Reverse-phase protein array (RPPA) has emerged as a promising antibody-based highly quantitative proteomic technology suitable for profiling proteins in hundreds to thousands of patient samples. The throughput, sensitivity, and cost effectiveness of RPPA, together with its ability to deal with minuscule sample amounts, have propelled applications of the technology in basic, preclinical and clinical research fields. The technology, which relies heavily on the paucity of high-quality monospecific antibodies, however, is only centered on detecting a few key signaling molecules due to limited availability of high quality phosphospecific antibodies. In this NIH STTR Phase I study, we will develop a novel RPPA platform based on metal ion-functionalized soluble nanopolymers into commercial products for sensitive, high throughput profiling of signaling molecules without the limitation of antibodies. The novel RPPA platform will be applied to distinguish aggressive from indolent human prostate tumors in xenograft mouse models. We hypothesis that prostate cancer can be classified by measuring phosphorylation changes on key oncogenes and thus a RPPA platform can be used as a discovery and preclinical tool to distinguish aggressive from indolent tumors. The following aims will be completed.
Aim #1 : Optimization of functionalized RPPA for capture and detection of phosphopropteins.
Aim #2 : Pathway-activation profiling in indolent and aggressive prostate cancer xenograft mouse models. By the completion of Phase I study, we expect that an analytical platform can be established with high sensitivity, wide dynamic range, excellent reproducibility, and affordable cost.
Protein phosphorylation relates to the onset and development of many cancer types and a highly efficient technology for phosphorylation analysis is critical for cancer research. This NIH STTR Phase I project will support an effort to develop an innovative phosphorylation analysis technology into commercial products that equip researchers with powerful tools and new directions to combat the devastating disease.
| Chen, I-Hsuan; Xue, Liang; Hsu, Chuan-Chih et al. (2017) Phosphoproteins in extracellular vesicles as candidate markers for breast cancer. Proc Natl Acad Sci U S A 114:3175-3180 |
| Pan, Li; Aguilar, Hillary Andaluz; Wang, Linna et al. (2016) Three-Dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation. J Am Chem Soc 138:15311-15314 |
