This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Breast cancer malignancy is characterized by the spreading of cancerous cells into the lymphatic system. Accurate assessment of lymph nodes is a critical component in determining disease progression and subsequent therapeutic options available to patients. Currently, the most common practice of assessing lymph nodes is lymphadecnectomy, a microscopical examination of surgically removed lymph nodes. However, this painful and invasive procedure, which causes nodal destruction and swelling, is not always analytically reliable. Molecular imaging affords non-invasive options for visualizing lymph nodes. However, imaging techniques cannot accurately ascertain the malignancy of the infected lymph nodes, because they display only structures without revealing the bioactivities associated with disease progressions.We seek to develop imaging probes that highlight diseased lymph nodes by detecting a known breast cancer's biological indicator, Cathepsin-B. Cathepsin-B enzymatically cleaves proteins at specific amino acid sequences, and this activity is implicated in the invasion of cancerous cells into they lymph nodes by breaking down the basement membranes. Our proposed molecular probe utilizes Cathepsin-B's native cleaving activity as a specific activation mechanism. The inactive probe is a non-fluorescent compound composed of fluorescent dyes and quenchers attached onto a customized sequence of amino acids. It is activated to the fluorescent species by Cathepsin-B, which selectively cuts off the quenchers. This 'light switch'design reveals specific bioactivity information, which paves the way for non-invasive analytical imaging of lymph nodes.UCSF Mass Spectrometry Facility has the instrumentations and expertise for the characterization of our proposed probes. Mass spectrometry offers efficiency and ease of interpretation that is superior to other spectroscopic tools for our applications.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-BCMB-M (40))
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University of California San Francisco
Schools of Pharmacy
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United States
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Twiss, Jeffery L; Fainzilber, Mike (2016) Neuroproteomics: How Many Angels can be Identified in an Extract from the Head of a Pin? Mol Cell Proteomics 15:341-3
Julien, Olivier; Zhuang, Min; Wiita, Arun P et al. (2016) Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. Proc Natl Acad Sci U S A 113:E2001-10
Cil, Onur; Phuan, Puay-Wah; Lee, Sujin et al. (2016) CFTR activator increases intestinal fluid secretion and normalizes stool output in a mouse model of constipation. Cell Mol Gastroenterol Hepatol 2:317-327
Kintzer, Alexander F; Stroud, Robert M (2016) Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana. Nature 531:258-62
Bongrand, Clotilde; Koch, Eric J; Moriano-Gutierrez, Silvia et al. (2016) A genomic comparison of 13 symbiotic Vibrio fischeri isolates from the perspective of their host source and colonization behavior. ISME J 10:2907-2917
Bikle, Daniel D (2016) Extraskeletal actions of vitamin D. Ann N Y Acad Sci 1376:29-52
Bradshaw, J Michael; McFarland, Jesse M; Paavilainen, Ville O et al. (2015) Prolonged and tunable residence time using reversible covalent kinase inhibitors. Nat Chem Biol 11:525-31
Correia, Maria Almira; Wang, YongQiang; Kim, Sung-Mi et al. (2014) Hepatic cytochrome P450 ubiquitination: conformational phosphodegrons for E2/E3 recognition? IUBMB Life 66:78-88
Wiita, Arun P; Seaman, Julia E; Wells, James A (2014) Global analysis of cellular proteolysis by selective enzymatic labeling of protein N-termini. Methods Enzymol 544:327-58
Tajon, Cheryl A; Seo, Daeha; Asmussen, Jennifer et al. (2014) Sensitive and selective plasmon ruler nanosensors for monitoring the apoptotic drug response in leukemia. ACS Nano 8:9199-208

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