A5071178798- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Mast cells and histamine
- Click Chemistry and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Chemical Synthesis and Analysis
- Synthesis and Biological Evaluation
- HIV Research and Treatment
- Receptor Mechanisms and Signaling
- Health Systems, Economic Evaluations, Quality of Life
- Phenothiazines and Benzothiazines Synthesis and Activities
- Reconstructive Surgery and Microvascular Techniques
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- Olfactory and Sensory Function Studies
- Plant Virus Research Studies
- Disaster Response and Management
- Statistical Methods in Clinical Trials
- Synthesis and biological activity
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Signaling Pathways in Disease
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Insect Resistance and Genetics
Northwestern University
2022-2024
City of Hope
2017-2023
Vanderbilt Health
2022
Austrian Institute for Health Technology Assessment GmbH
2021
Beckman Research Institute
2019
City Of Hope National Medical Center
2016-2019
NSK (United States)
2014-2018
Goethe University Frankfurt
2010-2016
Carmel Medical Center
2015-2016
Goethe Institute
2013
We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design Genuine Structures) features ligand-based strategy automated ‘in silico’ assembly potentially novel bioactive compounds. quality designed compounds is assessed by graph kernel measuring their similarity to known reference ligands in terms structural and pharmacophoric features. implemented deterministic compound construction procedure that explicitly considers...
Purpose: Multiple myeloma remains an incurable malignancy of plasma cells despite considerable advances in treatment. The purpose the study was to develop novel chimeric antigen receptors (CAR) for treatment multiple and explore combinatorial therapy using CAR T immunomodulatory drugs such as lenalidomide increasing efficacy.Experimental Design: We redirected central memory express second-generation CAR-specific CS1 adoptively transferred them into tumor-bearing mice test their anti-multiple...
Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive cell therapy. Generating potent CAR is increasing importance in the field. Studies demonstrated Akt pathway regulation differentiation memory formation. We now investigate whether inhibition signaling during ex vivo expansion can promote generation with enhanced antitumor activity following therapy a murine leukemia xenograft model.Various subsets...
BAFF receptor is a target for CAR T cell therapy of B malignancies, circumventing issues with CD19 antigen loss in tumors.
Abstract: Previous studies have suggested a potential link between histamine H 3 receptors (H R) signaling and anxiolytic-like antidepressant-like effects. The aim of this study was to investigate the acute effects ST-1283, novel R antagonist, on anxiety-related depression-related behaviors in comparison with those diazepam fluoxetine. ST-1283 were evaluated using elevated plus maze test, open field marbles burying tail suspension novelty suppressed feeding forced swim test male C57BL/6...
The polymerase-associated factor 1 complex (PAF1C) is a key, post-initiation transcriptional regulator of both promoter-proximal pausing and productive elongation catalyzed by RNA Pol II also involved in repression viral gene expression during human immunodeficiency virus-1 (HIV-1) latency. Using molecular docking-based compound screen silico global sequencing-based candidate evaluation vivo, we identified first-in-class, small-molecule inhibitor PAF1C (iPAF1C) that disrupts PAF1 chromatin...
Abstract Lymphomas with central nervous system (CNS) involvement confer a worse prognosis than those without CNS involvement, and patients currently have limited treatment options. T cells genetically engineered CD19-targeted chimeric antigen receptors (CAR) are effective against B-cell malignancies show tremendous potential in the of systemic lymphoma. We aimed to leverage this strategy toward more therapy for lymphoma disease. NOD-scid IL2Rgammanull (NSG) mice and/or were treated CD19-CAR...
Histamine plays an important role as neurotransmitter and chemical mediator in multiple physiological pathophysiological processes central peripheral tissues. In the last century extensive study of its actions human body, resulted identification four G protein-coupled receptor (GPCR) subtypes (H1R-H4R), mediating numerous effects. The successful application H1R H2R antagonists/inverse agonists treatment allergic conditions gastric ulcer proved that these two receptors are excellent drug...
Adoptive transfer of CD19-specific chimeric antigen receptor (CD19CAR) T cells can induce dramatic disease regression in patients with B cell malignancies. CD19CAR therapy may be limited by insufficient engraftment and persistence, resulting tumor relapse. We previously demonstrated a proof principle that cytomegalovirus (CMV)-specific isolated enriched prior to transduction produce CMV-CD19CAR cells, these expanded vivo through CMV vaccination, better control murine model. Here we developed...
