A5100655430- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Nitric Oxide and Endothelin Effects
- Ion Channels and Receptors
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Organ Transplantation Techniques and Outcomes
- Ion Transport and Channel Regulation
- Lung Cancer Treatments and Mutations
- Neuroscience of respiration and sleep
- Orthopedic Surgery and Rehabilitation
- Cardiac Ischemia and Reperfusion
- Pulmonary Hypertension Research and Treatments
- Lymphoma Diagnosis and Treatment
- Calcium signaling and nucleotide metabolism
- Receptor Mechanisms and Signaling
- Cardiomyopathy and Myosin Studies
- Inflammasome and immune disorders
- Educational Research and Pedagogy
- Elbow and Forearm Trauma Treatment
- Immune Cell Function and Interaction
- Shoulder Injury and Treatment
- Renin-Angiotensin System Studies
- Nicotinic Acetylcholine Receptors Study
- Cardiovascular Function and Risk Factors
University of Kansas
2005-2025
Argonne National Laboratory
2025
Seoul National University
2015-2024
New Generation University College
2012-2024
Rutgers Cancer Institute of New Jersey
2024
Apple (United States)
2024
Cancer Institute of Florida
2024
Genomics Institute of the Novartis Research Foundation
2006-2023
Samsung Medical Center
2010-2023
Sungkyunkwan University
2010-2023
Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine inhibitor (TKI) crizotinib. Herein, we report first preclinical evaluation of next-generation TKI, ceritinib (LDK378), in setting crizotinib resistance. An interrogation vitro and vivo models acquired crizotinib, including lines established from biopsies patients with crizotinib-resistant NSCLC, revealed that potently overcomes mutations. In...
The synthesis, preclinical profile, and in vivo efficacy rat xenograft models of the novel selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) described as well rational design strategy employed to overcome development deficiencies first generation ALK 4 (TAE684). Compound is currently phase 1 2 clinical trials with substantial antitumor activity being observed ALK-positive cancer patients.
Constitutive overexpression and activation of NPM-ALK fusion protein [t(2:5)(p23;q35)] is a key oncogenic event that drives the survival proliferation anaplastic large-cell lymphomas (ALCLs). We have identified highly potent selective small-molecule ALK inhibitor, NVP-TAE684, which blocked growth ALCL-derived ALK-dependent cell lines with IC(50) values between 2 10 nM. NVP-TAE684 treatment resulted in rapid sustained inhibition phosphorylation its downstream effectors subsequent induction...
Long-term integration of neuroprosthetic devices is challenged by reactive responses that compromise the brain–device interface. The contribution physical insertion parameters to immediate damage not well described. We have developed an ex vivo preparation capture real-time images tissue deformation during device using thick slices from rat brains prepared with fluorescently labeled vasculature. Qualitative and quantitative assessments were made for insertions different tip shapes inserted...
Alms and methods The association between body mass index (BMI) blood pressure is well known in relatively obese populations. purpose of the present study was to investigate relationship BMI a lean population. Through cluster sampling, individuals aged >30 years 190 out 154 082 districts were selected for study. Among 25 567 eligible individuals, measurements made 22 354. Results males 22.8 ± 2.7kg/m2 females 23.4 3.2 kg/m2 (means SD). Over range from 16 31 relationships systolic diastolic...
Rapid quantitative methods for characterizing small molecules, peptides, proteins, or RNAs in a broad array of cellular assays would allow one to discover new biological activities associated with these molecules and also provide more comprehensive profile drug candidates early the development process. Here we describe robotic system, termed automated compound profiler, capable both propagating large number cell lines parallel assaying collections simultaneously against matrix highly...
Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig-to-nonhuman primate (NHP) model has not been demonstrated. Here, we report that pig grafts survived and maintained normoglycemia >6 months four of five consecutive immunosuppressed NHPs. were isolated from designated pathogen-free (DPF) miniature pigs infused intraportally into streptozotocin-induced diabetic rhesus monkeys under pretreatment with...
ALK (anaplastic lymphoma kinase) is an RTK (receptor tyrosine of the IRK (insulin receptor superfamily, which share YXXXYY autophosphorylation motif within their A-loops (activation loops). A common activation and regulatory mechanism believed to exist for members this superfamily typified by IGF1RK (insulin-like growth factor kinase-1). Chromosomal translocations involving were first identified in anaplastic large-cell lymphoma, a subtype non-Hodgkin's where aberrant fusion kinase domain...
