A5035126321- DNA and Nucleic Acid Chemistry
- DNA Repair Mechanisms
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Phagocytosis and Immune Regulation
- Receptor Mechanisms and Signaling
- Childhood Cancer Survivors' Quality of Life
- Brain Metastases and Treatment
- Multiple Myeloma Research and Treatments
- Fungal and yeast genetics research
- Cancer Treatment and Pharmacology
- Bacterial Genetics and Biotechnology
- Acute Lymphoblastic Leukemia research
- Immunotherapy and Immune Responses
- Global Public Health Policies and Epidemiology
- Nuclear Structure and Function
- MicroRNA in disease regulation
- Lung Cancer Research Studies
- Adolescent and Pediatric Healthcare
- RNA modifications and cancer
- Fungal Plant Pathogen Control
- Microbial Natural Products and Biosynthesis
- T-cell and Retrovirus Studies
- Adenosine and Purinergic Signaling
- Complement system in diseases
University of California, San Diego
2017-2021
Queen's Medical Center
2021
University of Hawaii System
2021
Weatherford College
2021
University of California, Davis
2021
Bristol-Myers Squibb (United States)
2021
UC San Diego Health System
2020
Columbia University
2015-2016
University of Vermont
2010-2015
University of Michigan
2015
How a receptor transmits signal G protein–coupled receptors (GPCRs) transmit diverse external signals into the cell. When activated by an outside stimulus, they bind to protein inside cell and accelerate exchange of bound guanosine diphosphate (GDP) nucleotide for triphosphate, which initiates intercellular signaling. Dror et al. used atomic-level molecular dynamics simulations show how GPCRs enhance GDP release. The is dynamic frequently adopts conformation that exposes even without bound....
CD47 is the only 5-transmembrane (5-TM) spanning receptor of immune system. Its extracellular domain (ECD) a cell surface marker self that binds SIRPα and inhibits macrophage phagocytosis, cancer immuno-therapy approaches in clinical trials are focused on blocking CD47/SIRPα interaction. We present crystal structure full length bound to function-blocking antibody B6H12. ECD tethered TM via six-residue peptide linker (114RVVSWF119) forms an extended loop (SWF loop), with fundamental role...
Significance Structure-based drug design depends on the ability to predict both three-dimensional structures of candidate molecules bound their targets and associated binding affinities. We demonstrate that one can substantially improve accuracy these predictions using easily obtained data about completely different bind same target without requiring any target-bound molecules. The approach we developed integrate physical data-driven modeling may find a variety applications in rapidly...
Abstract Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co‐occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden mutational status), treatment patients. The medical records of 394 from two institutions (Columbia University, USA Tohoku Japan) were reviewed. Information collected included presence histologic subtype, stage, number metastases,...
Rad51 protein promotes homologous recombination in eukaryotes. Recombination activities are activated by filament assembly on ssDNA. Previous studies of yeast showed that His352 occupies an important position at the interface, where it could relay signals between subunits and active sites. To investigate, we characterized H352A H352Y mutants, solved structure H352Y. forms catalytically competent but salt-labile complexes In contrast, salt-resistant ssDNA, is defective nucleotide exchange,...
Abstract Background The mechanisms responsible for resistant disease or recurrence of non‐Hodgkin lymphoma (NHL) in children cover a wide spectrum from drug resistance to genetic mutations. A unique mechanism suggesting the role mitochondria as key energy source is studied following clinical observation where pediatric Burkitt (BL) specimens patients on therapy were found have increased copies DNA (mtDNA) which shown be positive minimal residual and/or persistent (MRD/PD). This study...
Prostate cancer is the second most common in men worldwide. While clinicians commonly see metastases to bones and lymph nodes, it may infrequently spread more uncommon locations. We report an unusual case of 83-year-old patient with previously treated prostate adenocarcinoma who presents symptomatic testis brain absence widely disseminated disease. This highlights importance including metastatic disease differential for patients a history newly discovered mass until evaluation tissue can be...
