A5050570036- Ion Channels and Receptors
- Nitric Oxide and Endothelin Effects
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Neurobiology and Insect Physiology Research
- Pulmonary Hypertension Research and Treatments
- Glycosylation and Glycoproteins Research
- Renal Diseases and Glomerulopathies
- PI3K/AKT/mTOR signaling in cancer
- Ion channel regulation and function
- Inflammasome and immune disorders
- Caveolin-1 and cellular processes
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Phytochemicals and Antioxidant Activities
- RNA modifications and cancer
- Retinoids in leukemia and cellular processes
- Cellular Mechanics and Interactions
- Neuroscience of respiration and sleep
- RNA Interference and Gene Delivery
- Cardiac electrophysiology and arrhythmias
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Biochemical Analysis and Sensing Techniques
- MicroRNA in disease regulation
- Regulation of Appetite and Obesity
- Renin-Angiotensin System Studies
Leipzig University
2016-2025
Research Institute of Human Morphology
2023
National Medical Research Center of Cardiology
2023
Institute of Experimental Cardiology
2023
Institute for Atherosclerosis Research
2023
Research Institute of General Pathology and Pathophysiology, the Russian Academy of Medical Sciences
2023
Brigham and Women's Hospital
2010-2017
Harvard University
2010-2017
Cardiovascular Research Center
2014
Harvard Stem Cell Institute
2013
Among the TRPC subfamily of TRP (classical transient receptor potential) channels, TRPC3, -6, and -7 are gated by signal transduction pathways that activate C-type phospholipases as well direct exposure to diacylglycerols. Since TRPC6 is highly expressed in pulmonary vascular smooth muscle cells, it represents a likely molecular candidate for receptor-operated cation entry. To define physiological role TRPC6, we have developed TRPC6-deficient mouse model. These mice showed an elevated blood...
In 2017, four independent publications described the glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as for growth differentiation 15 (GDF15, also MIC-1, NAG-1) with an expression exclusively in mice brainstem area postrema (AP) and nucleus tractus solitarii (NTS) where it mediates effects of GDF15 on reduction food intake body weight. is a cell stress cytokine widespread pleiotropic effects, which both seem to be contrast reported highly specialized localization...
Regional alveolar hypoxia causes local vasoconstriction in the lung, shifting blood flow from hypoxic to normoxic areas, thereby maintaining gas exchange. This mechanism is known as pulmonary (HPV). Disturbances HPV can cause life-threatening hypoxemia whereas chronic triggers lung vascular remodeling and hypertension. The signaling cascade of this vitally important still unresolved. Using transient receptor potential channel 6 (TRPC6)-deficient mice, we show that a key regulator acute...
The TRPC family of receptor-activated cation channels (TRPC channels) can be subdivided into four subfamilies based on sequence homology as well functional similarities. Members the TRPC3/6/7 subfamily share common biophysical characteristics and are activated by diacylglycerol in a membrane-delimited manner. At present, it is only poorly understood whether members functionally redundant or they serve distinct cellular roles. By electrophysiological fluorescence imaging strategies we show...
Lung ischaemia-reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary induced by endothelial dysfunction. Here we show lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2(y/-)) or the classical transient receptor potential channel 6 (TRPC6(-/-)) are protected LIR-induced (LIRE). Generation of chimeric bone marrow cell transplantation and endothelial-specific Nox2 deletion showed Nox2, but not leukocytic TRPC6, responsible...
Caveolin-1 is a scaffolding/regulatory protein that interacts with diverse signaling molecules. Caveolin-1null mice have marked metabolic abnormalities, yet the underlying molecular mechanisms are incompletely understood. We found redox stress plasma biomarker 8-isoprostane was elevated in caveolin-1null mice, and discovered siRNA-mediated caveolin-1 knockdown endothelial cells promoted significant increases intracellular H2O2. Mitochondrial ROS production increased after knockdown;...
Non-selective cation influx through canonical transient receptor potential channels (TRPCs) is thought to be an important event leading airway inflammation. TRPC6 highly expressed in the lung, but its role allergic processes still poorly understood.The purpose of this study was evaluate hyperresponsiveness (AHR) and inflammation lung.Methacholine-induced AHR assessed by head-out body plethysmography wild type (WT) TRPC6(-/-) mice. Experimental induced intraperitoneal ovalbumin (OVA)...
Nitric oxide (NO) and hydrogen peroxide (H 2 O ) are synthesized within cardiac myocytes play key roles in modulating cardiovascular signaling. Cardiac contain both the endothelial (eNOS) neuronal (nNOS) NO synthases, but differential of these NOS isoforms interplay reactive oxygen species nitrogen signaling pathways poorly understood. Using a recently developed chemical sensor [Cu (FL2E)] to study adult from wild-type, eNOS null , nNOS mice, we discovered that physiological concentrations H...
Abstract Glia play critical roles in maintaining the structure and function of nervous system; however, specific contribution that astroglia make to neurodegeneration human disease states remains largely undefined. Here we use Alexander disease, a serious degenerative neurological disorder caused by astrocyte dysfunction, identify glial-derived NO as signalling molecule triggering astrocyte-mediated neuronal degeneration. We further find acts through cGMP neurons promote cell death. Glial...
The MARCKS protein (myristoylated alanine-rich C kinase substrate) is an actin- and calmodulin-binding that expressed in many mammalian tissues. role of endothelial signaling responses incompletely understood. We found siRNA-mediated knockdown cultured cells abrogated directed cell movement a wound healing assay. used biochemical imaging approaches to explore the signal transduction pathways activated by insulin. Insulin treatment vascular promoted dose- time-dependent phosphorylation...
The adhesion G protein–coupled receptor (aGPCR) GPR126/ADGRG6 plays an important role in several physiological functions, such as myelination or peripheral nerve repair. This renders the attractive pharmacological target. GPR126 is a mechano-sensor that translates binding of extracellular matrix (ECM) molecules to its N terminus into metabotropic intracellular signal. To date, structural requirements and character forces needed for this ECM-mediated activation are largely unknown. In study,...
Abstract Purpose: In small cell lung cancer cells (SCLC), various autocrine stimuli lead to the parallel activation of Gq/11 and G12/13 proteins. Although contribution Gq/11-phospholipase C-β cascade mitogenic effects in SCLC is well established, relevance signaling still elusive. other tumor entities, promotes invasiveness without affecting cellular proliferation. Here, we investigate role G12/13-dependent SCLC. Experimental Design: We used hairpin RNA–mediated targeting Gα12, Gα13, or both...