The implantable cardioverter-defibrillator (ICD) is an effective method to prevent sudden cardiac death in high-risk patients. However, the transvenous lead incompatible with large-area electrophysiological mapping and cannot accommodate selective multichannel precision stimulations. Moreover, it involves high-energy shocks, resulting pain, myocardial damage, recurrences of ventricular tachyarrhythmia (VTA). We present a for VTA treatment based on subthreshold electrical stimulations using...
Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches non-clinical animal research. However, most of these struggle accurately replicate adult human heart conditions, such infarction ventricular remodeling pathology. The intricate interplay between various cell types within the heart, including cardiomyocytes, fibroblasts, endothelial cells, contributes...
Bmi-1 is a polycomb group protein that was identified as c-myc cooperating oncogene in murine lymphomagenesis. The current study undertaken to determine the role of human oral carcinogenesis. and RNA expression levels were markedly enhanced cells squamous cell carcinomas (OSCC) compared with normal keratinocytes (NHOK). Enhanced-Bmi-1 also detected situ archived mucosal tissues cancerous precancerous histopathology, including mild epithelial dysplasia. Thus, occurs at very early stage To...
The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor, and amyloid beta peptide (Abeta) one of the ligands RAGE. Because RAGE transporter Abeta from blood to brain, believed play an important role in Alzheimer's disease (AD) pathogenesis. In present study, production was examined brain tissue AD animal model, Tg2576 mice, as well cultured cells. beta-site APP-cleaving enzyme 1 (BACE1), essential protease production, up-regulated cells overexpressing...
Hypoxia-inducible factor 1α (HIF-1α) is rapidly degraded by the ubiquitin-proteasome pathway under normoxic conditions. Ubiquitination of HIF-1α mediated interaction with von Hippel-Lindau tumor suppressor protein (pVHL). In our previous report, we found that hypoxia-induced active signal transducer and activator transcription3 (STAT3) accelerated accumulation prolonged its half-life in solid cells. However, specific mechanisms are not fully understood. Thus, examined role STAT3 mechanism...
Abstract Transient receptor potential vanilloid type 1 (TRPV1) is a molecular sensor for detecting adverse stimuli, such as capsaicin, heat, and acid. TRPV1 has been localized in keratinocytes suggested to be mediator of heat‐induced matrix metalloproteinase‐1 (MMP‐1). With regard the multimodal activation TRPV1, we hypothesize that might also mediate UV‐induced MMP‐1 keratinocytes. In HaCaT, human keratinocyte cell line, initially confirmed capsaicin‐induced membrane current Ca 2+ influx....
The endoplasmic reticulum (ER) is not only a home for folding and posttranslational modifications of secretory proteins but also reservoir intracellular Ca(2+). Perturbation ER homeostasis contributes to the pathogenesis various neurodegenerative diseases, such as Alzheimer's Parkinson diseases. One key regulator that underlies cell survival Ca(2+) during stress responses inositol-requiring enzyme 1α (IRE1α). Despite extensive studies on this membrane-associated protein, little known about...
In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since considered ineffective. The role of CCRT comparison approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) such patients remains be defined.Three hundred three untreated (207 men, 96 women; median age: 51, 18-86 years) NK/T-cell lymphoma who...
Calcium ions (Ca2+), protons (H+), and borate (B(OH)4–) are essential in the control of tip growth pollen tubes. All three may interact with pectins, a major component expanding tube cell wall. Ca2+ is thought to bind acidic residues, cross‐link adjacent pectin chains, thereby strengthening Protons loosening agents; walls they act through enzyme methylesterase (PME), either reduce demethylation or stimulate hydrolysis pectin. Finally, cross‐links monomers rhamnogalacturonan II (RG‐II), thus...
Aberrant membrane transport caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with a wide spectrum of respiratory and digestive diseases as well fibrosis. Using scanning method, we found 11 polymorphisms CFTR Korean population. Individual variants at these sites were analyzed conventional DNA screening 117 control 75 patients having bronchiectasis or chronic pancreatitis. In haplotype determination based on Bayesian algorithm, 15...
To investigate polymorphisms of the VEGF gene in patients with rheumatoid arthritis (RA), their relationship to clinical features and radiographic progression joint disease.One hundred forty RA 149 healthy unrelated controls were recruited. We examined four which are reported be associated production vascular endothelial growth factor (VEGF), using polymerase chain reaction (PCR) restriction fragment length polymorphism assay amplification refractory mutation system (ARMS) PCR. Haplotypes...