A5009333157- Antibiotic Resistance in Bacteria
- Tuberous Sclerosis Complex Research
- Protein Structure and Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Histiocytic Disorders and Treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Complement system in diseases
- Venous Thromboembolism Diagnosis and Management
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Medical Imaging and Pathology Studies
- Lymphoma Diagnosis and Treatment
- Nuclear Receptors and Signaling
- Cholesterol and Lipid Metabolism
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- Pneumocystis jirovecii pneumonia detection and treatment
- Glycosylation and Glycoproteins Research
- Mast cells and histamine
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Hematopoietic Stem Cell Transplantation
- RNA Interference and Gene Delivery
- Nuclear reactor physics and engineering
- thermodynamics and calorimetric analyses
- Ubiquitin and proteasome pathways
National Heart Lung and Blood Institute
2007-2021
National Institutes of Health
2006-2021
Johns Hopkins University
2004
Lung Institute
2001
University of Connecticut
1992
UConn Health
1990
Murine leukemia virus (MLV)-derived vectors are widely used for hematopoietic stem cell (HSC) gene transfer, but lentiviral such as the simian immunodeficiency (SIV) may allow higher efficiency transfer and better expression. Recent studies in lines have challenged notion that retroviruses retroviral integrate randomly into their host genome. Medical applications using these aimed at HSCs, thus large-scale comprehensive analysis of MLV SIV integration long-term repopulating HSCs is crucial...
Two new techniques for modeling chemical processes in condensed phases with combined quantum mechanical and molecular (QM/MM) potentials are introduced tested on small, model compounds. The first technique, the double link atom (DLA) method, is an extension of traditional, single (SLA) method to avoid some problems latter method. These primarily electrostatic, as SLA can produce unphysical overall charge or dipole. second delocalized Gaussian MM (DGMM) empirical way include character...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystallographic Structure of a Phosphonate Derivative the Enterobacter cloacae P99 Cephalosporinase: Mechanistic Interpretation .beta.-Lactamase Transition-State AnalogEmil Lobkovsky, Eric M. Billings, Paul C. Moews, Jubrail Rahil, R. F. Pratt, and James KnoxCite this: Biochemistry 1994, 33, 22, 6762–6772Publication Date (Print):June 7, 1994Publication History Published online1 May 2002Published inissue 7 June...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInactivation of class A .beta.-lactamases by clavulanic acid: the role arginine-244 in a proposed nonconcerted sequence eventsUzma Imtiaz, Eric Billings, James R. Knox, Elias K. Manavathu, Stephen A. Lerner, and Shahriar MobasheryCite this: J. Am. Chem. Soc. 1993, 115, 11, 4435–4442Publication Date (Print):June 1, 1993Publication History Published online1 May 2002Published inissue 1 June...
Abstract The potential for therapeutic specificity in regulating diseases and reduced side effects has made cannabinoid (CB) receptors one of the most important G‐protein‐coupled receptor (GPCR) targets drug discovery. subtype CB2 is particular interest due to its involvement signal transduction immune system increased characterization by mutational other studies. However, our understanding their mode action been limited absence an experimental structure. In this study, we have developed a...
Mammalian target of rapamycin (mTOR) and phosphatidylinositol 3-kinase (PI3K) regulate cell growth, protein synthesis, apoptosis in response to nutrients mitogens. As an important source nitric oxide during inflammation, human inducible synthase also plays a role the regulation cytokine-driven proliferation apoptosis. The mTOR PI3K activation transcription by cytokines lipopolysaccharide (LPS) was investigated lung epithelial adenocarcinoma (A549) cells. LY294002, dual inhibitor, blocked...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Structure-Based Analysis of the Inhibition Class A .beta.-Lactamases by SulbactamUzma Imtiaz, Eric M. Billings, James R. Knox, and Shahriar MobasheryCite this: Biochemistry 1994, 33, 19, 5728–5738Publication Date (Print):May 17, 1994Publication History Published online1 May 2002Published inissue 17 1994https://doi.org/10.1021/bi00185a009RIGHTS & PERMISSIONSArticle Views326Altmetric-Citations67LEARN ABOUT THESE METRICSArticle Views are...
The identification of ABCA1 as a key transporter responsible for cellular lipid efflux has led to considerable interest in defining its role cholesterol metabolism and atherosclerosis. In this study, the effect overexpressing liver LDLr-KO mice was investigated. Compared with mice, ABCA1-Tg × (ABCA1-Tg) had significantly increased plasma levels, mostly because 2.8-fold increase associated large pool apoB-lipoproteins. ApoB synthesis unchanged but catabolism 125I-apoB-VLDL -LDL were delayed,...
