A5041659397- Ion Channels and Receptors
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Blood Coagulation and Thrombosis Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immunotherapy and Immune Responses
- Magnesium in Health and Disease
- Vanadium and Halogenation Chemistry
- Renin-Angiotensin System Studies
- Complement system in diseases
- Phytochemicals and Antioxidant Activities
- Cancer Immunotherapy and Biomarkers
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- HER2/EGFR in Cancer Research
- Protein Kinase Regulation and GTPase Signaling
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Hydrogen's biological and therapeutic effects
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Advanced Glycation End Products research
- Cardiac electrophysiology and arrhythmias
- Barrier Structure and Function Studies
- Bioactive Compounds and Antitumor Agents
- Sphingolipid Metabolism and Signaling
- Antimicrobial Peptides and Activities
AbbVie (United States)
2021-2023
University of Illinois Chicago
2003-2017
Illinois College
2000-2017
University of Illinois Urbana-Champaign
1996-2017
University of Chicago Medical Center
1996
Oxidative stress through the production of oxygen metabolites such as hydrogen peroxide (H2O2) increases vascular endothelial permeability. H2O2 stimulates ADP-ribose formation, which in turn opens transient receptor potential melastatin (TRPM)2 channels. Here, cells, we demonstrate transcript and protein expression TRPM2, a Ca2+-permeable, nonselective cation channel. We further show importance TRPM2 signaling increased permeability by oxidative stress. Exposure cell monolayers to sublytic...
Summary The transient receptor potential (melastatin) 2 (TRPM2), is an oxidant-activated non-selective cation channel that widely expressed in mammalian tissues including the vascular endothelium. Oxidative stress, through generation of oxygen meta-bolites H2O2, stimulates intracellular ADP-ribose formation which, turn, opens TRPM2 channels. These channels act as endogenous redox sensor for mediating oxidative stress/ROS-induced Ca2+ entry and subsequent specific Ca2+-dependent cellular...
TRPM2 (transient receptor potential melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca2+ entry response to intracellular generation of adenosine diphosphoribose-the ligand.Because polymorphonuclear neutrophils (PMN) interaction with ECs generates reactive oxygen species, we addressed the possible role mechanism transendothelial migration PMNs.We observed defective PMN transmigration lipopolysaccharide challenge adult mice which EC conditionally deleted...
Bradykinin (BK) and kallidin (Lys-BK), liberated from kininogens by kallikreins, are ligands of the BK B<sub>2</sub> receptor. We investigated whether besides releasing peptide agonist, could also activate receptor directly. studied effect porcine human recombinant tissue kallikrein plasma on [Ca<sup>2+</sup>]<sub>i</sub> mobilization [<sup>3</sup>H]arachidonic acid release cultured cells stably transfected to express (CHO/B<sub>2</sub>, MDCK/B<sub>2</sub>, HEK/B<sub>2</sub>), endothelial...
Rationale: Oxidants generated by activated endothelial cells are known to induce apoptosis, a pathogenic feature of vascular injury and inflammation from multiple pathogeneses. The melastatin-family transient receptor potential 2 (TRPM2) channel is an oxidant-sensitive Ca 2+ permeable implicated in mediating apoptosis; however, the mechanisms gating supranormal influx required for initiating apoptosis not understood. Objective: Here, we addressed role TRPM2 its interaction with short splice...
Transient receptor potential melastatin-2 (TRPM2) channel is a nonselective cation that mediates influx of Ca(2+) and Na(+) with relative permeability PCa:PNa ≈0.6 in response to cellular oxidative stress. As angiogenesis ischemic neovascularization are both significantly dependent on oxidant signaling, here we investigated the possible role vascular endothelial growth factor (VEGF)-induced reactive oxygen species production activating TRPM2-dependent signaling mechanism...
