The overall goals ofthe Development Fund Program are to 1) provide seed funding for novel, creative and early, high risk research projects, 2) promote interdisciplinary research projects and 3) recruit new investigators into the field of cancer molecular imaging. This funding mechanism has had a significant impact on the discovery of important aspects of tumor biology through a) the use of in vivo imaging, b) the development of novel technologies and agents, and c) the advancement of research tools from bench to bedside and back. In the past, this type of funding mechanism has led to significant discoveries within our Center, including the creation of enzyme-activatable imaging probes and magnetic cell trackers or fusion proteins to image gene expression. Two specific Developmental Fund projects were identified for the first year of funding. The first project (""""""""New candidate molecular imaging targets for pancreatic ductal adenocarcinoma from functional genomics"""""""") identified cathepsin E (CTSE) as a novel PDAC-specific imaging target based on large scale genomic profiling.
The specific aims are to 1) synthesize and characterize a cell permeable affinity based probe for CTSE and then perform proof-of-principle studies (histochemistry, cell based imaging) and 2) to validate the imaging probe in the Kras/p53 genetically engineered mouse model of PDAC. The second project (""""""""Intraoperative single cell imaging of sarcoma resection"""""""") applies recent advances in intraoperative imaging systems and probes to the resection of soft tissue sarcoma. The PI hypothesize that the use of multiple markers, visualized at cellular resolution, will provide more complete information during surgery, not only by conveying the location of neoplastic cells, but also by informing on the infiltration or encapsulation status ofthe border regions.
The specific aims are to 1) synthesize and test imaging probes (EGFR-targeted, host probes and neovasculature) in a mouse model of sarcoma and 2) develop a mathematical framework for describing theoretical pharmacokinetics to address constraints such as probe type, administration route, and imaging performance as a function of biomarker expression. Additional applications will be solicited in subsequent years and peer reviewed by the Internal Steering Committee. Priority will be given to proposals which 1) are interdisciplinary and involve a synthesis of molecular/cellular and imaging sciences, 2) make synergistic use ofthe Specialized Resources and 3) employ highly innovative concepts
|Pfirschke, Christina; Engblom, Camilla; Rickelt, Steffen et al. (2016) Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy. Immunity 44:343-54|
|Ghosh, Balaram; Zhao, Wen-Ning; Reis, Surya A et al. (2016) Dissecting structure-activity-relationships of crebinostat: Brain penetrant HDAC inhibitors for neuroepigenetic regulation. Bioorg Med Chem Lett 26:1265-71|
|Roy, Jeremy; Kim, Bongki; Hill, Eric et al. (2016) Tyrosine kinase-mediated axial motility of basal cells revealed by intravital imaging. Nat Commun 7:10666|
|Wu, Juwell W; Turcotte, RaphaÃ«l; Alt, Clemens et al. (2016) Defining Clonal Color in Fluorescent Multi-Clonal Tracking. Sci Rep 6:24303|
|Reis, Surya A; Ghosh, Balaram; Hendricks, J Adam et al. (2016) Light-controlled modulation of gene expression by chemical optoepigenetic probes. Nat Chem Biol 12:317-23|
|Pucci, Ferdinando; Rickelt, Steffen; Newton, Andita P et al. (2016) PF4 Promotes Platelet Production and Lung Cancer Growth. Cell Rep 17:1764-1772|
|Miller, Miles A; Weissleder, Ralph (2016) Imaging the pharmacology of nanomaterials by intravital microscopy: Toward understanding their biological behavior. Adv Drug Deliv Rev :|
|Vinegoni, Claudio; Dubach, John M; Feruglio, Paolo Fumene et al. (2016) Two-photon Fluorescence Anisotropy Microscopy for Imaging and Direct Measurement of Intracellular Drug Target Engagement. IEEE J Sel Top Quantum Electron 22:|
|Meimetis, Labros G; Boros, Eszter; Carlson, Jonathan C et al. (2016) Bioorthogonal Fluorophore Linked DFO-Technology Enabling Facile Chelator Quantification and Multimodal Imaging of Antibodies. Bioconjug Chem 27:257-63|
|Pucci, Ferdinando; Garris, Christopher; Lai, Charles P et al. (2016) SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science 352:242-6|
Showing the most recent 10 out of 309 publications