- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Immune Cell Function and Interaction
- Arsenic contamination and mitigation
- Heavy Metal Exposure and Toxicity
- Traumatic Brain Injury and Neurovascular Disturbances
- Immune Response and Inflammation
- Acute Ischemic Stroke Management
- T-cell and B-cell Immunology
- Melanoma and MAPK Pathways
- RNA Research and Splicing
- Protein Tyrosine Phosphatases
- NF-κB Signaling Pathways
- Pancreatic and Hepatic Oncology Research
- Reproductive System and Pregnancy
- PI3K/AKT/mTOR signaling in cancer
- Pancreatitis Pathology and Treatment
- RNA regulation and disease
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- Retinoids in leukemia and cellular processes
- Traumatic Brain Injury Research
- Immune cells in cancer
- Influenza Virus Research Studies
New York University
2015-2024
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2021-2024
Medical Research Council
1976-2023
United States Air Force Academy
2023
MRC Laboratory for Molecular Cell Biology
2023
University College London
2023
Sigma Research (United States)
2023
Indiana University School of Medicine
2021
University of Regensburg
2020
Columbia University
2009-2019
The STAT1 transcription factor is activated in response to many cytokines and growth factors. To study the requirement for vivo, we disrupted Stat1 gene embryonic stem (ES) cells mice. Stat1−/− ES were unresponsive interferon (IFN), but retained responsiveness leukemia inhibitory (LIF) remained LIF dependent undifferentiated growth. animals born at normal frequencies displayed no gross developmental defects. However, these failed thrive extremely susceptible viral disease. Cells tissues from...
Abstract The accumulation of myeloid suppressor cells (MSCs) is associated with immune suppression in tumor-bearing mice and cancer patients. suppressive activity MSC correlates the expression markers Gr-1, CD115 (macrophage colony-stimulating factor receptor), F4/80. Gr-1+CD115+ MSCs, addition to being able suppress T-cell proliferation vitro, can induce development Foxp3+ T regulatory (Treg) vivo, which are anergic suppressive. Furthermore, secretion interleukin (IL)-10 transforming growth...
Exposure to manganese via inhalation has long been known elicit neurotoxicity in adults, but little is about possible consequences of exposure drinking water. In this study, we report results a cross-sectional investigation intellectual function 142 10-year-old children Araihazar, Bangladesh, who had consuming tube-well water with an average concentration 793 μg Mn/L and 3 arsenic/L. Children mothers came our field clinic, where received medical examination which weight, height, head...
The NS1 protein is the only nonstructural encoded by influenza A virus. It has been proposed that performs several regulatory functions during viral replication cycle, including regulation of synthesis, transport, splicing, and translation mRNAs. Through use reverse genetics, a viable transfectant virus (delNS1) which lacks gene generated. Our results indicate an auxiliary (virulence) factor plays crucial role in inhibiting interferon-mediated antiviral responses host.
Ras, STAT3, and Transformation The STAT (signal transducer activator of transcription) proteins are activated in response to receptor stimulation act the nucleus regulate gene expression. Gough et al. (p. 1713 ) found that STAT3 functioned transformation cells by oncogene Ras. However, this activity was maintained mutants fail activate transcription. Instead, active appeared be associated with mitochondria. Furthermore, modified targeted mitochondria promoted mitochondrial function disrupted...
Human alpha- and beta-interferons (IFNs) stimulate rapid but transient increases in transcription from a set of previously quiescent genes. Protein synthesis is not required for initial stimulation, duration the response limited to few hours by process requiring new proteins. An IFN-stimulated element (ISRE) was identified 5' an inducible gene deletion analysis point mutagenesis, sequence comparisons with other promoters defined consensus YAGTTTC(A/T)YTTTYCC. Two classes IFN-inducible...
