A5037903003- Genomics and Chromatin Dynamics
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Particle physics theoretical and experimental studies
- RNA and protein synthesis mechanisms
- TGF-β signaling in diseases
- Neutrino Physics Research
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Bioinformatics and Genomic Networks
- Astrophysics and Cosmic Phenomena
- CRISPR and Genetic Engineering
- PI3K/AKT/mTOR signaling in cancer
- Radiation Detection and Scintillator Technologies
- Scientific Research and Discoveries
- Connective Tissue Growth Factor Research
- Gene Regulatory Network Analysis
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Biopolymer Synthesis and Applications
- Colorectal Cancer Treatments and Studies
- Ubiquitin and proteasome pathways
- Muon and positron interactions and applications
- Chromosomal and Genetic Variations
Biogen (United States)
2017-2024
Ono Pharmaceutical (United States)
2018-2022
Merck (Germany)
2020-2021
Research & Development Institute
2018-2021
Rutgers, The State University of New Jersey
2010-2015
Quantitative BioSciences
2010-2013
Blockade of PD-L1 and TGF-β pathways with M7824 activates effective innate adaptive antitumor immune responses.
The MINERvA experiment is designed to perform precision studies of neutrino-nucleus scattering using $\nu_\mu$ and ${\bar\nu}_\mu$ neutrinos incident at 1-20 GeV in the NuMI beam Fermilab. This article presents a detailed description \minerva detector describes {\em ex situ} techniques employed characterize monitor its performance. comprised finely-segmented scintillator-based inner tracking region surrounded by electromagnetic hadronic sampling calorimetry. upstream portion includes planes...
Localized radiotherapy (RT) induces an immunogenic antitumor response that is in part counterbalanced by activation of immune evasive and tissue remodeling processes, e.g., via upregulation programmed cell death-ligand 1 (PD-L1) transforming growth factor β (TGF-β). We report a bifunctional fusion protein simultaneously inhibits TGF-β PD-L1, bintrafusp alfa (BA), effectively synergizes with radiotherapy, leading to superior survival multiple therapy-resistant murine tumor models poor...
We report a study of muon neutrino charged-current quasi-elastic events in the segmented scintillator inner tracker MINERvA experiment running NuMI beam at Fermilab. The were selected by requiring {\mu}^- and low calorimetric recoil energy separated from interaction vertex. measure flux-averaged differential cross-section, d{\sigma}/dQ^2, particle content final state. Deviations are found between measured d{\sigma}/dQ^2 expectations model independent nucleons relativistic Fermi gas. also...
We have isolated muon anti-neutrino charged-current quasi-elastic interactions occurring in the segmented scintillator tracking region of MINERvA detector running NuMI neutrino beam at Fermilab. measure flux-averaged differential cross-section, d{\sigma}/dQ^2, and compare to several theoretical models scattering. Good agreement is obtained with a model where nucleon axial mass, M_A, set 0.99 GeV/c^2 but vector form factors are modified account for observed enhancement, relative free case,...
We use genome-wide nucleosome maps to study sequence specificity of intrinsic histone-DNA interactions. In contrast with previous approaches, we employ an analogy between a classical one-dimensional fluid finite-size particles in arbitrary external potential and arrays DNA-bound histone octamers. derive analytical solution infer free energies formation directly from occupancies measured high-throughput experiments. The sequence-specific part is then captured by fitting them sum assigned...
Bintrafusp alfa (BA) is a bifunctional fusion protein designed for colocalized, simultaneous inhibition of two immunosuppressive pathways, transforming growth factor-β (TGF-β) and programmed death-ligand 1 (PD-L1), within the tumor microenvironment (TME). We hypothesized that targeting PD-L1 to by BA colocalizes TGF-β trap (TGF-βRII) TME, enabling it sequester in more effectively than systemic blockade, thereby enhancing antitumor activity.Multiple technologies were used characterize binding...
Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis is upregulated fibroblasts myofibroblasts disease. Here, we investigated the role of CTGF fibrogenic cells. In mice, tissue-specific inducible overexpression by kidney pericytes had no bearing on nephrogenesis or homeostasis but exacerbated inflammation fibrosis after ureteral obstruction. These effects...
One-dimensional arrays of nucleosomes (DNA-bound histone octamers separated by stretches linker DNA) fold into higher-order chromatin structures which ultimately make up eukaryotic chromosomes. Chromatin structure formation leads to 10-11 base pair (bp) discretization lengths caused the smaller free energy cost packaging a regular fiber if their rotational setting (defined DNA helical twist) is conserved. We describe nucleosome positions along using thermodynamic model finite-size particles...
Eukaryotic chromatin architecture is affected by intrinsic histone-DNA sequence preferences, steric exclusion between nucleosome particles, formation of higher-order structures, and in vivo activity remodeling enzymes.To disentangle sequence-dependent positioning from the other factors, we have created two high-throughput maps nucleosomes assembled vitro on genomic DNA nematode worm Caenorhabditis elegans. A comparison positions with those observed a mixed-stage, mixed-tissue population C....
Abstract Sequence-specific interactions between proteins and DNA play a central role in replication, repair, recombination, control of gene expression. These can be studied vitro using microfluidics, protein-binding microarrays (PBMs), other high-throughput techniques. Here we develop biophysical approach to predicting protein–DNA binding specificities from data. Our algorithm, called BindSter, model alternative DNA-binding modes multiple protein species competing for access DNA, while...
Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain TGF-βRII (a TGF-β "trap") fused to human IgG1 mAb blocking PD-L1, is being evaluated for efficacy and safety in solid tumor indications as monotherapy combination with small-molecule drugs. We perpetrator drug-drug interaction (DDI) potential bintrafusp alfa via cytochrome P4503A4 (CYP3A4) enzyme modulation, which responsible metabolism majority The holistic approach included (1) evaluation...
Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of cancer. Identification biomarkers that are predictive response to investigational therapies will help identify patients more likely clinically benefit from treatment. Bintrafusp alfa (M7824) innovative first-in-class bifunctional fusion protein composed the extracellular domain TGF-βRII receptor (a TGF-β “trap”) fused a human IgG1 mAb blocking PD-L1. In this expansion cohort global, phase 1, open-label...
Abstract Sequence-specific interactions between proteins and DNA play a central role in replication, repair, recombination, control of gene expression. These can be studied vitro using microfluidics, protein-binding microarrays (PBMs), other high-throughput techniques. Here we develop biophysical approach to predicting protein-DNA binding specificities from data. Our algorithm, called BindSter, accommodates multiple protein species competing for access alternative modes the same protein,...
We describe a next-generation Drosophila Protein Interaction Map – “DPIM2” established from affinity purification-mass spectrometry of 5,805 baits covering the largest fraction yet proteome. The final network contains 32,668 interactions among 3,644 proteins, organized into 632 clusters representing putative functional modules. Our analysis significantly expands pool known protein in , provides wealth annotation for poorly studied genes and, importantly, postulates previously undescribed...
Abstract Background: Bintrafusp alfa (M7824) is a first-in-class bifunctional fusion protein composed of the extracellular domain TGF-βRII receptor, to function as TGF-β “trap”, fused human IgG1 antibody blocking PD-L1, which has shown early evidence clinical activity in phase 1 studies patients with advanced solid tumors. We recently reported high expression HMGA2 triple negative breast cancer (TNBC) who experienced disease control (response or stable disease) bintrafusp treatment compared...
Abstract Background: Bintrafusp alfa (M7824) is a first-in-class bifunctional fusion protein composed of the extracellular domain TGF-βRII receptor (a TGF-β “trap”) fused to human IgG1 mAb blocking PD-L1. In expansion cohorts global, phase 1, open-label trials (NCT02517398 and NCT02699515), extensive analysis was conducted identify potential tumor biomarkers correlated with bintrafusp efficacy. Methods: Immunohistochemistry performed on archival or fresh formalin-fixed paraffin-embedded...