A5054918044- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Multiple Myeloma Research and Treatments
- Cystic Fibrosis Research Advances
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Hedgehog Signaling Pathway Studies
- Cancer therapeutics and mechanisms
- Microtubule and mitosis dynamics
- Viral Infectious Diseases and Gene Expression in Insects
- Epigenetics and DNA Methylation
- Statistical Methods in Clinical Trials
- Advanced Biosensing Techniques and Applications
- Neonatal Respiratory Health Research
- Blood disorders and treatments
- International Labor and Employment Law
- Biochemical and Molecular Research
- Teacher Education and Leadership Studies
- Asthma and respiratory diseases
- Posttraumatic Stress Disorder Research
- Monoclonal and Polyclonal Antibodies Research
University of Redlands
2022
University of California, Santa Barbara
2022
Boston College
2022
Copper Mountain College
2022
St. Jude Children's Research Hospital
2020-2021
Max Planck Institute of Molecular Physiology
2010-2018
TU Dortmund University
2012-2017
Max Planck Institute for Infection Biology
2017
Charité - Universitätsmedizin Berlin
2017
Albert Einstein College of Medicine
1982-2007
Aberrant hedgehog (Hh) signaling contributes to the pathogenesis of multiple cancers. Available inhibitors target Smoothened (Smo), which can acquire mutations causing drug resistance. Thus, compounds that inhibit Hh downstream Smo are urgently needed. We identified dynarrestin, a novel inhibitor cytoplasmic dyneins 1 and 2. Dynarrestin acts reversibly dynein 1-dependent microtubule binding motility in vitro without affecting ATP hydrolysis. It rapidly inhibits endosome movement living cells...
Rationale: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment intravenous antimicrobials is common; however, there scant evidence to support a standard treatment duration. Objectives: To test differing durations for CF Methods: STOP2 (Standardized Pulmonary Exacerbations 2) was multicenter, randomized, controlled clinical trial in exacerbations among adults CF. After 7-10 days treatment,...
Inhibition of members the bromodomain and extraterminal (BET) family proteins has proven a valid strategy for cancer chemotherapy. All BET identified to date contain two bromodomains (BD; BD1 BD2) that are necessary recognition acetylated lysine residues in N-terminal regions histones. Chemical matter targets (BETi) also interact via these domains. Molecular cellular data indicate BD2 have different biological roles depending upon their context, with particularly associated cancer. We...
B cell-specific expression of immunoglobulin heavy chain (IgH) genes utilizes two cis regulatory regions, the intronic enhancer (Emicro), located in J(H)-Cmicro intron, and a complex region that lies 3' to IgH gene cluster, RR. We hypothesized RR is involved transcription plasma cells via physical interaction between distal enhancers target V(H) sequences, with loop formation by intervening DNA. In support this hypothesis we report sequence data at DNA recombination breakpoints as evidence...
In the third place: Inspired by tetrahydroisoquinoline (THIQ) alkaloid noscapine, inhibitors of tubulin polymerization that bind to a site different from colchicine and vinca binding sites have been synthesized. One compound is more potent than noscapine in HeLa cells can overcome resistance chemotherapeutics.
Abstract Ras proteins are of importance in cell proliferation, and hence their mutated forms play causative roles many kinds cancer different tissues. Inhibition the Ras‐depalmitoylating enzyme acyl protein thioesterases APT1 ‐2 is a new approach to modulating cycle. Here we present boronic borinic acid derivatives as class potent nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays turned out inhibit human competitive mode. Furthermore,...
Abstract Neutrophils are short‐lived leukocytes that migrate to sites of infection as part the acute immune response, where they phagocytose, degranulate, and form neutrophil extracellular traps (NETs). During NET formation, nuclear lobules neutrophils disappear chromatin expands and, accessorized with neutrophilic granule proteins, is expelled. NETs can be pathogenic in, for example, sepsis, cancer, autoimmune cardiovascular diseases. Therefore, identification inhibitors formation great...
Abstract Introduction: Aberrant hedgehog (Hh) pathway activation contributes to the pathogenesis of multiple cancers. Currently available Hh inhibitors target Smoothened (Smo) which can acquire mutations causing drug resistance. Therefore, a major challenge is identify compounds that inhibit signaling downstream Smoothened. Methods: We conducted high-throughput screening (HTS) campaign 337,000 small molecules using Hh-dependent differentiation assay C3H10T1/2 cells into osteoclasts. Primary...
Abstract Pediatric sarcomas represent a heterogeneous group of malignancies that exhibit variable response to DNA damaging chemotherapy. Schlafen family member 11 protein (SLFN11) increases sensitivity replicative stress, and SLFN11 gene silencing has been implicated as common mechanism drug resistance in tumors adults. We found be widely expressed our cohort pediatric sarcomas. In sarcoma cell lines, expression strongly correlated with the PARP inhibitor talazoparib (TAL) topoisomerase I...
<p>This file contains 16 Supplemental tables and 14 Figures, as well numerous NMR traces, synthetic chemistry schemes, mass spectra, tables, multiple graphics related to gene expression profiles, dose response curves, x-ray structures, westerns, etc.</p>
<div>Abstract<p>Inhibition of members the bromodomain and extraterminal (BET) family proteins has proven a valid strategy for cancer chemotherapy. All BET identified to date contain two bromodomains (BD; BD1 BD2) that are necessary recognition acetylated lysine residues in N-terminal regions histones. Chemical matter targets (BETi) also interact via these domains. Molecular cellular data indicate BD2 have different biological roles depending upon their context, with particularly...
<p>This file contains 16 Supplemental tables and 14 Figures, as well numerous NMR traces, synthetic chemistry schemes, mass spectra, tables, multiple graphics related to gene expression profiles, dose response curves, x-ray structures, westerns, etc.</p>
<div>Abstract<p>Inhibition of members the bromodomain and extraterminal (BET) family proteins has proven a valid strategy for cancer chemotherapy. All BET identified to date contain two bromodomains (BD; BD1 BD2) that are necessary recognition acetylated lysine residues in N-terminal regions histones. Chemical matter targets (BETi) also interact via these domains. Molecular cellular data indicate BD2 have different biological roles depending upon their context, with particularly...
This data set contains the used in Twarog et al. (2021) to examine robustness and utility of response surface models drug combination analysis. It includes simulated experimental for evaluation traditional index methods, as well a processed library interaction metrics evaluated on Merck OncoPolyPharmacology Screen (O'Neil al., 2016), scripts implement those all tested combinations that screen, evaluate performance comparison with real-world mechanistic classifications. Finally, from several...