A5039974711- Congenital heart defects research
- Congenital gastrointestinal and neural anomalies
- Multiple Myeloma Research and Treatments
- Congenital Heart Disease Studies
- Wnt/β-catenin signaling in development and cancer
- Chronic Lymphocytic Leukemia Research
- Axon Guidance and Neuronal Signaling
- Lymphoma Diagnosis and Treatment
- Chemical Reactions and Isotopes
- Cancer-related gene regulation
- Liver Disease Diagnosis and Treatment
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Hippo pathway signaling and YAP/TAZ
- Digestive system and related health
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Neurogenesis and neuroplasticity mechanisms
- Tissue Engineering and Regenerative Medicine
- Immune Cell Function and Interaction
- Pancreatitis Pathology and Treatment
- Galectins and Cancer Biology
- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
Dana-Farber Cancer Institute
2019-2022
Harvard University
2019-2022
University of Liverpool
2017-2021
University of Bristol
2014
Metastatic prostate cancer cells display EphB receptor-mediated attraction when they contact stromal fibroblasts but EphA-driven repulsion one another. The impact of these 'social' interactions between during cell invasion and the signalling mechanisms downstream Eph receptors are unclear. Here we show that EphA regulate dissemination in a 2D dispersal assay 3D spheroid assay. We signal via exchange factor Vav2 to activate RhoA both required for cell-cell repulsion. Furthermore, find...
Abstract Colorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator Wnt/β-catenin pathway, plays critical roles CRC pathogenesis. Here we have identified β-catenin-independent function BCL9 poor-prognosis subtype tumors characterized by expression stromal and neural associated genes. In...
Dysregulated Wnt/β-catenin signaling is implicated in the pathogenesis of many human cancers, including colorectal cancer (CRC), making it an attractive clinical target. With aim inhibiting oncogenic Wnt activity, we developed a high-throughput screening AlphaScreen assay to identify selective small-molecule inhibitors interaction between β-catenin and its coactivator BCL9. We identified compound that consistently bound specifically inhibited vivo native β-catenin/BCL9 complex formation CRC...
MYD88 L265P is the most common mutation in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and one of frequent poor-prognosis subtypes diffuse large B-cell lymphoma (DLBCL). Although inhibition mutated pathway has an adverse impact on LPL/WM DLBCL cell survival, its role initiation remains to be clarified. We show that mice, human MYD88L265P promotes development a non-clonal, low-grade lymphoproliferative disorder with several clinicopathologic features resemble LPL/WM,...
Acute pancreatitis is a frequent disease that lacks specific drug treatment. Unravelling the molecular mechanisms of acute essential for development new therapeutics. Several inducers trigger sustained Ca2+ increases in cytosol and mitochondria pancreatic acinar cells. The mitochondrial calcium uniporter (MCU) mediates uptake regulates bioenergetics plays an important role cell survival, damage death. Aberrant signaling cells have been implicated initiation pancreatitis. primary aim this...
F1F0-ATP synthase inhibitory factor 1 (IF1) inhibits the reverse mode of synthase, and therefore protects cellular ATP content at expense accelerated loss mitochondrial membrane potential (ΔΨm). There is considerable variability in IF1 expression its influence on bioenergetics between different cell types. High levels a number cancers have been linked to increased glycolysis, resistance death, migration proliferation. However, neither nor role normal pancreas or pancreatic cancer has...
Abstract Previously, genetic lineage tracing based on the mesothelial marker Wt1, appeared to show that peritoneal cells have a range of differentiative capacities and are direct progenitors vascular smooth muscle in intestine. However, it was not clear whether this temporally limited process or continued throughout postnatal life. Here, using conditional Wt1 -based approach, we demonstrate adult peritoneum covering intestine, mesentery body wall only maintained itself failed contribute...
Abstract Previously, genetic lineage tracing based on the mesothelial marker Wt1, appeared to show that peritoneal cells have a range of differentiative capacities and are direct progenitors vascular smooth muscle in intestine. However, it was not clear whether this temporally limited process or continued throughout postnatal life. Here, using conditional Wt1-based approach, we demonstrate adult peritoneum covering intestine, mesentery body wall only maintained itself failed contribute other...