Laboratories
- Laboratories
- Cell Pharmacology. Genomics and Gene Regulation
- Biopathology and Pharmacology of Inflammation
- Molecular Biology and Gene Regulation
- Adult and Embryonic Stem Cell Biology
-
Fetal and Adult Stem Cell Therapy
- Lipidomics and Atherosclerosis
- Vascular Cell Proteomics
-
Vascular Biopathology and Molecular Genetics
Major position and appointments
Senior investigator
PhD Supervisor in Cellular and Molecular Biology
Advisor graduate and master thesis program
Member of the Scientific Council
Research Fellow, Fulbright Fellowship Yale Univ.,
Expert in Romanian Committee FP7 Health Programme
Evaluator at the Romanian Research Programs and international journalsMajor research interests
Histamine receptors of the microvascular endothelium
Spectrin and fodrin-like proteins in endothelial cells
Transport of plasma hormones and macromolecules through endothelial cells
Protein and lipid composition of the membrane microdomains of endothelial cells
Gene polymorphisms in atherosclerosis, diabetes mellitus, obesity, metabolic syndrome and ageing
Role of endothelin and nitric oxide in diseases characterized by endothelial dysfunction
Lysosomal enzymes in cells involved in atherosclerosis
Junctional proteins at the endothelial cell-cell contactTechnical expertise
Cell biology methods: experimental animals, cell culture (endothelial cells, smooth muscle cells), microscopy (optic, fluorescence and electron microscopy), immunocyto-chemistry, protein labeling, scintillation counting, autoradiography, immunochemical methods, western blotting, DNA and protein electrophoresis, gel and affinity chromatography, spectrophotometry and spectrofluorimetry; Molecular biology methods: nucleic acids isolation and purification, PCR, RFLP-PCR, quantitative Real Time PCR, gene cloning, plasmid constructs, DNA and silencing RNA transfection, decoy oligodeoxynucleotides, transcription factor analysis (chromatin immunoprecipitation).
Publications
53 original scientific articles, 4 book chapters - ISI citations: 335
Previous projects
Microvascular endothelium exibits histamine receptors
Histamine plays an important role in a number of physiological and pathological processes; it is implicated in inflammatory reactions by a process mediated by H1 and H2 receptors.
Spectrin and Fodrin-like proteins in endothelial cellsWe demonstrated the presence of histamine receptors on the luminal plasmalemma of endothelial cell by electron microscopy using histamine-ferritin complex. The distribution of the receptors is uneven along the microvasculature with a high density at the level of the postcapillary venules. Employing specific inhibitors and agonists for two types of histamine receptors, the prevalence of H2 receptors on the venular endothelium was established.
In a variety of nonerythroid cell types, spectrin-like molecules immunologically related to, and sharing biochemical properties with the erythrocyte spectrin have been identified. Spectrin is assumed to function in concert with other cytoscheletal proteins in maintaining the cell shape and restricting the mobility of integral membrane proteins.Employing antibodies against red blood cell spectrin and brain fodrin we demonstrated that endothelial cells express spectrin- and fodrin-like proteins that may play an important role in modulation of the cytoskeleton in response to various stimuli and in maintaining the biochemically differentiated microdomains of plasmalemma.
Transport of plasma hormones and macromolecules through endothelial cells
Transport of thyroid hormones from the blood to target cells is achieved by binding reversibly to albumin which transports and delivers the hormone through the body in a tightly controlled fashion. A double-labeled complex, the radioiodinated thyroxin bound to prealbumin-tagged to 5-nm gold perfused through rat vasculature, accumulates selectively in the lung and heart tissue, by a receptor-mediated process. Electron microscopy autoradiography shows that the hormone is taken up by vesicles (caveolae) of endothelial cells, which participate in its transport across the cell. In time, thyroxin was found in the cell nucleus of neighboring tissue.
Transport of transferrin from the plasma to the tissues takes place by a receptor-dependent process. The cell pathway of transferrin receptors (TfR) was detected in transfected endothelial cells expressing TfR anchored on HRP, as reporter molecule. The newly syntetized TfR-HRP was associated with organelles involved in endocytosis and exocytosis. A remarkable feature was the coexistence within endothelial cells of two subtype of vesicle populations, only one containing TfR-HRP (see figure below).Transport of maternal IgG through the placenta to the fetus is accountable for fetal passive immunity. The role of IgG receptors was investigated in cultured human placental endothelial cells (HPEC). It was found that HPEC (i) bind specifically and internalize IgG via a receptor mediated process; (ii) the binding of IgG occurs through the Fc fragment, with higher efficiency on the basolateral surface; (iii) the cells express neonatal FcR, but not Ig-like FcgRs; (iv) HPEC exhibit on their surface a novel putative FcgR of 55 kDa.
Protein and lipid composition of the membrane microdomains of endothelial cellsEndothelial vesicles (caveolae) are a detergent-resistant microdomain characterized by a specific peptide, caveolin. They function in transcytosis of macromolecules from the plasma to the tissues and have multiple other roles in the physiology of the vascular endothelium. Exposure of endothelial cells to Triton X-100 (in mild conditions) solubilizes the cell membrane whereas the vesicles (individual or in clusters) are detergent-resistant indicating the caveolae as a specific microdomain distinct from the neighboring plasmalemma.
- Vascular Dysfunction in Diabetes and Obesity
- Cerebrovsacular Dysfunction in Ageing and Disease
