LaBaer Lab | Research
research: Physical Sciences in Oncology
The NIH initiated a multidisciplinary effort to gain a better understanding of how cancer develops through the Physical Sciences in Oncology (PSOC) program. Scientists in disciplines ranging from medicine to physics will investigate the physical laws of cancer, including cell growth control and response of therapy at protein-protein, cell-cell, and host-tumor levels. There are twelve centers across the United States and the Virginia G. Piper Center for Personalized Diagnostics (CPD) laboratory is part of the PSOC center at the University of Southern California (USC) whose principal investigators include the world-renowned bioinformaticist Dr. Danny Hillis and oncologist Dr. David Agus.
The USC program entitled "Multi-scale Complex Systems Transdisciplinary Analysis of Response to Therapy" (MC-START) is comprised of 4 research programs (Figure 1) that are focused on studying lymphoma as a model cancer system. The CPD laboratory led by Dr. Joshua LaBaer is involved in two of these programs, Research Project 1 (RP1) and Research Project 4 (RP4).
Cell State and Dynamics (Research Project 1 - RP1)
Investigators: D. Mitchell Magee, Ph.D., Brianne Petritis, Steven Means, Manuel Fuentes, Ph.D. and Sanjeeva Srivastava, Ph.D.
Collaborators: Garry Nolan, Ph.D. and Parag Mallick, Ph.D. (Stanford University) and Richard Bonneau, Ph.D. (New York University)
In Research Project 1 (RP1), we are combining the power of NAPPA with surface plasmon resonance imaging (SPRi) to determine the kinetics of protein-protein interactions in various pathways involved in cancer development. The primary objective of RP1 is the development of computational models that reduce the complexity of molecular and cellular events to a small set of inputs (e.g., genetic background of a cell, environmental context) and outputs (e.g., cell physiology, cell state, likelihood of state change). We will combine the studies from multiple laboratories to map the signals within a tumor cell with and without therapeutic treatment. Since our primary cancer model is lymphoma, our initial SPRi studies will focus on B-cell receptor signaling pathway. We will determine the kinetics of protein-protein interactions within the signaling pathway in the presence and absence of therapeutic compounds. Additional studies will include flow cytometry to assess phosphorylation events and studies of various cancer cell lines at multiple treatment stages, which will be performed in Gary Nolan's laboratory. The data from these platforms will be analyzed by Rich Bonneau utilizing a variety of analytical tools including Rosetta. The cumulative efforts will provide analytical methods to model cell signaling pathways involved in tumorigenesis.
Integrated multi-scale analysis of tumor and host response to therapy (Research Project 4 - RP4)
Investigators: D. Mitchell Magee, Ph.D., Brianne Petritis, Steven Means
Collaborators: Shan X. Wang, Ph.D. (Stanford University), Scott Lowe, Ph.D. and Cornelius Miething Ph.D. (Cold Spring Harbor Laboratory), Anand Asthagiri, Ph.D. (Northeastern University), Dan Ruderman,Ph.D. (Applied cpdMinds, Inc), David Agus, Ph.D. (University of Southern California), and Danny Hillis, Ph.D. (Applied Minds, Inc)
Our efforts in RP4 utilize nucleic acid programmable protein arrays (NAPPA) to identify autoantibodies that arise during tumor development. We will first focus on a model lymphoma system and then we will expand these studies to models of lung cancer and acute myelogenous leukemia. In addition to autoantibodies, select cytokines and other proteins will be monitored using a unique magnetonanosensor platform developed by Shan Wang at Stanford University.
Our results from RP1 and RP4 will be analyzed by Anand Asthagiri and Dan Ruderman for patterns of responsiveness to identify key protein pathways involved in the host response to tumor challenge. These results will be fed back to the model developers to assess the effect of these pathways on potential therapeutic interventions. Thus, the integration of the four PSOC research programs will provide fundamental new modalities to predict response to therapy.