A5023777752- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Fungal and yeast genetics research
- RNA regulation and disease
- RNA Research and Splicing
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Genomics and Chromatin Dynamics
- Fermentation and Sensory Analysis
- Acute Myeloid Leukemia Research
- Genetic diversity and population structure
- Genetic Mapping and Diversity in Plants and Animals
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Lymphoma Diagnosis and Treatment
- Pulmonary Hypertension Research and Treatments
- Nuclear Receptors and Signaling
- Bladder and Urothelial Cancer Treatments
- Molecular Biology Techniques and Applications
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Evolution and Genetic Dynamics
Enzo Life Sciences (United States)
2022-2023
Foundation Medicine (United States)
2017-2019
Editas Medicine (United States)
2018
University of Massachusetts Chan Medical School
2017
University of Washington
2009-2014
High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown be more significantly associated with response PD-1 PD-L1 blockade immunotherapy than or expression, as measured by immunohistochemistry (IHC). The distribution TMB the subset patients high not well characterized in majority cancer types. In this study, we compare a targeted comprehensive genomic profiling (CGP) assay exome sequencing simulate expected variance when...
The size, shape, and behavior of the modern domesticated dog has been sculpted by artificial selection for at least 14,000 years. genetic substrates selective breeding, however, remain largely unknown. Here, we describe a genome-wide scan in 275 dogs from 10 phenotypically diverse breeds that were genotyped over 21,000 autosomal SNPs. We identified 155 genomic regions possess strong signatures recent contain candidate genes phenotypes vary most conspicuously among breeds, including coat...
Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), 2 (PDCD1LG2 PDL2), and Janus kinase (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting high response rates to (PD-1)/programmed (PD-L1) blockade. The prevalence utility of PDL1 amplification as a biomarker PD-1/PD-L1 blockade are unknown other tumors.To examine the its solid tumors.This retrospective study (October 1, 2012, October 2017) used deidentified tumor database from commercial company...
Abstract Colorectal cancer (CRC) is increasingly appreciated as a heterogeneous disease, with factors such microsatellite instability (MSI), subsite within the colon versus rectum, and age of diagnosis associated specific disease course therapeutic response. Activating oncogenic mutations in KRAS NRAS are common CRC, driving tumor progression influencing efficacy both cytotoxic targeted therapies. The RAS mutational spectrum differs substantially between tumors arising from distinct tissues....
Abstract Purpose: The incidence rates of colorectal cancers are increasing in young adults. objective this study was to investigate genomic differences between tumor samples collected from younger and older patients with cancer. Experimental Design: DNA extracted 18,218 clinical specimens, followed by hybridization capture 3,769 exons 403 cancer-related genes 47 introns 19 commonly rearranged Genomic alterations (GA) were determined, association patient age microsatellite...
To better understand the quantitative characteristics and structure of phenotypic diversity, we measured over 14,000 transcript, protein, metabolite, morphological traits in 22 genetically diverse strains Saccharomyces cerevisiae . More than 50% all varied significantly across [false discovery rate (FDR) = 5%]. The correlations is complex, with 85% correlated at least one other phenotype (median 6, maximum 328). We show how high-dimensional molecular phenomics data sets can be leveraged to...
Abstract Aim Characterize Growth Differentiation Factor 15 (GDF15) as a secreted biomarker of the integrated stress response (ISR) within central nervous system (CNS). Methods We determined GDF15 levels utilizing in vitro and vivo neuronal systems wherein ISR was activated. Primarily, we used murine model vanishing white matter disease (VWMD), neurological driven by persistent CNS, to establish link between cerebrospinal fluid (CSF) gene expression signature CNS. also CSF VWM patients....
Advances in sequencing technology have enabled whole-genome sequences to be obtained from multiple individuals within species, particularly model organisms with compact genomes. For example, 36 genome of Saccharomyces cerevisiae are now publicly available, and SNP data available for even larger collections strains. One potential use these resources is mapping the genetic basis phenotypic variation through genome-wide association (GWA) studies, benefit that associated variants can studied...
