< GPCR News < GPCRs in Oncology and Immunology Functional Assessment of Cancer-Linked Mutations in Sensitive Intolerant and tolerant-control residues that overlap with pathogenic cancer mutations reported in the Identified intolerant residues with reported cancer-linked mutations RGS14-R173C/H and RGS4-K125Q/E126K , including cancer-linked mutations in regulator of G protein signaling (RGS) proteins. We found that 3DMTR more accurately classifies loss-of-function mutations in RGS proteins than other

< GPCR News < GPCRs in Oncology and Immunology Mutation Patterns Predict Drug Sensitivity in Acute Myeloid We also integrated large public datasets to understand the co-occurring mutation patterns and further investigated the mutation profiles in the single cells. to some drug classes, such as MEK inhibitors for RAS-mutated leukemia. It provides a framework for categorizing patients with AML by mutations that enable drug sensitivity

< GPCR News < GPCRs in Oncology and Immunology The Effect of Cancer-Associated Mutations on Ligand Binding In this study, we aimed to investigate the effects of cancer patient-derived 5-HT2C receptor mutations By filtering the sequencing data from the Genomic Data Commons data portal (GDC), we selected 12 mutations These two mutations may disrupt the conserved ionic interaction between E6.30 and R3.50, and thus increase Such mutations may affect serotonin-mediated signaling in tumor cells as well as treatment strategies

< GPCR News < GPCRs in Oncology and Immunology Pan-cancer functional analysis of somatic mutations in Here we used a dataset of mutations found in patient samples derived from the Genomic Data Commons and We explored cancer-related mutation patterns in all GPCR classes combined and individually. While the location of the mutations across the protein domains did not differ significantly in the two datasets, a mutation enrichment in cancer patients was observed among class-specific conserved motifs

Oncology and Immunology Ultrasensitive dose-response for asbestos cancer risk implied by new inflammation-mutation asbestos) fibers in humans and experimental animals are thought to involve modes of action driven by mutations A recent Inflammation Somatic Mutation (ISM) theory of cancer posits instead that tissue-damage-associated promote cancer, but rather is a requisite co-initiator (acting together with as few as two somatic mutations Author Kenneth T Bogen Tags Asbestos , Cytotoxicity , Inflammation , Lung cancer , Mesothelioma , Mutation

One promising potential application of such mathematical models is the study of how disease-causing mutations develop a mechanistic mathematical model of a G-protein coupled receptor signaling network that is mutated Modeling the two major, mutually-exclusive, oncogenic mutations (Gαq/11 and CysLT2R) revealed the potential This led us to hypothesize that CYSLTR2 mutations in UM must co-occur with other mutations to activate FAK/YAP/TAZ signaling, and our bioinformatic analysis uncovers a role for co-occurring mutations involving

< GPCR News < GPCRs in Oncology and Immunology Spliceosome mutations are associated with clinical response The gene signature was evaluated in independent datasets and used to identify associated mutated genes In the phase 1b/2 trial, patients with SF mutations (SRSF2, SF3B1) had a higher CR/CRi rate (50%) compared to those without SF mutations (9%). a potential therapy in R/R AML patients, particularly those with high OXPHOS gene expression and SF mutations

nature of PBMAH and familial aggregation, led to the identification of germline heterozygous inactivating mutations the ARMC5 gene, in 20-25% of the apparent sporadic cases and more frequently in familial cases; ARMC5 mutations More recently, combined germline mutations/pathogenic variants and somatic events inactivating the KDM1A

Gene ontology analysis was performed for differentially expressed proteins between wild-type and mutant The results suggested that GNAS mutations impact endocrinological features in acromegaly through GPCR These results identified a biological connection between GNAS mutations and the clinical and biochemical

Zozaya "My doctoral research was focused on investigating the cellular effects of missense lung cancer-mutations

CXCR4 only responds to wild-type CXCL12 and is sensitive to mutation of the chemokine. responds to CXCL12, CXCL12 variants, other peptides and proteins, and is relatively insensitive to mutation

used with 7 + 3 in adults with newly-diagnosed acute myeloid leukemia (AML), irrespective of the FLT3-mutation 80% and 76%, without differences in MRD- CR rates, OS, or EFS between patients with or without FLT3-mutated

Mutations in aGPCRs have been linked to various neuropsychiatric phenotypes, and my work will provide

We examined the prenylation of carboxy-terminus (Ct) mutated Gγ in cells exposed to Fluvastatin and prenyl inhibitors and monitored the subcellular localization of fluorescently tagged Gγ subunits and their mutants

The adapter protein 3BP2 is mutated in Cherubism.

This is a rare neurodevelopmental disorder caused by de novo mutations in the GRIN genes that encode

Although BCR-ABL1 mutation is a key cause of CML resistance, understanding mechanisms independent of

Randy’s lab has a special interest in studying disease-associated mutations to human GPCRs that perturb

dysplasia (FD) of the bone is characterized by fibrotic, expansile bone lesions caused by activating mutations

2012 from the University of Oxford, where her research focused on the cellular mechanisms by which mutations

Abstract "Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome caused by a germline mutation Glioblastoma (GBM) is the most prevalent central nervous system tumor in LFS, with TP53 mutations detected that ADGRB3 functions as a tumor suppressor in the brain, and its silencing, in the context of p53 mutation flexibility of GAIN flaps affects aGPCR function under native conditions, we strategically inserted specific mutations

analysis of cancer drivers by co-developing GECCO, an algorithm for the identification of noncoding mutations He highlighted their interest in non-coding mutations in promoters and the 3'UTR region important for

cancers, BAI1-3 expression can be lost through epigenetic silencing, copy number loss or truncating mutations WNT pathway activation in WNT-MB is driven by mutations of the CTNNB1 gene, activating ß-catenin-dependent GAIN-targeted antibodies, and cancer-associated mutations at the GAIN-7TM interface, alter holoreceptor

During that time, I investigated the effect of lung cancer-related mutations in the GAIN domain of the

Zozaya "My doctoral research was focused on investigating the cellular effects of missense lung cancer-mutations biochemical and cell-biological approaches using cell-lines overexpressing wild-type and N-glycosylation mutants

Mutational experiments on residues of interest showed that restoring the Phe-His interaction in the uncleaving

GPCR Podcast << Back to podcast list Murat Tunaboylu & Ben Holland About Murat Tunaboylu "Murat Tunaboylu After switching to biotech, Murat has built cell imaging software and lab robots to accelerate cancer Murat Tunaboylu on the web Antiverse DSV Future of Drug Discovery Podcast Twist Bioscience LinkedIn Twitter

< GPCR News < GPCRs in Oncology and Immunology Intermediate-state-trapped mutants pinpoint G protein-coupled demonstrate the feasibility of enriching the populations of discrete states via conformation-biased mutants These mutants adopt distinct distributions among five states that lie along the activation pathway of Intermediate-state-trapped mutants will also provide useful information in relation to receptor-G protein