A5091704875- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Lung Cancer Research Studies
- Lung Cancer Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Bone and Joint Diseases
- Protein Degradation and Inhibitors
- Cancer Immunotherapy and Biomarkers
- Cancer-related molecular mechanisms research
- Glioma Diagnosis and Treatment
- Genomic variations and chromosomal abnormalities
- Acute Myeloid Leukemia Research
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- Hematological disorders and diagnostics
- Peptidase Inhibition and Analysis
- Machine Learning in Bioinformatics
- RNA regulation and disease
Baylor College of Medicine
2017-2025
Children's Cancer Center
2017-2025
University of Massachusetts Chan Medical School
2024-2025
Gilead Sciences (United States)
2023
Texas Children's Hospital
2021-2022
McGill University
2020
Memorial Sloan Kettering Cancer Center
2014-2018
Rockefeller University
2014-2015
New York University
2012
Columbia University Irving Medical Center
2012
Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma, but the fraction who derive clinical benefit remains undefined. Here, we report experience 860 metastatic adenocarcinoma analyzed prospectively mutations in >300 cancer-associated genes. Potentially actionable events were stratified into one four levels based upon published or laboratory evidence that mutation question confers increased sensitivity to investigational therapies. Overall, 37.1% (319/860)...
Abstract Purpose: KRAS mutations occur in approximately 25% of patients with non–small cell lung cancer (NSCLC). Despite the uniform presence mutations, KRAS-mutant NSCLC can have a heterogeneous clinical course. As pattern co-occurring may describe different biological subsets adenocarcinoma, we explored effects on patient outcomes and response to therapy. Experimental Design: We identified advanced evaluated most common genomic alterations. Multivariate analyses were performed...
Heritable and idiopathic pulmonary arterial hypertension (PAH) are phenotypically identical associated with mutations in several genes related to transforming growth factor (TGF) beta signaling, including bone morphogenetic protein receptor type 2, activin receptor-like kinase 1, endoglin, mothers against decapentaplegic 9. Approximately 25% of heritable cases lack identifiable any these genes.
Purpose Microsatellite instability (MSI)/mismatch repair (MMR) status is increasingly important in the management of patients with cancer to predict response immune checkpoint inhibitors. We determined MSI from large-panel clinical targeted next-generation sequencing (NGS) data across various solid types. Methods The statuses 12,288 advanced cancers consecutively sequenced Memorial Sloan Kettering-Integrated Mutation Profiling Actionable Cancer Targets NGS assay were inferred by using...
To identify molecular factors that determine duration of response to EGFR tyrosine kinase inhibitors and novel mechanisms drug resistance, we molecularly profiled
P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon vivax, most prevalent species in humans outside Africa. Because cynomolgi shares many phenotypic, biological and genetic characteristics with we generated draft genome sequences for three strains performed genomic analysis comparing them vivax genome, as well third previously sequenced simian parasite, Plasmodium knowlesi. Here, show that genomes monkey malaria clade can be characterized by copy-number...
We introduce a method for simultaneous prediction of microRNA–target interactions and their mediated competitive endogenous RNA (ceRNA) interactions. Using high-throughput validation assays in breast cancer cell lines, we show that our integrative approach significantly improves on accuracy as assessed by both mRNA protein level measurements. Our biochemical support nearly 500 with evidence regulation tumors. Moreover, these constitute the most extensive platform computationally inferred...
We have identified 25 lesions involving alveolar lung parenchyma characterized by nodular proliferation of bland bilayered bronchiolar-type epithelium containing a continuous layer basal cells. These shared some histologic features with the recently described entity ciliated muconodular papillary tumor (CMPT); however, majority did not fit all diagnostic criteria in that they exhibited only focal or absent architecture, and had variable number mucinous cells, entirely lacking 1 both these...
