A5049405375- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Viral-associated cancers and disorders
- DNA Repair Mechanisms
- CAR-T cell therapy research
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Acute Lymphoblastic Leukemia research
- PARP inhibition in cancer therapy
- CNS Lymphoma Diagnosis and Treatment
- BRCA gene mutations in cancer
- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related gene regulation
- RNA Research and Splicing
- Fluid Dynamics and Thin Films
- Immunotherapy and Immune Responses
- Lipid Membrane Structure and Behavior
- Advanced Breast Cancer Therapies
- Immune Cell Function and Interaction
- Advanced Radiotherapy Techniques
- Gene expression and cancer classification
- Genomic variations and chromosomal abnormalities
Josep Carreras Leukaemia Research Institute
2020-2023
Institute of Molecular Biology and Biophysics
2023
Institute for Biomedicine
2023
Memorial Sloan Kettering Cancer Center
2016-2019
Cornell University
2012-2018
Max Planck Institute of Colloids and Interfaces
2006-2010
Universidad de Zaragoza
2003
Tumors with mismatch repair deficiency (MMR-d) are characterized by sequence alterations in microsatellites and can accumulate thousands of mutations. This high mutational burden renders tumors immunogenic sensitive to programmed cell death-1 (PD-1) immune checkpoint inhibitors. Yet, despite their tumor immunogenicity, patients MMR-deficient experience highly variable responses, roughly half refractory treatment. We present experimental clinical evidence showing that the degree...
Despite the unprecedented clinical activity of Bruton tyrosine kinase (BTK) inhibitor ibrutinib in mantle cell lymphoma (MCL), acquired resistance is common. By longitudinal integrative whole-exome and whole-transcriptome sequencing targeted sequencing, we identified first relapse-specific C481S mutation at binding site BTK MCL cells progression following a durable response. This enhanced AKT activation tissue-specific proliferation resistant driven by CDK4 activation. It was absent,...
BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair germ-line cancer pre-disposition genes that result a syndrome of hereditary breast ovarian (HBOC). Whether or somatic alterations these other members the HR pathway if mono- bi-allelic HR-related have phenotypic impact on cancers remains to be fully elucidated. Here, we perform pan-cancer analysis The Cancer Genome Atlas (TCGA) data set observe pathogenic repair-related prevalent across many malignancies. These often...
Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative harbor highly recurrent codon Q61 HRAS hotspot which co-occur with PIK3R1 mutations. In two- three-dimensional cell culture models,...
Abstract Granular cell tumors (GCTs) are rare that can arise in multiple anatomical locations, and characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs currently unknown. Here, we apply whole-exome sequencing targeted analysis to reveal mutually exclusive, clonal, inactivating somatic mutations the endosomal pH regulators ATP6AP1 or ATP6AP2 72% GCTs. Silencing these genes vitro results impaired vesicle acidification, redistribution compartments, accumulation...
Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays role DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics landscape of somatic genetic alterations 24 BCs from ATM mutation carriers by whole-exome targeted sequencing. ATM-associated were consistently hormone receptor positive largely displayed minimal immune infiltrate. Although 79.2% these tumors exhibited loss...
Significance Cancers associated with the human papillomavirus, including oropharyngeal, anal canal, cervical, and vulvar carcinomas, constitute about 4.5% of all solid tumors. In many cases, they can be readily cured radiotherapy, which is mainstay treatment. HPV-associated cancers are more radiosensitive than HPV-negative cancers, but mechanism this radiosensitivity unknown. Across oncology, HPV association one only validated molecular biomarker radiosensitivity. Here, we demonstrate that...
Homologous recombination (HR) DNA repair-deficient (HRD) breast cancers have been shown to be sensitive repair targeted therapies. Burgeoning evidence suggests that sporadic cancers, lacking germline BRCA1/BRCA2 mutations, may also HRD. We developed a functional ex vivo RAD51-based test identify HRD primary cancers. An integrated approach examining methylation, gene expression, and whole-exome sequencing was employed ascertain the aetiology of Functional displayed genomic features lack...
Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk breast cancer development, consistent with role PALB2 homologous recombination (HR) DNA repair. Here, we sought define repertoire somatic genetic alterations PALB2-associated cancers (BCs), and whether BCs display bi-allelic inactivation and/or genomic features HR-deficiency (HRD). Twenty-four patients mutations were analyzed by whole-exome sequencing (WES, n = 16) or...
Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study cell-intrinsic lung (LC) to interferon-γ (IFNγ), a cytokine promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness IFNγ subset LCs as result JAK2 or IFNGR1 inactivation. A submaximal affects another shows constitutive low levels IFNγ-stimulated genes (IγSGs) coupled...
Recent successes in the crystallographic determination of structures transmembrane proteins G protein-coupled receptor (GPCR) family have established lipidic cubic phase (LCP) environment as medium choice for growing structure-grade crystals by method termed "in meso". The understanding meso crystallogenesis is currently at a descriptive level. To enable an eventual quantitative, energy-based description nucleation and crystallization mechanism, we examined properties system dynamics GPCR...
BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show curvature sensing (MCS) directs cellular localization function of the domain PICK1. In PICK1, homologous proteins ICA69 arfaptin2, identify an amphipathic helix N-terminal to mediates MCS. Mutational disruption in PICK1 impaired MCS without affecting binding per se. insulin-producing INS-1E cells, super-resolution microscopy revealed selectively compromised density on insulin...
// Jennifer Ma 1 , Jeremy Setton Luc Morris 2 Pedro Blecua Carrillo Albornoz Christopher Barker Benjamin H. Lok Eric Sherman 3 Nora Katabi 4 Kathryn Beal Ian Ganly Simon N. Powell Nancy Lee Timothy A. Chan 1, 5 Nadeem Riaz Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA Surgery, Medical Pathology, Human Oncology and Pathogenesis, Correspondence to: Riaz, email: riazn@mskcc.org Chan, chant@mskcc.org Keywords: somatic ATM mutations, radiation therapy...
We study the morphologies of single liquid droplets wetting a substrate in presence line tension three-phase contact line. On homogeneous substrate, leads to discontinuous unbinding droplet if its volume is decreased below critical value. For structured surface with circular domain, contrast gives rise depinning transitions from domain boundary as varied. calculate corresponding free energy bifurcation diagram analytically for axisymmetric shapes. Numerical minimization shows that contrasts...
Abstract Purpose: Despite the remarkable activity of BTK inhibitors (BTKi) in relapsed B-cell non–Hodgkin lymphoma (B-NHL), no clinically-relevant biomarker has been associated to these agents so far. The relevance phosphoproteomic profiling for early identification BTKi responders remains underexplored. Experimental Design: A set six clinical samples from an ongoing phase I trial dosing patients with chronic lymphocytic leukemia (CLL) TG-1701, a novel irreversible and highly specific BTKi,...
Immunotherapy-based regimens have considerably improved the survival rate of B-cell non-Hodgkin lymphoma (B-NHL) patients in last decades; however, most disease subtypes remain almost incurable. TG-1801, a bispecific antibody that targets CD47 selectively on CD19+ B-cells, is under clinical evaluation relapsed/refractory (R/R) B-NHL either as single-agent or combination with ublituximab, new generation CD20 antibody. A set eight cell lines and primary samples were cultured vitro presence...
We studied the process of thinning thin liquid films stabilized with nonionic surfactant n-dodecyl-β-maltoside (β-C12G2) primary interest in interfacial diffusion processes during dependent on concentration. The concentration film forming solutions was varied from 0.01 to 1.0 mM through critical micellar 0.16 at constant electrolyte (NaCl) concentration, nominally 0.2 M. This assures formation Newton black end process. velocity analyzed combining previously developed theoretical approaches....
We study morphological transitions of droplets on a structured substrate containing two circular lyophilic domains for arbitrary domain and wettabilities. derive the stability criterion that at least one must be pinned boundary with contact angle smaller than π/2. This determines seven classes stable or metastable droplet morphologies system. present complete classification metastability these as function three control parameters provided by total volume, wettability, wettability. find...
Homologous recombination (HR) enables precise DNA repair after double strand breaks (DSBs) using identical sequence templates, whereas homeologous (HeR) uses only partially homologous sequences. Homeologous introduces mutations through gene conversion and genomic deletions single-strand annealing (SSA). mismatch (MMR) inhibits HeR, but the roles of mammalian MMR MutL homologues (MLH1, PMS2 MLH3) proteins in HeR suppression are poorly characterized. Here, we demonstrate that mouse embryonic...