- Sirtuins and Resveratrol in Medicine
- Receptor Mechanisms and Signaling
- Ubiquitin and proteasome pathways
- Nicotinic Acetylcholine Receptors Study
- Chronic Lymphocytic Leukemia Research
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Genetic factors in colorectal cancer
- Tea Polyphenols and Effects
- Collagen: Extraction and Characterization
- Lymphoma Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Biochemical effects in animals
- Analytical Chemistry and Chromatography
- Molecular Biology Techniques and Applications
- Genomics and Phylogenetic Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Retinal Development and Disorders
- Digital Filter Design and Implementation
- Cardiomyopathy and Myosin Studies
- Heart Failure Treatment and Management
- Numerical Methods and Algorithms
Leidos (United States)
2015-2020
Frederick National Laboratory for Cancer Research
2013-2020
National Cancer Institute
2004-2018
Leidos Biomedical Research Inc. (United States)
2016-2018
Computing Center
2016
Science Applications International Corporation (United States)
2005-2014
United States Department of Health and Human Services
2014
Salus University
2008
National Institute on Aging
2004-2007
National Institutes of Health
2004-2007
Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this is co-opted into contributing toward tumor growth instead preventing its progression. We seek to reestablish an antitumor by selectively targeting surface receptors and endogenous signaling processes macrophage subtypes driving cancer RP-182 synthetic 10-mer amphipathic analog host defense peptides that induces conformational switch mannose receptor CD206...
Background Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk distant metastasis at every disease stage. We aimed to characterize genomic landscape LUAD identify mutation signatures associated with tumor progression. Methods Findings performed an integrative analysis, incorporating whole exome sequencing (WES), determination DNA copy number methylation, transcriptome for 101 samples from Environment And Genetics in Etiology (EAGLE) study....
Abstract Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, report clonal shifts (change >0.1 cancer cell fraction, Q < 0.1) 31% patients during first year therapy, associated with adverse outcome. We also observe transcriptional downregulation pathways mediating energy metabolism,...
Flavonoids are polyphenolic secondary metabolites synthesized by plants and fungus with various pharmacological effects. Due to their plethora of biological activities, they have been studied extensively in drug development. They shown modulate the activity a NAD
For unknown reasons, there is huge variability in risk conferred by different HPV types and, remarkably, strong differences even between closely related variant lineages within each type. HPV16 a uniquely powerful carcinogenic type, causing approximately half of cervical cancer and most other HPV-related cancers. To permit the large-scale study genome precancer/cancer, starting with cancer, we developed high-throughput next-generation sequencing (NGS) whole-genome method. We designed custom...
The cytokine subunit p19 signals alone and intracellularly to promote inflammation in endothelial cells.
Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with originally seen at NIH 1969. used whole exome sequencing study this family, conducted silico bioinformatics analysis, protein structural modeling laboratory experiments assess the impact of identified CEBPA Q311P mutation. Unlike most previously CEBPA, which were N-terminal frameshift mutations, we novel variant that was...
Hereditary diffuse gastric cancer (HDGC) is a syndrome associated with variants in E-cadherin (CDH1), and lobular breast cancer. There considerable heterogeneity its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status phenotypes of HDGC.
Hodgkin lymphoma shows strong familial aggregation but no major susceptibility genes have been identified to date. The goal of this study was identify high-penetrance variants using whole exome sequencing in 17 prone families with three or more affected cases obligate carriers (69 individuals), followed by targeted an additional 48 smaller HL (80 individuals). Alignment and variant calling were performed standard methods. Dominantly segregating, rare, coding potentially functional further...
A large number of drug substances act as noncompetitive inhibitors (NCIs) the nicotinic acetylcholine receptor (nAChR) by blocking ion flux through channel. An affinity chromatography technique has been developed for investigating interactions between NCIs and α3β4 subtype neuronal nAChR. The data obtained from chromatographic study were used to construct QSAR models NCI−nAChR binding with both electronic steric parameters observed important descriptors. molecular model transmembrane domain...
Background and purpose: The human organic cation transporter‐1 (hOCT1) is a polyspecific transporter that plays role in drug distribution, metabolism excretion. Previous studies have demonstrated hOCT1 binding can be stereoselective, but the mechanism for stereochemical recognition has not been described. purpose of this study was to develop pharmacophore model describe stereoselective hOCT1. Experimental approach: A set 22 compounds including 8 pairs enantiomers five diastereomers used...
ROS-GC1 membrane guanylate cyclase is a Ca2+ bimodal signal transduction switch. It turned "off" by rise in free from nanomolar to the semicromolar range photoreceptor outer segments and olfactory bulb neurons; similar bipolar ganglion retinal neurons it "on". These opposite operational modes of switch are specified its sensing devices, respectively termed GCAPs CD-GCAPs. Neurocalcin δ CD-GCAP. In present study, neurocalcin δ-modulated site, V837−L858, has been mapped. The location...
Abstract Summary: As sequencing becomes cheaper and more widely available, there is a greater need to quickly effectively analyze large-scale genomic data. While the functionality of AVIA v1.0, whose implementation was based on ANNOVAR, comparable with other annotation web servers, v2.0 represents an enhanced web-based server that extends annotations cell-specific transcripts protein-level functional annotations. With AVIA’s improved interface, users can better visualize their data, perform...
A molecular model of the α3β2 nAChR lumen channel was constructed and hydrophobic clefts were observed near receptor gate. Docking simulations indicated that ligand−nAChR complexes formed by interactions with cleft hydrogen bond interactions. The equilibrium constants association dissociation constant rates associated binding determined using nonlinear chromatography on an immobilized column. computational-chromatography approach can be used to predict describe