The overall goal of this UOI application is to create and support a highly multidisciplinary team of chemists, biologists, engineers and physicians to develop and rapidly translate new nanotechnologies to better diagnose and treat heart, lung, blood and sleep (HLBS) disorders. The current team includes investigators from the newly formed Broad Institute, Massachusetts Institute of Technology (MIT), Harvard Faculty of Arts and Sciences (FAS), Harvard Medical School (HMS), Massachusetts General Hospital (MGH) and Brigham and Women's Hospital (BWH). Specific applications of nanotechnology in this application include noninvasive imaging and sensing, targeted therapies, tissue repair and regeneration and drug delivery. The team's aims are to: 1. (Stellacci, Josephson) investigate novel metal and semiconductor nanoparticles for improved in vivo sensing and targeting. 2. (Shaw, Perez, Weissleder, Schreiber) create and test entire libraries of nanoparticles as a proof-of-principle to rapidly engineer nanomaterials with precise biological function. 3. (Shaw, Schreiber) develop multidimensional cell screens to rapidly and sensitively test biosafety of novel materials. 4. (Lee, Zhang, Anversa) harness smart scaffolds capable of growth factor release to promote cardiovascular tissue regeneration (""""""""liquid heart""""""""). 5. (Libby, Weissleder, Swager) utilize novel polymeric composites to sense reactive oxygen species in vulnerable plaque. 6. (Shapiro, Tung) utilize novel protease sensors for early in vivo sensing of smoke induced lung injury. 7. (Jaffer, Reed, Wagner) test novel targeted and activatable fibrinolytic scaffolds for enhanced therapies of thrombotic events. It is anticipated that these advances in nanotechnology will significantly advance medical science and treatment of HLBS disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL080731-03
Application #
7221966
Study Section
Special Emphasis Panel (ZHL1-CSR-K (F1))
Program Officer
Buxton, Denis B
Project Start
2005-07-01
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$3,302,454
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Libby, Peter; King, Kevin (2015) Biomarkers: A Challenging Conundrum in Cardiovascular Disease. Arterioscler Thromb Vasc Biol 35:2491-5
Konishi, Masanori; Erdem, S Sibel; Weissleder, Ralph et al. (2015) Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis. Circ Res 117:502-512
Kessinger, Chase W; Kim, Jin Won; Henke, Peter K et al. (2015) Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring. PLoS One 10:e0116621
Gaglia, Jason L; Harisinghani, Mukesh; Aganj, Iman et al. (2015) Noninvasive mapping of pancreatic inflammation in recent-onset type-1 diabetes patients. Proc Natl Acad Sci U S A 112:2139-44
Libby, Peter; Hansson, Göran K (2015) Inflammation and immunity in diseases of the arterial tree: players and layers. Circ Res 116:307-11
Libby, Peter; Tabas, Ira; Fredman, Gabrielle et al. (2014) Inflammation and its resolution as determinants of acute coronary syndromes. Circ Res 114:1867-79
Libby, Peter; Lichtman, Andrew H; Hansson, Göran K (2013) Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity 38:1092-104
Shao, Huilin; Min, Changwook; Issadore, David et al. (2012) Magnetic Nanoparticles and microNMR for Diagnostic Applications. Theranostics 2:55-65
Issadore, David; Chung, Jaehoon; Shao, Huilin et al. (2012) Ultrasensitive clinical enumeration of rare cells ex vivo using a micro-hall detector. Sci Transl Med 4:141ra92
Min, Changwook; Shao, Huilin; Liong, Monty et al. (2012) Mechanism of magnetic relaxation switching sensing. ACS Nano 6:6821-8

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