A5052288239- TGF-β signaling in diseases
- Bone Metabolism and Diseases
- Bone health and treatments
- Muscle Physiology and Disorders
- Porphyrin Metabolism and Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Pulmonary Hypertension Research and Treatments
- Parathyroid Disorders and Treatments
- Acute Myeloid Leukemia Research
- Iron Metabolism and Disorders
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Multiple Myeloma Research and Treatments
- Adipose Tissue and Metabolism
- Erythropoietin and Anemia Treatment
- Metabolism, Diabetes, and Cancer
- Porphyrin and Phthalocyanine Chemistry
- Genetic factors in colorectal cancer
- Endoplasmic Reticulum Stress and Disease
- Heterotopic Ossification and Related Conditions
- Protein Kinase Regulation and GTPase Signaling
- Cardiomyopathy and Myosin Studies
- T-cell and B-cell Immunology
- GDF15 and Related Biomarkers
Acceleron Pharma (United States)
2007-2023
RWTH Aachen University
2012
Harvard University
2012
Massachusetts General Hospital
2012
Universitätsklinikum Aachen
2012
Reproductive Genetics Institute
1985
Boston University
1985
Massachusetts Institute of Technology
1984
University of Southampton
1979-1983
The present study shows that recombinant interleukin 2 (IL-2) purified to homogeneity induces a rapid and potent enhancement of spontaneous cytotoxicity human peripheral blood lymphocytes. cells mediating after 18-h treatment with IL-2 have surface markers natural killer (NK) are generated from the subset containing cytotoxic cells. A parallel production gamma interferon (IFN-gamma) is induced by (rIL-2), NK appear be major producer cells, whereas T unable produce IFN-gamma under these...
ABSTRACT Patients with chronic inflammation are burdened anemia of (AI), where inflammatory cytokines inhibit erythropoiesis, impede erythropoietin production, and limit iron availability by inducing the regulator hepcidin. High hepcidin hinders absorption recycling, thereby worsening impaired erythropoiesis restricting availability. AI management is important as impacts quality life potentially affects morbidity mortality. The bone morphogenetic protein (BMP)‐SMAD pathway crucial for...
Interleukin-3 (IL-3) is a member of family growth factors, each which supports the proliferation and development hematopoietic precursors in culture. Although biologic effects different factors have been well documented culture systems, it has only recently become possible to study activities these molecules vivo. In comparison with later acting granulocyte-macrophage colony-stimulating factor (GM-CSF) granulocyte factor, IL-3 elicited delayed relatively modest leukocytosis when continuously...
We report the purification, molecular cloning, and expression of a novel cytosolic calcium-independent phospholipase A2 (iPLA2) from Chinese hamster ovary cells, which lacks extended homology to other phospholipases. iPLA2 is an 85-kDa protein that exists as multimeric complex 270-350 kDa with specific activity 1 μmol/min/mg. The full-length cDNA clone encodes 752-amino acid cytoplasmic one lipase motif (GXS465XG) eight ankyrin repeats. Expression in mammalian cells generates active protein....
Understanding the pathogenesis of cancer-related bone disease is crucial to discovery new therapies. Here we identify activin A, a TGF-β family member, as therapeutically amenable target exploited by multiple myeloma (MM) alter its microenvironmental niche favoring osteolysis. Increased marrow plasma A levels were found in MM patients with osteolytic disease. cell engagement stromal cells enhanced secretion via adhesion-mediated JNK activation. Activin turn, inhibited osteoblast...
Endoglin (CD105), a transmembrane protein of the transforming growth factor β superfamily, plays crucial role in angiogenesis. Mutations endoglin result vascular defect known as hereditary hemorrhagic telangiectasia (HHT1). The soluble form was suggested to contribute pathogenesis preeclampsia. To obtain further insight into its function, we cloned, expressed, purified, and characterized extracellular domain (ECD) mouse human fused an immunoglobulin Fc domain. We found that ECD-Fc bound...
