A5019352600- Bariatric Surgery and Outcomes
- Diet and metabolism studies
- Body Contouring and Surgery
- Streptococcal Infections and Treatments
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Neuropeptides and Animal Physiology
- Salivary Gland Disorders and Functions
- Cytokine Signaling Pathways and Interactions
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Infective Endocarditis Diagnosis and Management
- Chemical Synthesis and Analysis
- Oral microbiology and periodontitis research
- Estrogen and related hormone effects
- Gastric Cancer Management and Outcomes
- Antimicrobial Resistance in Staphylococcus
- Sphingolipid Metabolism and Signaling
- Atherosclerosis and Cardiovascular Diseases
- Cardiac pacing and defibrillation studies
- Cell death mechanisms and regulation
- Bacterial Genetics and Biotechnology
- Cholesterol and Lipid Metabolism
Gundersen Health System
2005-2022
Sanford Burnham Prebys Medical Discovery Institute
2018-2021
Discovery Institute
2018-2021
Takeda (United States)
2015-2019
Translational Research Institute for Metabolism and Diabetes
2019
Henry Ford Hospital
2017
Tufts Medical Center
2017
Northwestern University
2016
Lung Institute
2016
Duke Medical Center
2016
Transcription factors play a key role in the development and differentiation of specific lineages from multipotential progenitors. Identification these regulators determining mechanism how they activate their target genes are important for understanding normal monocytes macrophages pathogenesis common form adult acute leukemia, which monocytic cells is blocked. Our previous work has shown that monocyte-specific expression macrophage colony-stimulating factor (M-CSF) receptor regulated by...
BRCA2 mutations predispose carriers mainly to breast cancer. The vast majority of are predicted result in a truncated protein product. smallest known cancer-associated deletion removes from the C terminus only 224 3,418 residues constituting BRCA2, suggesting that these terminal amino acids crucial for function. A series green fluorescent (GFP)-tagged mutants revealed nuclear localization depends on two signals reside within final 156 BRCA2. Consistent with this observation, an endogenous...
Abstract Background The prescence of circulating tumor cells (CTCs) in the peripheral blood cancer patients and their frequency has been correlated with disease status. Methods In this study, CTCs were characterized by flow cytometry fluorescence microscopy after immunomagnetic enrichment from 7.5‐ml samples collected prostate evacuated blood‐draw tubes that contained an anticoagulant a preservative. Events classified as cell candidates if they expressed cytokeratin, lacked CD45, stained...
Compared with heart failure (HF) care 20 to 30 years ago, there has been tremendous advancement in therapy for ambulatory HF reduced ejection fraction the use of agents that block maladaptive neurohormonal pathways. However, during past decade, few notable exceptions, frequency successful drug development programs fallen as most novel therapies have failed offer incremental benefit or raised safety concerns (ie, hypotension). Moreover, no approved specifically preserved worsening chronic...
Increasing HDL levels is a potential strategy for the treatment of atherosclerosis.ITX5061, molecule initially characterized as p38 MAPK inhibitor, increased HDL-C by 20% in human population hypertriglyceridemic subjects with low levels. ITX5061 also moderately apoA-I but did not affect VLDL/LDL cholesterol or plasma triglyceride concentrations. WT and transgenic mice, kinetic experiments showed that decreased fractional catabolic rate HDL-CE reduced its hepatic uptake. In transfected cells,...
Abstract NOTCH plays a pivotal role during normal development and in congenital disorders cancer. γ-secretase inhibitors are commonly used to probe function, but also block processing of numerous other proteins. We discovered new class small molecule inhibitor that disrupts the interaction between RBPJ, which is main transcriptional effector signaling. RBPJ Inhibitor-1 ( RIN1 ) blocked functional with SHARP, scaffold protein forms repressor complex absence induced changes gene expression...
Glucocorticoids are commonly used antiinflammatory agents whose use is limited by side effects. We have developed a series of glucocorticoid receptor (GR) ligands that retain the strong activity conventional glucocorticoids with reduced present compound, LGD5552, binds efficiently and strongly represses inflammatory gene expression. LGD5552 bound to GR activates expression somewhat differently than glucocorticoids. It some genes an efficacy similar However, other glucocorticoid-activated not...
Abstract RRx-001 is currently in a phase III clinical trial for small cell lung cancer and showed activity II colorectal cancer. It has negligible side effects so could be used combination regimens with low risk of additive toxicity. multiple mechanisms action including binding to hemoglobin alter red blood (RBC) properties, increasing RBC adhesion the endothelium membrane phosphatidyl serine exposure. Importantly, RRx-001-treated RBCs are known preferentially localize solid tumors. Existing...
We have previously reported that the fractalkine (FKN)/CX3CR1 system represents a novel regulatory mechanism for insulin secretion and β cell function. Here, we demonstrate chronic administration of long-acting form FKN, FKN-Fc, can exert durable effects to improve glucose tolerance with increased glucose-stimulated decreased apoptosis in obese rodent models. Unexpectedly, FKN-Fc also led α glucagon secretion. In islet cells, FKN inhibited ATP-sensitive potassium channel conductance by an...
Atherosclerosis is a major cause of cardiovascular disease. Monocyte-endothelial cell interactions are partly mediated by expression monocyte CX3CR1 and endothelial fractalkine (CX3CL1). Interrupting the interaction between this ligand–receptor pair should reduce binding to wall atherosclerosis. We sought atherosclerosis preventing monocyte-endothelial through use long-acting agonist. In study, chemokine domain CX3CL1 was fused mouse Fc region generate soluble form suitable for chronic...
Antitumor effects of the toll-like receptor 7 (TLR7) agonist, 852A, were evaluated. Supernatants from human peripheral blood mononuclear cells (PBMC) stimulated with 852A inhibited proliferation tumor cell lines Hs294T and 769-P but had no effect on others (786-O Caki-1). Because addition directly to did not inhibit their proliferation, mechanism(s) inhibition was investigated. Low nanomolar concentrations production interferon-alpha (IFN-alpha), IFN-inducible protein-10 (IP-10),...
The stereochemistry of base-catalyzed H/D exchange on 13 β-substituted ethyl butanoates in ethanol-d has been studied order to analyze the steric and electronic factors which control diastereoselectivity electrophilic attack enolate anions. Electrophilic deuteration anion also determines stereoselectivity 1,4-conjugate addition α,β-unsaturated esters. Experimental conditions were selected rigorously exclude effects ion pairing aggregation. research showed that stereoelectronic generally...