Kallikreins cleave plasma kininogens to release the bioactive peptides bradykinin (BK) or kallidin (Lys-BK). These then activate widely disseminated B2 receptors with consequences that may be either noxious beneficial. We used cultured cells show kallikrein can bypass kinin BK directly. To exclude intermediate kininogen uptake from medium, we and maintained in medium entirely free of animal proteins. compared responses stably transfected Chinese hamster ovary (CHO) express human (CHO B2)...
Prolactin receptor (PRLR) is an attractive antibody therapeutic target with expression across a broad population of breast cancers. Antibody efficacy, however, may be limited to subtypes either PRLR overexpression and/or those where estradiol no longer functions as mitogen and are, therefore, reliant on signaling for growth. In contrast potent antibody-drug conjugate (ADC) provide improved outcomes extending beyond overexpressing or estradiol-insensitive cancer populations.We derived novel...
Bradykinin (BK) or kallikreins activate B2 receptors (R) that couple Galpha(i) and Galpha(q) proteins to release arachidonic acid (AA) elevate intracellular Ca2+ concentration ([Ca2+]i). Thrombin cleaves the protease-activated-receptor-1 (PAR1) couples Galpha(i), Galpha(q), Galpha(12/13) proteins. In Chinese hamster ovary cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA by B2R agonists. We explored mechanisms of cooperativity between...
CD3 bispecific T-cell engagers (TCE), comprised of a tumor-targeting domain linked to binding domain, function by bridging target-positive tumors and CD3-expressing effector T cells enabling redirected cell-mediated killing tumor cells. Although the majority molecules in clinical development incorporate antibody-based domains, many tumor-associated antigens derive from intracellular proteins are not accessible targeting via antibody. Intracellular processed into short peptide fragments...
The prototypical extracellular phospholipid mediator, lysophosphatidic acid (LPA), exhibits growth factor-like properties and represents an important survival factor in serum. This potent mesangial cell mitogen is increased conditions associated with glomerular injury. It also a known activator of the classic mitogen-activated protein kinase (MAPK) pathway, which plays role regulation hexokinase (HK) activity. To better understand mechanisms coupling metabolism to injury, we examined ability...
<div>Abstract<p>CD3 bispecific T cell engagers (TCE), comprised of a tumor targeting domain linked to CD3 binding domain, function by bridging target-positive tumors and CD3-expressing effector cells enabling redirected cell-mediated killing cells. Although the majority molecules in clinical development incorporate tumor-targeting antibody-based domains, many tumor-associated antigens derive from intracellular proteins are not accessible via antibody. Intracellular processed into...
<p>A prostate tumor cell line (PC3M-A2/beta 2M) was inoculated subcutaneously in the right flank of CD34-humanized NSG mice. Mice were treated intravenously at indicated time points with either vehicle or an ABBV-184 precursor molecule, and size monitored. Tumors experienced transient regression growth inhibition prior to harvest for analysis tumor-infiltrating immune cells.</p>
<p>A prostate tumor cell line (PC3M-A2/beta 2M) was inoculated subcutaneously in the right flank of CD34-humanized NSG mice. Mice were treated intravenously at indicated time points with either vehicle or an ABBV-184 precursor molecule, and size monitored. Tumors experienced transient regression growth inhibition prior to harvest for analysis tumor-infiltrating immune cells.</p>
<div>Abstract<p>CD3 bispecific T cell engagers (TCE), comprised of a tumor targeting domain linked to CD3 binding domain, function by bridging target-positive tumors and CD3-expressing effector cells enabling redirected cell-mediated killing cells. Although the majority molecules in clinical development incorporate tumor-targeting antibody-based domains, many tumor-associated antigens derive from intracellular proteins are not accessible via antibody. Intracellular processed into...
<p>A prostate tumor cell line (PC3M-A2/beta 2M) was inoculated subcutaneously in the right flank of CD34-humanized NSG mice. Mice were treated intravenously at indicated time points with either vehicle or an ABBV-184 precursor molecule, and size monitored. Tumors experienced transient regression growth inhibition prior to harvest for analysis tumor-infiltrating immune cells.</p>