A5073105949- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- Estrogen and related hormone effects
- Ion Transport and Channel Regulation
- Cholesterol and Lipid Metabolism
- Cancer-related gene regulation
- Protease and Inhibitor Mechanisms
- Angiogenesis and VEGF in Cancer
- Cytokine Signaling Pathways and Interactions
- Lipoproteins and Cardiovascular Health
- Atherosclerosis and Cardiovascular Diseases
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Magnesium in Health and Disease
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cellular Mechanics and Interactions
- Ubiquitin and proteasome pathways
- Blood Coagulation and Thrombosis Mechanisms
- Tracheal and airway disorders
- Cancer, Lipids, and Metabolism
- Molecular Biology Techniques and Applications
- Cardiovascular Disease and Adiposity
Beth Israel Deaconess Medical Center
2011-2024
Harvard University
2008-2024
Center for Vascular Biology Research
2009-2024
Beth Israel Deaconess Hospital
1992-2024
Hadassah Medical Center
2007-2015
Massachusetts Institute of Technology
2005-2012
Research Institute for Chromatography
2012
KU Leuven
2012
Boston University
2012
Sidney Kimmel Cancer Center
2012
Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who a response to anilinoquinazoline EGFR inhibitors. Despite dramatic responses such inhibitors, most ultimately relapse. The mechanism drug resistance is unknown. Here we report case patient EGFR-mutant, gefitinib-responsive, advanced had relapse after two years complete remission during treatment gefitinib. DNA sequence his tumor biopsy specimen at...
Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that hyperplastic epidermis of psoriatic expresses strikingly increased amounts vascular permeability factor (VPF; endothelial growth factor), a selective cell mitogen enhances permeability. Moreover, two VPF receptors, kdr flt-1, overexpressed papillary dermal cells. Transforming alpha (TGF-alpha), cytokine also in epidermis, induced gene...
The epithelial anion channel CFTR interacts with multiple PDZ domain-containing proteins. Heterologous expression studies have demonstrated that the Na+/H+ exchanger regulatory factors, NHERF1, NHERF2, and PDZK1 (NHERF3), modulate membrane retention, conductivity, interactions other transporters. To study their biological roles in vivo, we investigated CFTR-dependent duodenal HCO3- secretion mouse models of Nherf1, Nherf2, Pdzk1 loss function. We found Nherf1 ablation strongly reduced basal...
Actin of smooth muscle cells rat and human aortic media shows a predominance the alpha-isoform. In experimental intimal thickening, in atheromatous plaque, cultured cells, there is typical switch actin expression with beta-form noticeable amount gamma-form. This pattern represents new reliable protein-chemical marker cells.
Context.—Zafirlukast is a potent leukotriene antagonist that recently was approved for the treatment of asthma. As use this drug increases, adverse events occur at low frequency or in populations not studied premarketing clinical trials may become evident.Objective.—To describe syndrome associated with zafirlukast therapy.Design.—Case series.Patients.—Eight adults (7 women and 1 man) steroid-dependent asthma who received zafirlukast.Main Outcome Measures.—Development characterized by...
ABSTRACT VPF/VEGF acts selectively on the vascular endothelium to enhance permeability, induce cell migration and division, delay replicative senescence. To understand changes in gene expression during endothelial senescence, we investigated genes that were differentially expressed early vs. late passage (senescent) human dermal cells (HDMEC) using cDNA array hybridization. Early HDMEC cultured with or without overexpressed 9 underexpressed 6 comparison their senescent counterparts. Thymosin...
Abstract Transforming growth factor‐beta 1 (TGF‐β ) is angiogenic in vivo. In two‐dimensional (2‐D) culture systems microvascular endothelial cell proliferation inhibited up to 80% by TGF‐β however, three‐dimensional (3‐D) collagen gels found have no effect on while eliciting the formation of calcium and magnesium dependent tube‐like structures mimicking angiogenesis. DNA analyses performed 3‐D cultures reveal significant difference amount or number control versus treated cultures. 2‐D known...
To investigate a possible correlation between cytodifferentiation, proliferation, and actin expression, smooth muscle cells from the 9-week-old rabbit aortic media were enzyme-dispersed into single plated in primary culture at different initial seeding densities. The volume fraction of myofilaments (Vv myo) seeded moderately densely fell 39.5% +/- 1.2% intact to 11.5% 1.6% on Day 5, one day before onset logarithmic growth. Vv myo remained low over next 3 days, then began rise as density...
Cytomegalovirus (CMV) infection is a common in adults (seropositive 60–99% globally), and associated with cardiovascular diseases, line risk factors such as hypertension atherosclerosis. Several viral infections are linked to hypertension, including human herpes virus 8 (HHV-8) HIV-1. The mechanisms of how contributes or increased blood pressure not defined. In this report, the role CMV cause forming aortic atherosclerotic plaques examined. Using vivo mouse model vitro molecular biology...
Actin, vimentin, desmin, and tropomyosin distribution in rat aortic endothelial smooth muscle cells has been studied during development using fetal (18 to 20 days of gestation), 5- 14-day-, 5-, 12-week-old rats. Endothelial newborn animals actively replicate contain many actin stress fibers, whereas, adult animals, replication is minimal fibers are rare. The actin, content increases gradually from animals. number desmin-containing also 13% rats 51% beta-actin isoform predominant but the...
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation sustain survival signals. In this report, we describe novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation the fatty acid synthase (FASN), which produces 16-C saturated palmitate. Our work shows that persistent by...
Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture erosion of unstable atherosclerotic plaques are leading cause death worldwide. Although most mouse models atherosclerosis develop lesions in aorta and carotid arteries, they do not advanced coronary artery lesions. Moreover, undergo spontaneous plaque with MI stroke so at such a low frequency that viable experimental to study late-stage thrombotic events identify novel therapeutic approaches for...
PDZK1, a multi-PDZ domain containing adaptor protein, interacts with various membrane proteins, including the high density lipoprotein (HDL) receptor scavenger class B type I (SR-BI). Here we show that PDZK1 controls in tissue-specific and post-transcriptional fashion expression of SR-BI vivo. protein knock-out (KO) mice was reduced by 95% liver, 50% proximal intestine, not affected steroidogenic organs (adrenal, ovary, testis). Thus, joins growing list adaptors control activity cell surface...
Quiescent smooth muscle cells (SMC) in normal artery express a pattern of actin isoforms with alpha-smooth (alpha SM) predominance that switches to beta when the are proliferating. We have examined relationship between change and entry SMC into growth cycle an vivo model proliferation (balloon injured rat carotid artery). alpha SM mRNA declined cytoplasmic (beta + gamma) mRNAs increased early G0/G1 (between 1 8 h after injury). In synthesis vitro translation experiments demonstrated...
Untreated and long-lasting obstructive sleep apnea (OSA) may lead to important vascular abnormalities, including endothelial cell (EC) dysfunction, hypertension, atherosclerosis. We observed a correlation between microcirculatory reactivity endothelium-dependent release of nitric oxide in OSA patients. Therefore, we hypothesized that affects (micro)vasculature aimed identify gene targets could possibly serve as reliable biomarkers severity the disease risk. Using quantitative RT-PCR,...