A5025443242- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Bacterial biofilms and quorum sensing
- Cancer Genomics and Diagnostics
- Antibiotics Pharmacokinetics and Efficacy
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Retinal Development and Disorders
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Pneumonia and Respiratory Infections
- Connective Tissue Growth Factor Research
- Lung Cancer Diagnosis and Treatment
- Connexins and lens biology
- Lipid Membrane Structure and Behavior
- Crystallization and Solubility Studies
- Retinal Diseases and Treatments
- Single-cell and spatial transcriptomics
- Gastric Cancer Management and Outcomes
- Analytical Methods in Pharmaceuticals
- Advanced Biosensing Techniques and Applications
James S. McDonnell Foundation
2018-2023
Washington University in St. Louis
2018-2023
Center for Drug Evaluation and Research
2020-2021
United States Food and Drug Administration
2020-2021
Centre for Drug Research and Development
2021
Nankai University
2005-2020
University of Florida
2011-2018
Johns Hopkins University
2014-2018
Johns Hopkins Medicine
2015-2018
Institute for Stem Cell Biology and Regenerative Medicine
2011
Retinal and choroidal neovascularization (NV) vascular leakage contribute to visual impairment in several common ocular diseases. The angiopoietin/TIE2 (ANG/TIE2) pathway maintains integrity, negative regulators of this are potential therapeutic targets for these Here, we demonstrated that endothelial-protein tyrosine phosphatase (VE-PTP), which negatively regulates TIE2 activation, is upregulated hypoxic endothelial cells, particularly retinal NV. Intraocular injection an anti-VE-PTP...
Identification of neoantigens is a critical step in predicting response to checkpoint blockade therapy and design personalized cancer vaccines. This cross-disciplinary challenge, involving genomics, proteomics, immunology, computational approaches. We have built framework called pVACtools that, when paired with well-established genomics pipeline, produces an end-to-end solution for neoantigen characterization. supports identification altered peptides from different mechanisms, including...
Abstract Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, open-source software package designed to integrate somatic variants from genomic data with splice junctions bulk or single cell transcriptomic identify cause aberrant splicing. We apply over 9000 tumor samples both DNA RNA sequence data. discovers...
Abstract Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, open-source software package designed to integrate somatic variants from genomic data with splice junctions bulk or single cell transcriptomic identify cause aberrant splicing. was applied over 9,000 tumor samples both DNA RNA sequence data. We...
On April 17, 2020, the FDA approved tucatinib in combination with trastuzumab and capecitabine for treatment of patients advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases, who have received one more prior anti-HER2-based regimens setting. This was first new molecular entity evaluated under Project Orbis, an Oncology Center Excellence initiative, which supports concurrent review oncology drugs by multiple global health authorities. Approval based on...
On December 18, 2020, the FDA approved osimertinib as adjuvant therapy in patients with non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or 21 (L858R) mutations, detected by an FDA-approved test. The approval was based on ADAURA study, which 682 NSCLC were randomized to receive (n = 339) placebo 343). Disease-free survival (DFS) overall population (stage IB-IIIA) improved for who received osimertinib, HR of 0.20; 95% confidence interval (CI), 0.15-0.27; P < 0.0001....
Neoantigens are tumor-specific peptide sequences resulting from sources such as somatic DNA mutations. Upon loading onto major histocompatibility complex (MHC) molecules, they can trigger recognition by T cells. Accurate neoantigen identification is thus critical for both designing cancer vaccines and predicting response to immunotherapies. Neoantigen prioritization relies on correctly whether the presenting sequence successfully induce an immune response. Because most mutations...
Objectives: BMS-986288 is a next generation anti-CTLA-4 monoclonal antibody that integrates the Probody® [1] and non-fucosylation technologies [2] for selective tumor targeting increased dependent cellular cytotoxicity, respectively. being evaluated alone in combination with nivolumab advanced solid tumors Phase 1/2 study (Study CA043001, NCT03994601). Safety, PK, preliminary efficacy were explored monotherapy at doses of 20, 40, 80, 160, 320, 480 mg Q4W part 1A (mono escalation); 120 160...
Blood vessels are formed during development and tissue repair through a plethora of modifiers that coordinate efficient vessel assembly in various cellular settings. Here we used the yeast 2-hybrid approach demonstrated broad affinity connective growth factor (CCN2/CTGF) to C-terminal cystine knot motifs present key angiogenic regulators Slit3, von Willebrand factor, platelet-derived factor-B, VEGF-A. Biochemical characterization histological analysis showed close association CCN2/CTGF with...
Abstract A sensitive electrochemical immunosensor was developed for detecting fumonisin B 1 (FB ) in corn using the single‐walled carbon nanotubes/chitosan. The detection mechanism of based on an indirect competitive binding to a fixed amount anti‐FB between free FB and ‐bovine serum albumin, which conjugated covalently functionalized nanotubes/chitosan laid glass electrode. anti‐rabbit immunoglobulin G secondary antibody labeled with alkaline phosphatase then bound electrode surface through...
The aim of this study was to examine the relationships between N-acetyltransferase genotypes, pharmacokinetics, and tolerability granular slow-release para-aminosalicylic acid (GSR-PAS) in tuberculosis patients. a randomized, two-period, open-label, crossover design wherein each patient received 4 g GSR-PAS twice daily or 8 once alternately. PAS concentration-time profiles were modeled by one-compartment disposition model with three transit compartments series describe its absorption....
The combination of aztreonam-avibactam is active against multidrug-resistant Enterobacteriaceae that express metallo-β-lactamases. A complex synergistic interaction exists between aztreonam and avibactam bactericidal activities have not been quantitatively explored. two-state semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) logistic growth model was developed to account for antimicrobial in the bacteria-mediated degradation inhibition by avibactam. predicted changing regimens 2 g plus...
Purpose.: To investigate the function of connective tissue growth factor (CTGF), a matricellular protein CCN (Cyr61/CTGF/Nov) family, in retinal vasculature during development and ischemia. Methods.: CTGF expression was determined using RT-PCR, immunohistochemistry, transgenic mice carrying promoter-driven-GFP. antibody intraocularly injected into neonates at postnatal day (P)2, its effect on angiogenesis analyzed P4. Transgenic animals expressing GFP regulated by glial fibrillary acidic...
To characterize quantitatively the effect of avibactam in potentiating ceftazidime against MDR Pseudomonas aeruginosa by developing a mathematical model to describe bacterial response constant concentration time–kill information and validating it using both time-varying concentration–effect data from vitro vivo infection systems. The time course population dynamics presence static concentrations was modelled two-state pharmacokinetic/pharmacodynamic (PK/PD) model, consisting active resting...
A pyocyanin overproducer with insertional inactivation of ptsP gene was isolated from a mini-Mu insertion library in Pseudomonas aeruginosa PA68. The mutation complemented by functional trans. pyocyanin-overproducing phenotype also found mutant constructed replacement the P. PAO1 strain. Reporter plasmids P(qscR)-lacZ, P(lasI)-lacZ and P(rhlI)-lacZ were beta-galactosidase activity mutant/wild-type background measured. results showed that lack Enzyme I(Ntr) (EI(Ntr), encoded ptsP) decreased...
Flagella-mediated motility is recognized as one of the major factors contributing to virulence in Pseudomonas aeruginosa. During a screening mini-Mu transposon mutant library P. aeruginosa PA68, partially deficient swimming and swarming was identified new locus that encodes predicted protein unknown function annotated PA5017 PAO1 genome sequence. Chemotaxis plate assay indicated inactivation gene led decreased chemotactic response. Complementation with wild-type restored normal chemotaxis...