The objectives of Core B are to provide Imaging services, antibodies, and antibody production services to the individual components of the Program Project. At the request of the other Pis, Dr. Sakai will discuss experiments, devise appropriate experimental strategies and protocols, and then perform agreed upon services. Imaging Services: Transmission electron microscopy (including immunolocalization as well as standard ultrastructural imaging) and confocal microscopy are available to all of the Projects. Antibodies: The following well-characterized antibodies will be distributed to the Projects upon request: rabbit polyclonal antibodies specific for fibrillin-1, fibrillin-2, LTBP-1, and LTBP-4;monoclonal antibodies specific for fibrillin and for BMP-7. These antibodies are all suitable for use with mouse materials. In addition, the Core can provide monoclonal antibodies specific for flbrillin-1, fibrillin-2, and fibrillin-3, and for elastin, which react with human, bovine, and avian fibrillins. The Core has also produced and characterized monoclonal antibodies specific for human fibulin-4. Custom-made antibodies: Rabbit polyclonal or mouse monoclonal antibodies can be generated, in consultation with Project Pis. Project Pis will provide the immunogen and will also perform some assistance with antibody screening and characterization. Because commercial sources of pSmad 2/3 antibodies have been unreliable and inconsistent, we will synthesize phospho-Smad peptides to use as immunogens, generate and characterize our own reliable pSmad2/3 antibodies. Recombinant proteins: Limited supplies of recombinant proteins are also available. These include recombinant fibrillin-1 and fibrillin-2 polypeptides;recombinant LTBP-1, LTBP-2, LTBP-3 and LTBP-4 polypeptides;and recombinant BMP-7.

Public Health Relevance

Core B supports the goals of the Program Project by providing specialized imaging expertise and instrumentation, as well as experience in interpretation of connective tissue structure, that is available in only a few places in the world. In addition, the collection of antibody reagents and immunochemical expertise relevant to the goals ofthe Program Project is outstanding. All Projects benefit from the services available.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR049698-10
Application #
8527716
Study Section
Special Emphasis Panel (ZAR1-MLB-F)
Project Start
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
10
Fiscal Year
2013
Total Cost
$35,645
Indirect Cost
$30,818
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Walji, Tezin A; Turecamo, Sarah E; DeMarsilis, Antea J et al. (2016) Characterization of metabolic health in mouse models of fibrillin-1 perturbation. Matrix Biol 55:63-76
Bellini, C; Korneva, A; Zilberberg, L et al. (2016) Differential ascending and descending aortic mechanics parallel aneurysmal propensity in a mouse model of Marfan syndrome. J Biomech 49:2383-9
Smaldone, Silvia; Ramirez, Francesco (2016) Fibrillin microfibrils in bone physiology. Matrix Biol 52-54:191-7
Horiguchi, Masahito; Todorovic, Vesna; Hadjiolova, Krassimira et al. (2015) Abrogation of both short and long forms of latent transforming growth factor-β binding protein-1 causes defective cardiovascular development and is perinatally lethal. Matrix Biol 43:61-70
Dabovic, Branka; Robertson, Ian B; Zilberberg, Lior et al. (2015) Function of latent TGFβ binding protein 4 and fibulin 5 in elastogenesis and lung development. J Cell Physiol 230:226-36
Cook, J R; Carta, L; Galatioto, J et al. (2015) Cardiovascular manifestations in Marfan syndrome and related diseases; multiple genes causing similar phenotypes. Clin Genet 87:11-20
Cook, Jason R; Clayton, Nicholas P; Carta, Luca et al. (2015) Dimorphic effects of transforming growth factor-β signaling during aortic aneurysm progression in mice suggest a combinatorial therapy for Marfan syndrome. Arterioscler Thromb Vasc Biol 35:911-7
Sengle, Gerhard; Sakai, Lynn Y (2015) The fibrillin microfibril scaffold: A niche for growth factors and mechanosensation? Matrix Biol 47:3-12
Doyle, Jefferson J; Doyle, Alexander J; Wilson, Nicole K et al. (2015) A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome. Elife 4:
Robertson, Ian B; Horiguchi, Masahito; Zilberberg, Lior et al. (2015) Latent TGF-β-binding proteins. Matrix Biol 47:44-53

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