Thrombolytic agents hold theoretical promise as therapy for cerebral infarction. This study was designed to evaluate the safety of tissue plasminogen activator, accomplish urgent patient treatment, and estimate potential efficacy activator. Following neurological evaluation computed tomography brain, patients with acute ischemic stroke were evaluated treated intravenous activator under an open-label, dose-escalation design within 90 minutes from symptom onset. End points examined included...
Abstract Progressive brain damage after transient cerebral ischemia may be related to changes in postischemic blood flow and metabolism. Regional (rCBF) glucose utilization (rCGU) were measured adult rats prior to, during (only rCBF), serially forebrain ischemia. Animals subjected 30 minutes of by occluding both common carotid arteries 24 hours cauterizing the vertebral arteries. CBF was indicator‐fractionation technique using 4‐iodo‐[ 14 C]‐antipyrine. CGU 2‐[ C]deoxyglucose method. The...
Abstract IL-17-secreting CD4+ T cells are critically involved in inflammatory immune responses. Development of these is promoted vivo and vitro by IL-23 or TGFβ1 plus IL-6. Despite growing interest this Th subset, little known about the transcription factors that required for their development. We demonstrate Stat3 programming IL-6 IL-23-stimulated phenotype, as well RORγt expression IL-6-primed cells. Moreover, retroviral transduction a constitutively active into differentiating cell...
Foxp3, a winged-helix family transcription factor, serves as the master switch for CD4(+) regulatory T cells (Treg). We identified unique and evolutionarily conserved CpG-rich island of Foxp3 nonintronic upstream enhancer discovered that specific site within it was unmethylated in natural Treg (nTreg) but heavily methylated naive cells, activated peripheral TGFbeta-induced which bound by DNMT1, DNMT3b, MeCP2, MBD2. Demethylation this CpG using DNA methyltransferase inhibitor...
The signal transduction pathway through which interferon-alpha (IFN alpha) stimulates transcription of a defined set genes involves activation DNA-binding factors specific for the IFN alpha-stimulated response element (ISRE). IFN-stimulated gene factor-3 (ISGF3), positive regulator transcription, was derived in to alpha treatment from preexisting protein components that were activated first cell cytoplasm prior appearance nucleus. Nuclear translocation ISGF3 required several minutes and...
Interferon-stimulated gene factor 3 (ISGF3) is the ligand-dependent transcriptional activator that, in response to interferon treatment, assembled cell cytoplasm, translocated nucleus, and binds consensus DNA site, interferon-stimulated element. We have purified ISGF3 identified its constituent proteins: a DNA-binding protein of 48 kDa three larger polypeptides (84, 91, 113 kDa), which themselves do not activity. The multisubunit structure most likely reflects participation receiving signal,...
Outcome from coma caused by cerebral hypoxia-ischemia (eg, cardiac arrest) was compared with serial neurological findings in 210 patients. Thirteen percent of patients regained independent function at some point during the first postarrest year. Computer application new multivariate techniques to prospectively observed generated easily utilized rules that classified likely outcome. At time initial examination, 52 (one fourth total population) had absent pupillary light reflexes, and none...
<b>Objective</b> To evaluate the association between arsenic exposure and mortality from cardiovascular disease to assess whether cigarette smoking influences association. <b>Design</b> Prospective cohort study with measured in drinking water wells urine. <b>Setting</b> General population Araihazar, Bangladesh. <b>Participants</b> 11 746 men women who provided urine samples 2000 were followed up for an average of 6.6 years. <b>Main outcome measure</b> Death disease. <b>Results</b> 198 people...
Propagation of mouse embryonic stem (ES) cells in vitro requires exogenous leukemia inhibitory factor (LIF) or related cytokines. Potential downstream effectors the LIF signal ES include kinases Src, Jak, and mitogen-activated protein families transducer transcriptional activator STAT3. Activation nuclear STAT3 ability to grow as undifferentiated clones were monitored during withdrawal. A correlation was found between levels activity maintenance an phenotype at clonal density. In contrast,...