There are ~23,500 genes in every human cell. While this would appear to be a large number, it is estimated that over 500,000 proteins are present within the cell at any one moment, and furthermore, 80% of these reside in protein heterocomplexes. Many proteins are altered by post-translational modifications that impact subcellullar location, protein activity, protein binding partners and organellar trafficking. All of this complexity impacts gene expression and cell function. Importantly, many protein interactions arise from cell-to-cell- mediated signaling in a tissue-restricted manner and we now understand that protein-protein interactions, signal transduction and gene expression are context-specific. For example, the functional consequences of a given gene expressed during development can be quite different when the same gene is expressed in the adult, as seen with embryonic genes that are re-expressed in cancer cells (1). Indeed, it can be stated with confidence that cell autonomous genetic changes within an incipient cancer cell in collaboration with alterations in the microenvironment contribute to neoplastic progression. The importance of microenvironment and context in neoplastic progression is well accepted (2). Thus, there is increasing need for studies of the genetic and molecular basis of cancer to migrate to the whole organism to correctly capture relevant molecular mechanisms in the proper context. This underlies the rationale for molecular imaging as envisioned by the Washington University In Vivo Cellular and Molecular Imaging Center (WU ICMIC). In particular, integration of genetically encoded imaging reporters into live cells and small animal models of cancer has provided powerful tools to monitor cancer-associated molecular, biochemical, and cellular pathways in vivo (3-6). New animal models combined with imaging techniques (nuclear, MR, fluorescence and bioluminescence) at both macroscopic and microscopic scales will make it possible to explore the consequences of the interactions between tumor cells and microenvironment in vivo in real-time. Ground-breaking studies have demonstrated that molecular imaging is a powerful tool that enables visualization of gene expression, biochemical reactions, signal transduction and regulatory pathways in whole organisms in vivo. Novel injectable agents under development that target key activities may someday enable investigators and clinicians to visualize these processes in patients. With the development of suitable probes and instrumentation for functional imaging in vivo, our ability to identify and measure biological processes in real-time has progressively extended to the whole organism, from mice to humans.
The objective of the WU ICMIC is to combine the institutional expertise of Washington University in the basic sciences of molecular oncology and signal transduction with our well developed infrastructure in medical imaging for the advancement of oncotogic molecular imaging projects. The P50 Program promotes excellence in molecular imaging by providing a regional/national conduit for interdisciplinary collaborations.
|Black, Kvar C L; Akers, Walter J; Sudlow, Gail et al. (2015) Dual-radiolabeled nanoparticle SPECT probes for bioimaging. Nanoscale 7:440-4|
|Kocher, Brandon A; White, Lynn S; Piwnica-Worms, David (2015) DAPK3 suppresses acini morphogenesis and is required for mouse development. Mol Cancer Res 13:358-67|
|Alspach, Elise; Flanagan, Kevin C; Luo, Xianmin et al. (2014) p38MAPK plays a crucial role in stromal-mediated tumorigenesis. Cancer Discov 4:716-29|
|Nickless, Andrew; Jackson, Erin; Marasa, Jayne et al. (2014) Intracellular calcium regulates nonsense-mediated mRNA decay. Nat Med 20:961-6|
|Choi, Jaebok; Cooper, Matthew L; Alahmari, Bader et al. (2014) Pharmacologic blockade of JAK1/JAK2 reduces GvHD and preserves the graft-versus-leukemia effect. PLoS One 9:e109799|
|Garg, Gunjal; Gibbs, Jesse; Belt, Brian et al. (2014) Novel treatment option for MUC16-positive malignancies with the targeted TRAIL-based fusion protein Meso-TR3. BMC Cancer 14:35|
|Hensley, Harvey; Devarajan, Karthik; Johnson, James R et al. (2014) Evaluating new therapies in gastrointestinal stromal tumor using in vivo molecular optical imaging. Cancer Biol Ther 15:911-8|
|Garg, Gunjal; Vangveravong, Suwanna; Zeng, Chenbo et al. (2014) Conjugation to a SMAC mimetic potentiates sigma-2 ligand induced tumor cell death in ovarian cancer. Mol Cancer 13:50|
|Rauch, Daniel A; Harding, John C; Ratner, Lee (2014) IL-15 deficient tax mice reveal a role for IL-1? in tumor immunity. PLoS One 9:e85028|
|Elhammali, Adnan; Ippolito, Joseph E; Collins, Lynne et al. (2014) A high-throughput fluorimetric assay for 2-hydroxyglutarate identifies Zaprinast as a glutaminase inhibitor. Cancer Discov 4:828-39|
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