite segmentation clock is a robust oscillator used to generate regularly-sized segments during early vertebrate embryogenesis. It has been proposed that the clocks of neighbouring cells are synchronised via inter-cellular Notch signalling, in order to overcome the effects of noisy gene expression. When Notch-dependent communication between cells fails, the clocks of individual cells operate...

Extracellular matrix anisotropy is determined by TFAP2C-dependent regulation of cell collisions.

Danielle Park, Erik Sahai et 8 al.

Oct 28, 2019 in Nature materials
The isotropic or anisotropic organization of biological extracellular matrices has important consequences for tissue function. We study emergent anisotropy using fibroblasts that generate varying degrees of matrix alignment from uniform starting conditions. This reveals that the early migratory paths of fibroblasts are correlated with subsequent matrix organization. Combined experimentation and ad...


Tissue clonality of dendritic cell subsets and emergency DCpoiesis revealed by multicolor fate mapping of DC progenitors.

Mar Cabeza-Cabrerizo et 19 al.

Mar 1, 2019 in Science immunology
Conventional dendritic cells (cDCs) are found in all tissues and play a key role in immune surveillance. They comprise two major subsets, cDC1 and cDC2, both derived from circulating precursors of cDCs (pre-cDCs), which exited the bone marrow. We show that, in the steady-state mouse, pre-cDCs entering tissues proliferate to give rise to differentiated cDCs, which themselves have residual prolifera...

Matrix feedback enables diverse higher-order patterning of the extracellular matrix.

Esther Wershof, Paul A Bates et 5 al.

Oct 28, 2019 in PLoS computational biology
The higher-order patterning of extra-cellular matrix in normal and pathological tissues has profound consequences on tissue function. Whilst studies have documented both how fibroblasts create and maintain individual matrix fibers and how cell migration is altered by the fibers they interact with, a model unifying these two aspects of tissue organization is lacking. Here we use computational model...

Quantitative Analysis Reveals that Actin and Src-Family Kinases Regulate Nuclear YAP1 and Its Export.

Nil Ege, Erik Sahai et 7 al.

Jun 27, 2018 in Cell systems
The transcriptional regulator YAP1 is critical for the pathological activation of fibroblasts. In normal fibroblasts, YAP1 is located in the cytoplasm, while in activated cancer-associated fibroblasts, it is nuclear and promotes the expression of genes required for pro-tumorigenic functions. Here, we investigate the dynamics of YAP1 shuttling in normal and activated fibroblasts, using EYFP-YAP1, q...


Parameter estimation in fluorescence recovery after photobleaching: quantitative analysis of protein binding reactions and diffusion.

Daniel E Williamson, John R King et 4 al.

Jun 15, 2021 in Journal of mathematical biology
Fluorescence recovery after photobleaching (FRAP) is a common experimental method for investigating rates of molecular redistribution in biological systems. Many mathematical models of FRAP have been developed, the purpose of which is usually the estimation of certain biological parameters such as the diffusivity and chemical reaction rates of a protein, this being accomplished by fitting the mode...


Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions.

Melda Tozluoğlu, Erik Sahai et 5 al.

Jun 23, 2013 in Nature cell biology
The molecular requirements and morphology of migrating cells can vary depending on matrix geometry; therefore, predicting the optimal migration strategy or the effect of experimental perturbation is difficult. We present a model of cell motility that encompasses actin-polymerization-based protrusions, actomyosin contractility, variable actin-plasma membrane linkage leading to membrane blebbing, ce...


Heat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer.

Oshrat Levi-Galibov et 20 al.

Dec 7, 2020 in Nature communications
In the colon, long-term exposure to chronic inflammation drives colitis-associated colon cancer (CAC) in patients with inflammatory bowel disease. While the causal and clinical links are well established, molecular understanding of how chronic inflammation leads to the development of colon cancer is lacking. Here we deconstruct the evolving microenvironment of CAC by measuring proteomic changes an...