A5107843977- Particle physics theoretical and experimental studies
- High-Energy Particle Collisions Research
- Quantum Chromodynamics and Particle Interactions
- Receptor Mechanisms and Signaling
- Particle Detector Development and Performance
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Dark Matter and Cosmic Phenomena
- Computational Drug Discovery Methods
- Cosmology and Gravitation Theories
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Diabetes and associated disorders
- Mass Spectrometry Techniques and Applications
- Neutrino Physics Research
- Immune Cell Function and Interaction
- Diet, Metabolism, and Disease
- Metabolism, Diabetes, and Cancer
- Mesoporous Materials and Catalysis
- Cell Adhesion Molecules Research
- Mathematical Biology Tumor Growth
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Chemical Synthesis and Analysis
- Diabetes Treatment and Management
City of Hope
2015-2025
Beckman Research Institute
2014-2025
City Of Hope National Medical Center
2015-2025
A. Alikhanyan National Laboratory
2024
Institute of High Energy Physics
2013-2024
University of Antwerp
2024
Translational Research Informatics Center (Japan)
2024
Northwestern University
2017-2023
Saha Institute of Nuclear Physics
2014-2023
Deutsches Elektronen-Synchrotron DESY
2022-2023
Recently developed atomistic models of highly disordered nanoporous materials offer hope for a much more realistic description the pore morphology and topology in such materials; however, factor limiting their application has been computationally intensive characterization models, particularly determination size distribution. We report new technique fast computation distributions model from knowledge molecular coordinates. The distribution (PSD) is defined as statistical radius largest...
Mantle cell lymphoma (MCL) is a phenotypically and genetically heterogeneous malignancy in which the genetic alterations determining clinical indications are not fully understood. Here, we performed comprehensive whole-exome sequencing analysis of 152 primary samples derived from 134 MCL patients, including longitudinal 16 patients matched RNA-Seq data 48 samples. We classified into 4 robust clusters (C1-C4). C1 featured mutated immunoglobulin heavy variable (IGHV), CCND1 mutation,...
Decoy oligodeoxynucleotides (ODNs) allow targeting undruggable transcription factors, such as STAT3, but their limited potency and lack of delivery methods hampered translation. To overcome these challenges, we conjugated a STAT3-specific decoy to thalidomide, ligand cereblon in E3 ubiquitin ligase complex, generate proteolysis-targeting chimera (STAT3D
Abstract Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger absence an agonist; and naturally occurring constitutively active mutations have been implicated diseases. To gain insight into mechanistic aspects we report here 3.3 Å crystal structure active, agonist-bound neurotensin receptor (NTSR1) molecular dynamics simulations agonist-occupied ligand-free receptor. Comparison with NTSR1 variant that has little activity reveals...
ConspectusIncreasing levels of carbon dioxide in the atmosphere and growing need for energy necessitate a shift toward reliance on renewable sources utilization dioxide. Thus, producing carbonaceous fuel by electrochemical reduction has been very appealing. We have focused addressing principal challenges poor selectivity efficiency demonstrated here viable pathway efficient continuous CO2 to formate using metal-independent enzyme type dehydrogenase (FDH) derived from Candida boidinii yeast....
Multiple myeloma (MM) is characterized by an accumulation of malignant plasma cells (PCs) within the BM. The BM microenvironment supports survival and composed cellular fractions that foster development progression suppression immune response. Despite major progress in understanding biology pathophysiology MM, this disease still incurable requires aggressive treatment with significant side effects. CD84 a self-binding immunoreceptor belonging to signaling lymphocyte activation molecule...
G-protein coupled receptors (GPCRs) are allosteric membrane proteins mediating cellular signaling. GPCRs exhibit multiple inactive and active conformations, the population balance between these conformations is altered upon binding of signaling molecules (or ligands). However, nature conformational ensemble or mechanism transitions not well understood. We present a multiscale computational approach combining coarse-grained discrete sampling method with fine-grained molecular dynamics...
Significance G-protein-coupled receptors (GPCRs) are the largest class of mammalian signaling and mediate vast physiological responses. The capacity to modulate GPCR therapeutically is important for treatment various diseases, discovering new aspects receptor critical drug development. Protease-activated receptor-1 (PAR1) thrombin. Similar other GPCRs, PAR1 promiscuous couples multiple heterotrimeric G-protein subtypes in same cell. How a single can couple concurrently has remained an...
G-protein-coupled receptors (GPCRs) mediate multiple signaling pathways in the cell, depending on agonist that activates receptor and cellular factors. Agonists show higher potency to specific over others are known as "biased agonists" have been shown better therapeutic index. Although biased agonists desirable, their design poses several challenges date. The number of assays identify seems expensive tedious. Therefore, computational methods can reliably calculate possible bias various...
G protein–coupled receptors engage both proteins and β-arrestins, their coupling can be biased by ligands mutations. Here, to resolve structural elements mechanisms underlying effector the angiotensin II (AngII) type 1 receptor (AT1R), we combined alanine scanning mutagenesis of entire sequence with pharmacological profiling Gα q β-arrestin engagement mutant molecular dynamics simulations. We showed that AT1R involved a large number residues spread across receptor, whereas fewer regions...
The molecular and functional heterogeneity of pancreatic β-cells is well recognized, but the underlying mechanisms remain unclear. Pancreatic islets harbor a subset that co-express tyrosine hydroxylase (TH), an enzyme involved in synthesis catecholamines repress insulin secretion. Restriction TH+ within essential for appropriate function mice, such higher proportion these cells corresponds to reduced Here, we use as model dissect developmental control β-cell heterogeneity. We define specific...
Translational research in medicine, defined as the transfer of knowledge and discovery from basic sciences to clinic, is typically achieved through interactions between members across scientific disciplines overcome traditional silos within community. Thus, translational medicine underscores 'Team Medicine', partnership science researchers clinicians focused on addressing a specific goal medicine. Here, we highlight this concept City Hope perspective. Using cisplatin resistance non-small...
Abstract Aims/hypothesis Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of make distinct contributions to overall control insulin secretion. These include subpopulation highly connected ‘hub’ cells, important for propagation intercellular Ca 2+ waves. Functional subpopulations have also been demonstrated in human beta with an altered subtype distribution apparent type 2 diabetes. At present, molecular mechanisms through which cell...
The active state conformation of a G-protein coupled receptor (GPCR) is influenced by the chemical structure and efficacy bound ligand. Insight into as well activation pathway for ligands with different efficacies critical in designing functionally specific drugs GPCRs. Starting from crystal beta2-adrenergic receptor, we have used coarse grain computational methods to understand modulation potential energy landscape two full agonists, partial an inverse agonist. Our method involves...
Stability of detergent-solubilized G-protein-coupled receptors (GPCRs) is crucial for their purification in a biologically relevant state, and it well-known that short chain detergents such as octylglucoside are more denaturing than long dodecylmaltoside. However, the molecular basis this phenomenon poorly understood. To gain insights into mechanism detergent destabilization GPCRs, we used atomistic dynamics simulations thermostabilized adenosine receptor (A
Protein tyrosine phosphatase non-receptor type 5 (PTPN5, STEP) is a brain specific that regulates synaptic function and plasticity by modulation of N-methyl-d-aspartate receptor (NMDAR) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR) trafficking. Dysregulation STEP has been linked to neurodegenerative neuropsychiatric diseases, highlighting this enzyme as an attractive therapeutic target for drug discovery. Selective targeting with small molecules hampered high conservation the...