Influenza viruses are enveloped, negative-sense single-stranded RNA covered in a dense layer of glycoproteins. Hemagglutinin (HA) accounts for 80 to 90% influenza glycoprotein and plays role host cell binding membrane fusion. While previous studies have characterized structures purified receptor-free receptor-bound HA, the effect receptor on HA organization structure virions remains unknown. Here, we used cryoelectron tomography visualize bound sialic acid mimic. Overall, did not result...
Abstract The predominant view of pluripotency regulation proposes a stable ground state with coordinated expression key transcription factors (TFs) that prohibit differentiation. Another perspective suggests more complexly regulated involving competition between multiple lineage-specifying TFs define pluripotency. These contrasting views were developed from extensive analyses in pluripotent cells vitro. An experimentally validated, genome-wide repertoire the regulatory interactions control...
Chromatin immunoprecipitation followed by sequencing of protein-bound DNA fragments (ChIP-Seq) is an effective high-throughput methodology for the identification context specific that are bound proteins in vivo. Despite significant progress bioinformatics analysis this genome-scale data, a number challenges remain as technology-dependent biases, including variable target accessibility and mappability, sequence-dependent variability, non-specific binding affinity must be accounted for. We...
9053 Background: Whether disease characteristics or outcomes for patients (pts) with EGFR-mutant lung cancers differ by co-mutations present is unknown. In order to understand the impact of co-mutations, we reviewed molecular results, course and clinical pts untreated, metastatic cancers. Methods: We identified all untreated who had targeted NGS performed from Jan 2014 Sept 2015. Molecular alterations in 341 genes were assessed. Fisher's exact log rank tests used identify associations...
9019 Background: KRAS mutations define the largest subset of oncogene-driven lung cancers (~25%). Patients with KRAS-mutant have a heterogeneous clinical course. The pattern co-occuring in other oncogenes and tumor suppressors has been hypothesized to describe different biological subsets patients adenocarcinoma. We used results routine, next-generation sequencing comprehensively concurrent genetic alterations present explore effect such on patient outcomes. Methods: identified mutant who...
Abstract Knowledge about the clonal evolution of a tumor can help to interpret function its genetic alterations by identifying initiating events and that contribute selective advantage proliferative, metastatic, drug-resistant subclones. Clonal be reconstructed from estimates relative abundance ( frequency ) subclone-specific in biopsies, which, turn, inform on composition. However, estimating these frequencies is complicated high instability characterizes many cancers. Models for suggest...
Substance use disorder is associated with accelerated disease progression in people human immunodeficiency virus (HIV; PWH). Problem opioid use, including high-dose therapy, prescription drug misuse, and abuse, high increasing the PWH population. Oxycodone a broadly prescribed both general population PWH. Here, we allowed HIV transgenic (Tg) rats wildtype (WT) littermates to intravenously self-administer oxycodone under short-access (ShA) conditions, which led moderate, stable,...
SUMMARY The determination of long non-coding RNA (lncRNA) function is a major challenge in biology with applications to basic, translational, and medical research [1–7]. Our efforts improve the accuracy lncRNA-target inference identified lncRNAs that coordinately regulate both transcriptional post-transcriptional processing their targets. Namely, these may transcription target chaperone resulting message until its translation, leading tightly coupled lncRNA abundance. analysis suggested...
Influenza viruses are enveloped, negative sense single-stranded RNA covered in a dense layer of glycoproteins. Hemagglutinin (HA) accounts for 80-90% influenza glycoprotein and plays role host cell binding membrane fusion. While previous studies have characterized structures receptor-free receptor-bound HA vitro, the effect receptor on organization structure virions remains unknown. Here, we used cryo-electron tomography (cryoET) to visualize bound sialic acid mimic. Overall, did not result...
Background: Magrolimab (Hu5F9-G4) is a monoclonal antibody that blocks CD47, an antiphagocytic “don’t eat me” signal overexpressed on tumor cells. The demethylating agent azacitidine (AZA) increases expression of prophagocytic signals the surface cells and acts synergistically with magrolimab to facilitate phagocytosis by macrophages. CD47 key negative regulator innate immunity; therapeutic blockade has potential trigger adaptive immune antitumor activity within bone marrow environment....