Alveolar transforming growth factor (TGF)-β1 signaling and expression of TGF-β1 target genes are increased in patients with idiopathic pulmonary fibrosis (IPF) animal models fibrosis. Internalization degradation TGF-β receptor TβRI inhibits could attenuate development experimental lung fibrosis.To demonstrate that after injury, human syndecan-2 confers antifibrotic effects by inhibiting alveolar epithelial cells.Microarray assays were performed to identify differentially expressed...
Abstract Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused LAM cells (smooth-muscle-like cells) that have mutations in the tumor suppressor genes tuberous sclerosis complex (TSC) 1 or 2 and capacity to metastasize. Since chemokines their receptors function chemotaxis of metastatic cells, we hypothesized may be recruited chemokine(s) lung. Quantification 25 bronchoalveolar lavage fluid from patients healthy volunteers revealed concentrations CCL2, CXCL1, CXCL5...
Patients with tuberous sclerosis complex (TSC) develop hamartomas containing biallelic inactivating mutations in either TSC1 or TSC2, resulting mammalian target of rapamycin (mTOR) activation. Hamartomas overgrow epithelial and mesenchymal cells TSC skin. The pathogenetic mechanisms for these changes had not been investigated, the existence location ("two-hit" cells) was unclear. We compared skin (angiofibromas periungual fibromas) normal-appearing same patient, we observed more...
Abstract Activation of inflammation in white adipose tissue (WAT), includes infiltration/expansion WAT macrophages, contributes pathogenesis obesity, insulin resistance and metabolic syndrome. The inflammasome comprises an intracellular sensor (NLR), caspase-1 the adaptor ASC. Inflammasome activation leads to maturation processing IL1β, contributing many disorders directing adipocytes a more insulin-resistant phenotype. Ablation PDE3B prevents by reducing expression NLRP3, caspase-1, ASC,...
Site-saturation mutagenesis was performed on the class A ROB-1 beta-lactamase at conserved Ser130, which is centrally located in antibiotic binding site where it can participate both protein-protein and protein-substrate hydrogen bonding. Mutation Thr130 gave a hydrolysing penicillins cephalosporins but showed 3-fold lower affinity (Km) for ampicillin cephalexin, 30-fold hydrolytic (Vmax) activity ampicillin. In contrast, cephalexin similar to wild-type mutation. Gly130 only with an...
in-stent restenosis is a major limitation of stent therapy for atherosclerosis coronary artery disease. The CardioGene Study an ongoing study in bare mental stents (BMS) the treatment overall goal to understand genetic determinants responses vascular injury that result development some patients but not others. Gene expression profiling at transcriptional and translational levels provides global assessment gene activity after mechanistic insight. Furthermore, delineation biomarkers would be...
Rationale: Alveolar macrophages are inflammatory cells that may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is characterized by excessive alveolar aggregation and extracellular matrix proteins.Objectives: To identify potential molecular mechanisms IPF.Methods: examine large-scale gene expression, messenger RNA isolated from peripheral blood mononuclear subjects with IPF normal volunteers was hybridized cDNA filters.Measurements Main Results: We showed in...
BackgroundAvailable blood assays for venous thromboembolism (VTE) suffer from diminished specificity. Compared with single marker tests, such as D-dimer, a multi-marker strategy may improve diagnostic ability. We used direct mass spectrometry (MS) analysis of serum patients VTE to determine whether protein expression profiles would predict diagnosis.Methods and ResultsWe developed MS computational approach the proteomic serum. Using this new method, we analyzed inpatients undergoing...
Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG)2 activates ADP-ribosylation factors, ∼20-kDa GTPase proteins critical for continuity of intracellular vesicular trafficking by accelerating the replacement factor-bound GDP with GTP. Mechanisms additional BIG2 function(s) are less clear. Here, participation in integrin β1 cycling through actin dynamics during cell migration was identified using small interfering RNA (siRNA) and difference gel electrophoresis analyses. After a...
The vascular disease in-stent restenosis (ISR) is characterized by formation of neointima and adverse inward remodeling the artery after injury coronary stent implantation. We hypothesized that analysis gene expression in peripheral blood mononuclear cells (PBMCs) would demonstrate differences transcript between individuals who develop ISR those do not.We determined investigated PBMC 358 patients undergoing an index procedure to treat de novo lesions with bare metallic stents, using a novel...