The tetravalent dengue vaccine candidate, TAK-003, induces a functional antibody response, but the titers of antibodies against four serotypes virus (DENV) can vary. Here, through transcriptomic analysis on whole blood collected from recipients two-dose schedule we examine gene expression, splicing, and transcript isoform-level changes for both protein-coding noncoding genes to broaden our understanding immune response. Our reveals dynamic pattern vaccine-associated regulation long RNAs...
Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) mediates tumor cell–macrophage interactions, and has been shown to induce both metalloproteinases (MMPs) vascular endothelial growth factor (VEGF). However, the epitope responsible for MMP induction is controversial, VEGF yet unknown. We generated a novel anti-EMMPRIN antibody directed against specific that successfully inhibited production of MMP-9 in vitro co-culture systems, exhibiting U-shaped dose response. Furthermore, this...
Abstract: Phenytoin (PHT), valproic acid, and modern antiepileptic drugs (AEDs), eg, remacemide, loreclezole, safinamide, are only effective within a maximum of 70%–80% epileptic patients, in many cases the clinical use AEDs is restricted by their side effects. Therefore, continuous need remains to discover innovative chemical entities for development active safer AEDs. Ligands targeting central histamine H 3 receptors (H Rs) epilepsy might be promising therapeutic approach. To determine...
The persistence of HIV-1 in long-lived latent reservoirs during suppressive antiretroviral therapy (ART) remains one the principal barriers to a functional cure. Blocks transcriptional elongation play central role maintaining state, and several latency reversal strategies focus on release positive transcription factor b (P-TEFb) from sequestration by negative regulatory complexes, such as 7SK complex BRD4. Another major cellular reservoir P-TEFb is Super Elongation Complexes (SECs), which...
A free-flap graft refers to the free transfer of tissue cover defects caused by trauma or malperfusion in plastic surgery. The basic principle, which makes a flap working is an adequate blood flow. We applied new techniques are able detect flow anastomosis and dermal subdermal layers reliable way.To this end we innovative Ultrasound-techniques (contrast enhanced high resolution Ultrasound (US), color coded Doppler sonography (CCDS), Cross Beamtrade mark, Power Doppler, Tissue Harmonic...
Evaluation of post-surgery tissue perfusion free flaps the lower leg with contrast enhanced harmonic imaging (CHI), laser-induced indocyanine green (ICG) fluorescence angiography and magnetic resonance (MRI).10 patients limb were evaluated CHI, ICG-fluorescence weighted MRI. Perfusion MRI was performed after intravenous bolus injection 25 ml Gd-DTPA. The ICG detected by a near-infrared-laser device (lambda em = 780 nm). Ultrasound carried out an experienced examiner linear probe 2.4 SonoVue....
Previously, we have identified a new epitope in EMMPRIN, multifunctional protein that mediates tumor cell–macrophage interactions and induces both MMP-9 VEGF. Here, synthesized this as an octa-branched multiple antigenic peptide (MAP) to vaccinate mice implanted with subcutaneous syngeneic colon (CT26), prostate (TRAMP-C2) or renal (RENCA) cell line carcinomas. Vaccination inhibited, sometimes regressed, growth dose-dependent manner, reaching 94%, 71% 72% inhibition, respectively, at 50 μg...
Iron-containing ligands targeting the human histamine H3 receptor (hH3R) were prepared. The compounds contain ferrocene sandwich complexes coupled via different linkers to a basic hH3R antagonist/inverse agonist pharmacophore. In click chemistry approach, triazole was successfully inserted as new linking element. Two ferrocenylmethylamines and ferrocenyltriazole most affine within this series, showing binding in nano- subnanomolar concentration range.
According to the AMNOG act, German Federal Joint Committee (G-BA) determines additional benefit of new medicines as a basis for subsequent price negotiations. Pharmaceutical companies may withdraw their medications from market at any time during process. This analysis aims compare recommendations in clinical guidelines and HTA appraisals that were withdrawn since introduction 2011. Medications between January 2011 June 2016 following assessment categorized opt-outs (max. 2 weeks after start...
Purpose: The aim of the prospective study was to evaluate macro- and microcirculation in center periphery free flaps with high resolution vascular ultrasound. Material: Fifteen patients parascapular after lower limb tra