Molecular heterogeneity is central to the development of therapeutic resistance in cancer patients. Current pathology practices are not sufficient for analyzing the molecular and functional properties of heterogeneous populations within a tumor. New approaches are needed for obtaining and using this information to guide more effective treatments that anticipate and suppress therapeutic resistance, and that improve the outcome for patients with cancer. Project 4 develops platforms combining nano-, chemical and micro-technologies with biological content to facilitate highly multiplexed quantitative molecular and functional measurements of small tumor samples directiy from the operafing room. The technology mix allows us to perform highly multiplexed biological measurements on small enough samples so that we can effectively address the questions of heterogeneity within solid glioblastoma tumors. The glioblastoma focus of this project permits leveraging the expertise of the investigators and established infrastructure developed during years 1-4 of our CCNE. This infrastructure includes access to meticulously characterized clinical samples, powerful mouse models, and companion grants obtained over the past few years that pave the way for integration of these technologies into the clinic. The technology pathway within this project begins by leveraging off of the platform of DNA encoded anfibody libraries (DEAL) that was developed under current CCNE funding. We extend this platform to a host of new measurement types for analyzing tumor molecular heterogeneity resolved to the single cell level. The biological content makes these platforms clinically relevant and adds significant value for commercialization.
We aim to develop technologies and approaches that provide information relevant to the clinical care of GBM pafients, but which should also be broadly applicable to other solid tumor cancers. We have assembled highly cross-disciplinary, interactive team that has several years of experience at working together. Our team bridges from the physical science lab to the oncology clinic.

Public Health Relevance

This project develops powerful new in vitro diagnostic platforms for quantitative molecular analysis of small heterogeneous tumor samples directly from the operating room. The biological content makes these platforms clinically relevant.and adds significant value for commercialization. The tools and knowledge developed in this project will be broadly applicable to guiding more effective therapy for patients with cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
California Institute of Technology
United States
Zip Code
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 14:1590-601
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
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
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
Ghosh, Dhiman; Ulasov, Ilya V; Chen, LiPing et al. (2016) TGFβ-Responsive HMOX1 Expression Is Associated with Stemness and Invasion in Glioblastoma Multiforme. Stem Cells 34:2276-89
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 29:563-73
Shin, Daniel Sanghoon; Ribas, Antoni (2015) The evolution of checkpoint blockade as a cancer therapy: what's here, what's next? Curr Opin Immunol 33:23-35
Pan, Dorothy W; Davis, Mark E (2015) Cationic Mucic Acid Polymer-Based siRNA Delivery Systems. Bioconjug Chem 26:1791-803
Xue, Min; Wei, Wei; Su, Yapeng et al. (2015) Chemical methods for the simultaneous quantitation of metabolites and proteins from single cells. J Am Chem Soc 137:4066-9
Tanaka, Kazuhiro; Sasayama, Takashi; Irino, Yasuhiro et al. (2015) Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment. J Clin Invest 125:1591-602

Showing the most recent 10 out of 50 publications