Proteolysis is of paramount importance to biological regulation, and its significance is magnified because it is irreversible. Proteolysis regulates the four fundamental aspects of cell behavior; division, death, differentiation and motility. Proteolytic pathways are key to the pathology of virtually every type of human disease including, infection, inflammation, thrombosis, cancer, emphysema, Alzheimer's, etc. The importance and impact of understanding proteolysis 'in total' will be immense. Achieving this ultimate goal will be a considerable challenge, and one that will require an ambitious and coordinated effort. Here we propose to form the Center on Proteolytic Pathways (CPP), a National Resource for the study of proteases, their inhibitors, their products, and upstream and downstream regulatory pathways. The strategic goal of the CPP is to develop The Protease Pathway Interrogation Platform (PPIP) technology. This platform technology will be comprised of four foundation technologies; (1) Activity-based Protease Profiling, (2) Protease Activity Imaging Technology, (3) Product Terminal Isotope Coding, and (4) the in silico environment called Protease Map. A key and unique feature of this technology platform is its focus squarely on measuring activity, as opposed to just abundance. The CPP will contain a Training component to ensure that a new cadre of scientists is trained to tackle protease biology with the most modem of techniques and most cutting edge technology. An Outreach component is planned to ensure that the CPP achieves high visibility, and ultimately numerous connections, with the scientific research community.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54RR020843-05S1
Application #
7683406
Study Section
Special Emphasis Panel (ZRG1-BST-D (55))
Program Officer
Sheeley, Douglas
Project Start
2004-09-30
Project End
2010-07-31
Budget Start
2008-08-01
Budget End
2010-07-31
Support Year
5
Fiscal Year
2008
Total Cost
$269,998
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Savinov, Alexei Y; Strongin, Alex Y (2013) Targeting the T-cell membrane type-1 matrix metalloproteinase-CD44 axis in a transferred type 1 diabetes model in NOD mice. Exp Ther Med 5:438-442
Moin, Kamiar; Sameni, Mansoureh; Victor, Bernadette C et al. (2012) 3D/4D functional imaging of tumor-associated proteolysis: impact of microenvironment. Methods Enzymol 506:175-94
Mueller, Kelly L; Madden, Julie M; Zoratti, Gina L et al. (2012) Fibroblast-secreted hepatocyte growth factor mediates epidermal growth factor receptor tyrosine kinase inhibitor resistance in triple-negative breast cancers through paracrine activation of Met. Breast Cancer Res 14:R104
Giordano, Courtney R; Mueller, Kelly L; Terlecky, Laura J et al. (2012) A targeted enzyme approach to sensitization of tyrosine kinase inhibitor-resistant breast cancer cells. Exp Cell Res 318:2014-21
Bush, Jason A; Kitaura, Hideki; Ma, Yuliang et al. (2012) Comparative proteomic analysis of a cytosolic fraction from ?3 integrin-deficient cells. Cancer Genomics Proteomics 9:1-13
Mullins, Stefanie R; Sameni, Mansoureth; Blum, Galia et al. (2012) Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins. Biol Chem 393:1405-16
Békés, Miklós; Prudden, John; Srikumar, Tharan et al. (2011) The dynamics and mechanism of SUMO chain deconjugation by SUMO-specific proteases. J Biol Chem 286:10238-47
Ren, Gang; Blum, Galia; Verdoes, Martijn et al. (2011) Non-invasive imaging of cysteine cathepsin activity in solid tumors using a 64Cu-labeled activity-based probe. PLoS One 6:e28029
Irwin, Mary E; Bohin, Natacha; Boerner, Julie L (2011) Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells. Cancer Biol Ther 12:718-26
Zhu, Wenhong; Fang, Changming; Gramatikoff, Kosi et al. (2011) Proteins and an inflammatory network expressed in colon tumors. J Proteome Res 10:2129-39

Showing the most recent 10 out of 140 publications