A5007701898- Hemoglobinopathies and Related Disorders
- Liver physiology and pathology
- Tannin, Tannase and Anticancer Activities
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Mechanisms and Therapy
- Glutathione Transferases and Polymorphisms
- Erythrocyte Function and Pathophysiology
- Iron Metabolism and Disorders
- Chromatin Remodeling and Cancer
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Circular RNAs in diseases
- Infant Nutrition and Health
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Prenatal Screening and Diagnostics
- Microtubule and mitosis dynamics
- Neonatal Respiratory Health Research
- Drug Transport and Resistance Mechanisms
- FOXO transcription factor regulation
- Immunotherapy and Immune Responses
- Pediatric Hepatobiliary Diseases and Treatments
- Cytokine Signaling Pathways and Interactions
- Computational Drug Discovery Methods
- Melanoma and MAPK Pathways
University of Illinois Chicago
2015-2024
University of Chicago Medical Center
2005-2023
Jesse Brown VA Medical Center
2015-2018
University of Chicago
2004-2009
Cancer Research Center
2009
Immunovaccine (Canada)
2008
Roswell Park Comprehensive Cancer Center
2007
University of Minnesota
2005
University of Madras
2000-2005
Dana-Farber Cancer Institute
2004
Abstract Non–small cell lung cancer (NSCLC) is a difficult disease to treat. The c-Met receptor an attractive potential target for novel therapeutic inhibition in human cancers. We provide strong evidence that overexpressed, activated, and sometimes mutated NSCLC lines tumor tissues. Expression of was found all (100%) the tissues examined (n = 23) most (89%) 9). Sixty-one percent strongly expressed total c-Met, especially adenocarcinoma (67%). Specific expression phospho-Met (p-Met) [Y1003]...
MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many which can be dysregulated in human cancers. Activated signaling lead to cell motility scattering, angiogenesis, proliferation, branching morphogenesis, invasion, eventual metastasis. We performed systematic analysis the expression HGF tumor tissue microarrays (TMA) from solid Standard immunohistochemistry (IHC) computerized automated scoring system were used. DNA...
Recurrent/metastatic head and neck cancer remains a devastating disease with insufficient treatment options. We investigated the MET receptor tyrosine kinase as novel target for of squamous cell carcinoma (HNSCC). MET/phosphorylated HGF expression was analyzed in 121 tissues (HNSCC/normal) by immunohistochemistry, 20 HNSCC lines immunoblotting. The effects inhibition using small interfering RNA/two small-molecule inhibitors (SU11274/PF-2341066) on signaling, migration, viability,...
Abstract c-Met receptor tyrosine kinase (RTK) has not been extensively studied in malignant pleural mesothelioma (MPM). In this study, was overexpressed and activated most of the cell lines tested. Expression MPM tissues by immunohistochemistry increased (82%) general compared with normal. internalized its ligand hepatocyte growth factor (HGF) H28 cells, robust expression c-Met. Serum circulating HGF twice as high patients healthy controls. There a differential response activation AKT...
The c-MET receptor can be overexpressed, amplified, or mutated in solid tumours including small cell lung cancer (SCLC). In c-MET-overexpressing SCLC line NCI-H69, hepatocyte growth factor (HGF) dramatically induced phosphorylation at phosphoepitopes pY1230/1234/1235 (catalytic tyrosine kinase), pY1003 (juxtamembrane), and also of paxillin pY31 (CRKL-binding site). We utilised a global proteomics phosphoantibody array approach to identify further c-MET/HGF signal transduction intermediates...
Abstract Purpose: c-Met is a receptor tyrosine kinase involved in cell growth, invasion, metastases, and angiogenesis. In this study, we investigated the role of melanoma biology using novel small-molecule inhibitor SU11274 small interfering (si) RNA against receptor. Experimental Design: The effects siRNA were studied on proliferation, apoptosis, differentiation, reactive oxygen species, intracellular signaling. mutations examined, expression activated was nevi, primary, metastatic...
Abstract The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors, including lung cancer. PHA-665752 was identified small molecule, ATP competitive inhibitor of the catalytic activity kinase. Here, we show that treatment with PHA665752 reduced NCI-H69 (small cell cancer) and NCI-H441 (non–small tumorigenicity mouse xenografts by 99% 75%, respectively. Reduction tumor size also observed magnetic resonance imaging tumors mice. inhibited phosphorylation at...
Abstract Lung cancer is characterized by abnormal cell growth and invasion, the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin target of number oncogenes involved key signal transduction important motility migration. In lung tissues, we have found that was highly expressed (compared with normal lung), amplified (12.1%, 8 66) correlated increased MET epidermal factor receptor (EGFR) gene copy numbers, or mutated (somatic mutation rate 9.4%, 18...
Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. In tissue samples NEC, we identified numerous macrophages and a few neutrophils but not many lymphocytes. We hypothesized that these pathoanatomic characteristics NEC represent common injury response the gastrointestinal tract to variety insults at specific stage gut development. To evaluate developmental changes in mucosal response, used trinitrobenzene sulfonic acid (TNBS)-induced inflammation as...
Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part pathophysiology is the excessive formation intracellular reactive oxygen species (ROS) in red cells (RBCs), which accelerates their hemolysis....
To test the hypothesis that FYN, a member of SRC family kinases (SFKs), is up-regulated in prostate cancer, as FYN functionally distinct from other SFKs, and interacts with FAK paxillin (PXN), regulators cell morphology motility.Through data-mining Oncomine (http://www.oncomine.org), cell-line profiling immunoblotting, quantitative reverse transcription polymerase chain reaction (RT-PCR) immunohistochemical analysis, we described expression cancer. The analysis included 32 cases nine...
Preterm infants may be at risk of necrotizing enterocolitis (NEC) due to deficiency transforming growth factor-β 2 (TGF-β ) in the developing intestine. We hypothesized that low epithelial TGF-β expression preterm intestine and during NEC results from diminished autocrine induction these cells. Premature baboons delivered 67% gestation were treated per current norms for human infants. was diagnosed by clinical radiological findings. Inflammatory cytokines, , Smad7, Ski, strawberry notch N...
Increased fetal hemoglobin levels lessen the severity of symptoms and increase lifespan patients with sickle cell disease. Hydroxyurea, only drug currently approved for treatment disease, is not effective in a large proportion therefore new pharmacological agents that have long been sought. Recent studies identifying LSD-1 as repressor γ-globin expression led to experiments demonstrating inhibitor RN-1 increased mouse model. Because arrangement developmental stage-specific pattern β-like...
Sickle cell disease (SCD) is caused by a mutation of the β-globin gene that results in production hemoglobin S (HbS). People with SCD experience anemia, severe acute pain episodes, persistent chronic pain, multiorgan damage, and reduced life span. The pathophysiology polymerization HbS on deoxygenation red deformability generation reactive oxygen species (ROS). These 2 factors lead to fragility hemolysis. Reticulocytosis an independent predictor morbidity mortality SCD. We previously...
Using mass spectrometric analysis we found that oncogenic transcription factor FOXM1 is overexpressed in a majority of human cancers interacts with multifunctional protein NPM, which also variety tumors. Coimmunoprecipitation and glutathione S-transferase pull-down experiments demonstrated NPM forms complex identified the regions responsible for their interaction. Immunofluorescence microscopy confirmed interaction between cancer immortal cells. Furthermore, knockdown cells led to...
Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a key role in gut mucosal development. Preterm birth interrupts this exposure to fluid-borne possibly contributing the increased risk necrotizing enterocolitis (NEC) premature infants. We hypothesized that supplementation formula feeds with fluid can provide factors prevent experimental NEC rat pups. compared NEC-like injury pups fed infant vs. supplemented either 30% or recombinant hepatocyte...
Small cell lung cancer (SCLC) is a difficult disease to treat and sometimes has overexpression or mutation of c-Met receptor tyrosine kinase. The effects c-Met/hepatocyte growth factor (c-Met/HGF, ligand for c-Met) on activation reactive oxygen species (ROS) was determined. HGF stimulation c-Met-overexpressing H69 SCLC cells (40 ng/ml, 15 min) resulted in an increase ROS, measured with fluorescent probe 2'-7'-dichlorofluorescein diacetate (DCFH-DA) dihydroethidine (DHE) but not c-Met-null...
Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis premature infants. In this study we hypothesized infants remain at higher risk NEC than full-term infants, even when they receive their own mother's milk, because preterm human less bioactive TGF-β milk. Our objective was...
Abstract Increased fetal hemoglobin (HbF) levels reduce the symptoms of sickle cell disease (SCD) and increase lifespan patients. Because curative strategies for bone marrow transplantation gene therapy technologies remain unavailable to a large number patients, development safe effective pharmacological that increases HbF offers greatest potential intervention. Although hydroxyurea HbF, substantial proportion patients fail demonstrate an adequate response. Pharmacological inhibitors DNA...
AbstractCancers typically harbour several mutant forms of key cellular genes that contribute to its complex phenotype. Our lab has previously identified gain-of-function mutations in some the receptor tyrosine kinases such as c-Met lung cancer. In order investigate gene context a whole organism, current choice vivo model is limited mouse. To rapidly screen functional aspects detected cancer, we used nematode C. elegans organism. Transgenic worms were generated wild type or frequently seen...
Neonates and young infants exposed to extracorporeal circulation during membrane oxygenation (ECMO) cardiopulmonary bypass are at risk of developing a systemic inflammatory response syndrome with multi-organ dysfunction. We used piglet model ECMO investigate the hypothesis that epithelial apoptosis is an early event precedes villous damage ECMO-related bowel injury. Healthy 3-week-old piglets were subjected for up 8 h. Epithelial was measured in histopathological analysis, nuclear imaging,...
Objective We have shown previously that preterm infants are at risk of necrotizing enterocolitis (NEC), an inflammatory bowel necrosis typically seen in born prior to 32 weeks' gestation, because the developmental deficiency transforming growth factor (TGF)-β2 intestine. The present study was designed investigate all-trans retinoic acid (atRA) as inducer TGF-β2 intestinal epithelial cells (IECs) and elucidate involved signaling mechanisms. Methods AtRA effects on epithelium were investigated...