The aim of this core is to provide technical support in molecular biology and structural biology to all projects. The structural biology facility has existed in the Division of Hemostasis and Thrombosis for more than a decade with the first paper on the NMR study of a blood coagulation protein published in 1996. Since then, the facility has reported on dozens of structures and key structural elements of coagulation factors. The three components of this core will be 1) NMR spectroscopy, 2) X-ray crystallography, and 3) molecular biology. The NMR spectroscopy component will be managed and operated by Dr. Natalia Beglova, the X-ray crystallography component by Mingdong Huang, and the molecular biology component by Lin Lin. Dr. Beglova is an experienced structural biologist. She combines solution NMR spectroscopy. X-ray crystallography and molecular docking approaches in her research published in peer-reviewed journals including Molecular Cell, Nature Structural Biology, PNAS and Structure. Dr. Huang is a senior X-ray crystallographer. He has solved dozens of protein crystal structure. He has trained 16 PhD students and postdoctoral fellows, and has published more than 60 peer reviewed research articles in journals including Science and Nature. He will be in charge of the administration of Core C and the work related to protein crystallography. Dr. Lin Lin is a senior research associate with extensive experience in both molecular biology, protein expression and structural biology. She has devised a molecular evolution method to optimize enzymatic activity of a lipase. This work shows her expertise in molecular biology. She will be in charge of the work related to protein cloning, expression and crystallization.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HL112302-02
Application #
8532979
Study Section
Special Emphasis Panel (ZHL1-CSR-C)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$186,386
Indirect Cost
$79,267
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Galinski, Christine N; Zwicker, Jeffrey I; Kennedy, Daniel R (2016) Revisiting the mechanistic basis of the French Paradox: Red wine inhibits the activity of protein disulfide isomerase in vitro. Thromb Res 137:169-73
Schulman, Sol; Bendapudi, Pavan; Sharda, Anish et al. (2016) Extracellular Thiol Isomerases and Their Role in Thrombus Formation. Antioxid Redox Signal 24:1-15
Flaumenhaft, Robert; Furie, Bruce (2016) Vascular thiol isomerases. Blood 128:893-901
Bekendam, Roelof H; Bendapudi, Pavan K; Lin, Lin et al. (2016) A substrate-driven allosteric switch that enhances PDI catalytic activity. Nat Commun 7:12579
Lin, Lin; Gopal, Srila; Sharda, Anish et al. (2015) Quercetin-3-rutinoside Inhibits Protein Disulfide Isomerase by Binding to Its b'x Domain. J Biol Chem 290:23543-52
Flaumenhaft, Robert; Furie, Bruce; Zwicker, Jeffrey I (2015) Therapeutic implications of protein disulfide isomerase inhibition in thrombotic disease. Arterioscler Thromb Vasc Biol 35:16-23
Schulman, Sol; Furie, Bruce (2015) How I treat poisoning with vitamin K antagonists. Blood 125:438-42
Passam, Freda H; Lin, Lin; Gopal, Srila et al. (2015) Both platelet- and endothelial cell-derived ERp5 support thrombus formation in a laser-induced mouse model of thrombosis. Blood 125:2276-85
Landeta, Cristina; Blazyk, Jessica L; Hatahet, Feras et al. (2015) Compounds targeting disulfide bond forming enzyme DsbB of Gram-negative bacteria. Nat Chem Biol 11:292-8
Sharda, Anish; Kim, Sarah H; Jasuja, Reema et al. (2015) Defective PDI release from platelets and endothelial cells impairs thrombus formation in Hermansky-Pudlak syndrome. Blood 125:1633-42

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