Malignant infiltration accounts for 0.5% of acute liver failure cases, with non-Hodgkin's lymphoma the predominant cause. Adult T-cell lymphoma/leukemia (ATLL) is a rarer source hepatitis, only 3 cases reported and all resulting in immediate deterioration death. ATLL rises from human T-lymphocytic virus-1 (HTLV-1), commonly found Japan (southern northern islands), Caribbean, Central South America, intertropical Africa, Romania, Iran. In Micronesia, HTLV-1 infection amongst native-born absent...
Abstract Over the past fifty years, tremendous effort has been devoted to computational methods for predicting properties of ligands that bind macromolecular targets, a problem critical rational drug design. Such generally fall into two categories: physics-based methods, which directly model ligand interactions with target given target’s three-dimensional (3D) structure, and ligand-based predict experimental measurements similar ligands. Here we present rigorous statistical framework combine...
Eukaryotic Rad51 recombinase plays a central role in maintaining genome stability by promoting homology‐directed repair of DNA double‐strand breaks and stalled replication forks. forms presynaptic filaments on single‐stranded DNA, which activates the ATPase, homologous pairing, strand exchange activities enzyme. Structure/function studies yeast reveal that coordination between ATP binding sites is mediated residues at protomer‐protomer interface loops L1 L2. Conserved Phe‐187 His‐352 play...
8530 Background: Upfront ASCT is the current standard of care for transplant-eligible NDMM. However, its use has come into question with emergence novel agents such as lenalidomide. This randomized phase III study evaluated role upfront in NDMM, Ld administered induction therapy. Methods: Patients aged 18–75 years transplant-eligible, previously untreated, NDMM were to four 28-day cycles lenalidomide (25 mg days 1–21) plus low-dose dexamethasone (40mg 1, 8, 15, 22) followed by stem-cell...
The recombinase Rad51 promotes homologous recombination in eukaryotes. Recombination is initiated when forms a presynaptic filament on ssDNA. Filament formation activates the enzymatic activities of including ssDNA-dependent ATP hydrolysis, homology search and DNA strand exchange. Proper assembly crucial for double-strand break repair avoidance cancer. Previous studies showed that yeast H352 residue, located at protomer-protomer interface near ATPase site, important allosteric communication....
Rad51 protein promotes homologous recombination in eukaryotes. Recombination activities are activated by filament assembly on single‐stranded DNA. Previous studies of yeast showed that His352 occupies an important position at the interface, where it could relay signals between subunits and active sites. Here we report 2.5A X‐ray crystallographic structure H352Y mutant Rad51. Biochemical data indicate is trapped a high‐affinity ssDNA‐binding conformation with limited catalytic turnover. The...
e20614 Background: The central nervous system (CNS) remains a common site of metastatic disease for NSCLC, especially in EGFR-driven disease. Surgery and RT are upfront treatment options but have potential early late onset complications. Osimertinib (Osi) is now approved use the front-line setting EGFR-mutated NSCLC highly CNS penetrant. A prior retrospective study showed that generation EGFR TKIs had an inferior overall survival (OS) compared to newly diagnosed brain metastases,...
TPS128 Background: Plinabulin (Plin) is a microtubule-destabilizing agent (MDA) that inhibits the polymerization of tubulin monomers and leads to disruption tumor vasculature. It has been shown in clinical studies advanced NSCLC produce significantly longer duration response when combined with docetaxel versus alone (NCT00630110). MDAs were also trigger maturation dendritic cells production pro-inflammatory cytokines, thereby enhancing T-cell proliferation. Pre-clinical have combination...
Abstract Introduction: Minority populations and individuals from socioeconomically disadvantaged backgrounds suffer high rates of cancer, yet these at-risk communities are underrepresented in the biomedical research clinical workforce. Disparities start an early age stem multiple factors, though gaps education play a role. In summer 2018, University California San Diego (UCSD) created cancer fellowship program for minority school students called Outreach Program to Inspire Underrepresented...