Organ-specific, blood protein biomarkers for an informative diagnosis of brain and ovarian cancers: technologies for rapid evaluation, validation, and clinical translation Abstract. Our first hypothesis is that organ-specific, secreted biomarkers constitute a molecular fingerprint of the biological networks in each organ. These proteins can change during the progression from health to disease and disease treatment, and provide information relevant to early diagnosis, disease stratification and progression, and therapy response. These markers provide an exciting opportunity for brain and ovarian cancer diagnostics. Our second hypothesis is that highly multiplexed measurements of serum-based protein biomarkers will become a routine clinical tool only if those measurements are quantitative, highly sensitive, and inexpensive. These two hypotheses drive the biology and technology within this project. We describe a blood protein biomarker discovery and validation pathway, as applied to qlioblastoma multiforme (GBM) and ovarian cancer. The pathway begins with the identification of potential organ-specific blood proteins via comparative deep transcriptome analysis, coupled with a search of extant blood protein databases. These biomarkers are pre-validated using unique mass spectrometric methods applied to mouse models and human sera. The most promising markers are translated onto a chip for large scale validation on cancer patients via analysis of a pinprick of blood. The fourth step is to replace the most expensive aspect of those measurements (the antibodies) with a more stable but equal performance alternative. Two nanotechnologies enable this approach. They are protein click-catalyzed capture agents (PCC agents), which are highly modular, chemically synthesized protein capture agents that are assembled by the protein target itself. PCC agents can exhibit the affinity and selectivity of antibodies, but also (bio)chemical and physical stability - thus permitting the routine use of highly multiplexed protein assays. The second nanotechnology permits the routine counting of individual, specific protein molecules, thus extending the sensitivity of multiplexed protein assays by orders of magnitude (and thus to small organs).
Technologies for identifying biomarkers relevant to the early diagnosis, disease stratification, and therapy response for ovarian cancer patients and glioblastoma cancer patients are described. Those technologies are designed to increase the accuracy and specificity of current diagnostic approaches, at reduced cost.
|Su, Yapeng; Shi, Qihui; Wei, Wei (2017) Single cell proteomics in biomedicine: High-dimensional data acquisition, visualization, and analysis. Proteomics 17:|
|Collins, Jeffrey; Waldmann, Christopher M; Drake, Christopher et al. (2017) Production of diverse PET probes with limited resources: 24 18F-labeled compounds prepared with a single radiosynthesizer. Proc Natl Acad Sci U S A 114:11309-11314|
|Turner, Kristen M; Deshpande, Viraj; Beyter, Doruk et al. (2017) Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature 543:122-125|
|Ghosh, Dhimankrishna; Funk, Cory C; Caballero, Juan et al. (2017) A Cell-Surface Membrane Protein Signature for Glioblastoma. Cell Syst 4:516-529.e7|
|Hong, Candice Sun; Graham, Nicholas A; Gu, Wen et al. (2016) MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4. Cell Rep 14:1590-1601|
|Henning, Ryan K; Varghese, Joseph O; Das, Samir et al. (2016) Degradation of Akt using protein-catalyzed capture agents. J Pept Sci 22:196-200|
|Wei, Wei; Shin, Young Shik; Xue, Min et al. (2016) Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma. Cancer Cell 29:563-573|
|Poovathingal, Suresh Kumar; Kravchenko-Balasha, Nataly; Shin, Young Shik et al. (2016) Critical Points in Tumorigenesis: A Carcinogen-Initiated Phase Transition Analyzed via Single-Cell Proteomics. Small 12:1425-31|
|Ghosh, Dhiman; Ulasov, Ilya V; Chen, LiPing et al. (2016) TGF?-Responsive HMOX1 Expression Is Associated with Stemness and Invasion in Glioblastoma Multiforme. Stem Cells 34:2276-89|
|Clark, Andrew J; Wiley, Devin T; Zuckerman, Jonathan E et al. (2016) CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing. Proc Natl Acad Sci U S A 113:3850-4|
Showing the most recent 10 out of 54 publications