The effects of ACE-011 on safety, pharmacokinetics, and bone biomarkers were evaluated in healthy, postmenopausal women. Our data indicate that results a sustained increase formation reduction markers resorption. activin type IIA receptor (ActRIIA) is the high-affinity for activin. dimeric fusion protein consisting extracellular domain human ActRIIA linked to Fc portion IgG1. binds activin, preventing from binding endogenous receptors. A randomized, double-blind, placebo-controlled study was...
The expression of bone morphogenetic proteins (BMPs) is enhanced in human atherosclerotic and calcific vascular lesions. Although genetic gain- loss-of-function experiments mice have supported a causal role BMP signaling atherosclerosis calcification, it remains uncertain whether might be targeted pharmacologically to ameliorate both these processes.We tested the impact pharmacological inhibition on calcification LDL receptor-deficient (LDLR-/-) mice. LDLR-/- fed high-fat diet developed...
Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members TGF-beta superfamily have been shown be involved in mass. Activin A, a signaling ligand, is present at high levels may play role metabolism. Here we demonstrate pharmacological blockade ligand through affinity receptor for activin, type II activin (ActRIIA), by administration soluble extracellular domain ActRIIA fused murine IgG2a-Fc, increases formation, mass, strength...
Members of the transforming growth factor β (TGF-β) family have been genetically linked to vascular formation during embryogenesis. However, contradictory studies about role TGF-β and other members with reported functions, such as bone morphogenetic protein (BMP) 9, in physiological pathological angiogenesis make need for mechanistic apparent. We demonstrate, by genetic pharmacological means, that BMP9 receptor activin receptor-like kinase (ALK) 1 represents a new therapeutic target tumor...
Abstract Activin receptor–like kinase-1 (ALK1) is a type I, endothelial cell–specific member of the transforming growth factor-β superfamily receptors known to play an essential role in modulating angiogenesis and vessel maintenance. In present study, we sought examine angiogenic tumorigenic effects mediated upon inhibition ALK1 signaling using soluble chimeric protein (ALK1-Fc). Of 29 factor-β–related ligands screened by surface plasmon resonance, only bone morphogenetic (BMP9) BMP10...
The single transmembrane domain serine/threonine kinase activin receptor type IIB (ActRIIB) has been proposed to bind key regulators of skeletal muscle mass development, including the ligands GDF-8 (myostatin) and GDF-11 (BMP-11). Here we provide a detailed kinetic characterization ActRIIB binding several low high affinity using soluble IIB-Fc chimera (ActRIIB.Fc). We show that both extracellular with affinities comparable those A, known ligand, whereas BMP-2 BMP-7 for are at least 100-fold...
Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack remodeling by stimulating osteoclastic resorption suppressing formation. Currently, treatment is targeted primarily at blocking resorption, but this approach has achieved only limited success. Stimulating osteoblastic formation to promote repair a novel alternative approach. We show soluble activin receptor type IIA fusion protein (ActRIIA.muFc)...
Direct interaction between platelet receptor glycoprotein Ibalpha (GpIbalpha) and thrombin is required for aggregation activation at sites of vascular injury. Abnormal GpIbalpha-thrombin binding associated with many pathological conditions,including occlusive arterial thrombosis bleeding disorders. The crystal structure the complex 2.6 angstrom resolution reveals simultaneous interactions GpIbalpha exosite I one molecule,and II a second molecule. In lattice,the periodic arrangement complexes...
Obesity results from disproportionately high energy intake relative to expenditure. Many therapeutic strategies have focused on the side of equation, including pharmaceutical targeting appetite and digestion. An alternative approach is increase expenditure through physical activity or adaptive thermogenesis. A pharmacological way muscle mass hence exercise capacity inhibition activin receptor type IIB (ActRIIB). Muscle strength regulated, at least in part, by growth factors that signal via...