• Here, we investigated the genetic underpinnings of pollination-related floral phenotypes in Thalictrum, a ranunculid with apetalous flowers. The variable presence petaloid features other organs correlates distinct adaptations to insect vs. wind pollination. Conical cells are present sepals or stamens insect-pollinated species, and stigmas. We characterized Thalictrum ortholog Antirrhinum majus transcription factor MIXTA-like2, responsible for conical cells, from three species morphologies,...
Mutations in the human gene ALMS1 result Alström Syndrome, which presents with early childhood obesity and insulin resistance leading to Type 2 diabetes. Previous genomewide scans for selection HapMap data based on linkage disequilibrium population structure suggest that was subject recent positive selection. Through a detailed genomic analysis of existing sets new resequencing obtained geographically diverse populations, we find signature at is considerably more complex than what would be...
Chromatin accessibility is an important functional genomics phenotype that influences transcription factor binding and gene expression. Genome-scale technologies allow chromatin to be mapped with high-resolution, facilitating detailed analyses into the genetic architecture evolution of structure within between species. We performed Formaldehyde-Assisted Isolation Regulatory Elements sequencing (FAIRE-Seq) map in two parental haploid yeast species, Saccharomyces cerevisiae paradoxus their...
The repeating subunit of chromatin, the nucleosome, includes two copies each four core histones, and several recent studies have reported that asymmetrically-modified nucleosomes occur at regulatory elements in vivo. To probe mechanisms by which histone modifications are read out, we designed an obligate pair H3 heterodimers, termed H3X H3Y, extensively validated genetically biochemically. Comparing effects asymmetric tail point mutants with those symmetric double revealed a single...
Abstract Background. Cancer gene mutations exhibit mutation patterns of prevalence that vary across different ancestry groups. For example, EGFR variants are more frequent in non-small cell lung cancer among people with Asian ancestry, and KRAS observed frequently colorectal patients African American ancestry. Additionally, many histological subtypes cancers demonstrate differences between However, studies lack the statistical power to identify such nuances. The large cohort who have...
Introns are a ubiquitous feature of eukaryotic genomes, and the dynamics intron evolution between species has been extensively studied. However, comparatively few analyses have focused on evolutionary forces shaping patterns variation within species. To better understand population genetic characteristics introns, we performed an extensive genetics analysis key splice sequences obtained from 38 strains Saccharomyces cerevisiae. As expected, found that purifying selection is dominant force...
Abstract Background The frequency of targetable somatic genomic alterations is known to differ based on a patient's ancestry; for example, in lung adenocarcinoma EGFR mutations are more common East Asians than Europeans. Accurately characterizing these differences will help illuminate the genetic etiology cancer between populations. Methods We inferred estimated population ancestry 100,000 de-identified patients from comprehensive profiling (CGP) tumor specimens assessed course routine...
Noncoding genetic variation is known to significantly influence gene expression levels in a growing number of specific cases; however, the patterns genome-wide noncoding present within populations, evolutionary forces acting on variants, and relative effects regulatory polymorphisms transcript abundance are not well characterized. Here, we address these questions by analyzing motifs for 177 DNA binding proteins 37 strains Saccharomyces cerevisiae. Between S. cerevisiae strains, found...
Considerable work has been devoted to identifying regions of the human genome that have subjected recent positive selection. Although detailed follow-up studies putatively selected are critical for a deeper understanding evolutionary history, such received comparably less attention. Recently, we shown ALMS1 target selection acting on standing variation in Eurasian populations. Here, describe careful analysis genetic across region, which unexpectedly revealed cluster substrates Specifically,...
Idiopathic pulmonary fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive extracellular matrix deposition for which unmet need persists effective therapeutics. The bioactive eicosanoid, prostaglandin F2α, its cognate receptor FPr (Ptgfr) are implicated as TGF-β1-independent signaling hub IPF. To assess this, we leveraged our published murine PF model (IER-SftpcI73T) expressing disease-associated...
3039 Background: Higher levels of tumor mutational burden (TMB) can predict sensitivity to immunotherapies (IO), which are FDA approved treat NSCLC, melanoma, and urothelial carcinoma (Ca). TMB may be a biomarker for IO, irrespective type. has not been explored widely tumors unknown primary site, but reveal additional treatment options. Methods: Comprehensive genomic profiling DNA from FFPE tissue samples was performed using hybrid-capture, next-generation sequencing. calculated by counting...