OCSSB is the home or a partner to many innovative research projects which have been awarded funding from both federal agencies and private foundations. The current major funded research projects at OCSSB are described below, as well as some of our other ongoing research work.
Major funded research projects
Mapping human cancers
NCI Human Tumor Atlas Network (HTAN) research center - Omic and Multidimensional Spatial (OMS) Atlas
Lead Investigators: Joe Gray, Gordon Mills, Jeremy Goecks and Christopher Corless
The NCI, under the auspices of the Beau Biden Cancer Moonshot Initiative is promoting development of multidimensional molecular, cellular, and morphological mapping of human cancers. The OCSSB was accepted as a one of the Research Centers participating in the NCI Cancer Atlas Project Network. Our project, the Omic and Multidimensional Spatial (OMS) atlas, includes collaborators from Harvard Medical School and the MD Anderson Cancer Center and will develop "maps" of human metastatic breast cancers. Newly established, it will take advantage of the tissues and research and clinical infrastructure in the SMMART program (described below).
Clinical research trials for treatment-resistant breast cancers
Prospect Creek Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) program
Lead Investigators: Gordon Mills, Joe Gray, Raymond Bergan
The goal of this project is to make treatments of cancers of the breast, prostate, pancreas and AML more durable and more tolerable by uncovering and defeating mechanisms of resistance to chemotherapy—as they arise during treatment. In SMMART, patients are followed longitudinally and prescribed combination therapy of 33 FDA-approved drugs by a tumor board considering comprehensive molecular profiling of their tumors and functional assays indicating responsiveness of the patient’s tumor to SMMART drugs. The patient’s serial biopsies are also deeply characterized using a spectrum of omic and imaging analytics, with the purpose of discovering cancer mechanisms of resistance to treatment. All operational aspects of SMMART have been developed and optimized under the ongoing SMMART tissue acquisition protocol. The SMMART 1.0 interventional protocol passed CRRC review and will receive full IRB review once requested revisions are made to the patient consent forms, expected in June 2018. SMMART also includes rules-based precision medicine trials (referred to as SMMART 2.0). Patients have been entered and are receiving treatment (PARP inhibitor + immune modulator) in a SMMART TNBC study. Also, additional arms are being designed and planned (e.g., TNBC patients PARP + MEK inhibitor, PARP + PI3K inhibitor, etc.). Negotiations with pharma for drugs and funding have been successful to date and are continuing. This project is funded by a major philanthropic contribution from the Prospect Creek Foundation.
Understanding treatment-resistant breast cancers
NCI Cancer Systems Biology Center (CSBC) for Measuring, Modeling and Controlling Heterogeneity (M2CH)
Lead Investigators: Joe Gray, Rosalie Sears, Emek Demir and Claire Tomlin
The overall goal of the NCI Cancer Systems Biology Consortium (CSBC) is to increase our understanding of tumor biology, treatment options, and patient outcome by addressing the complexity associated with cancer through integration of experimental biology and computational and mathematical analysis. The OHSU Center for Cancer Systems Biology involves investigators at OHSU, UC Berkeley, and the MD Anderson Cancer Center. It is one of several NCI CSBC Centers. The goal of the OHSU Center is to improve management of triple negative breast cancer by developing systems level strategies to prevent the emergence of cancer subpopulations that are resistant to treatment. We postulate that heterogeneity arising from epigenomic instability intrinsic to cancer cells and diverse signals from extrinsic microenvironments in which cancer cells reside are root causes of resistance.
Characterization of cellular responses to chemical signals in the microenvironment
NIH Microenvironment Perturbagen LINCS Center
Lead Investigators: Joe Gray, Gordon Mills, Laura Heiser, James Korkola
The overall goal of the NIH Common Fund’s Library of Integrated Network-based Cellular Signatures (LINCS) program is to develop a “library” of molecular signatures that describes how different types of cells respond to a variety of perturbing agents. The OHSU LINCS Center was funded for six years in September 2014. It is one of 5 NIH LINCS Centers and involves investigators at OHSU, the MD Anderson Cancer Center and City of Hope. Our Center contributes to the overall LINCS effort by exploring how the biological behaviors of cells are influenced by the regulatory signals they receive from the microenvironments in which they reside.
State-of-the-art cryogenic electron microscopy
NIH National Cryo-EM Service Center - Pacific Northwest Center for Cryo-EM (PNCC)
Lead Investigator: Eric Gouaux, Craig Yoshioka, Claudia López, James Evans, Michael Chapman
The NIH has established the Pacific Northwest Center for Cryo-EM (PNCC), a collaboration between OHSU and PNNL, as one of three national cryo-EM service centers to provide access to the technology and support the development of cryo-EM training curricula to build a skilled work-force. The NIH notes that cryo-EM is a method used to image frozen biological molecules without the use of structure-altering dyes or fixatives or the need for crystallization to provide a more accurate model of the molecules and a greater understanding of biological function. Recent advances in cryo-EM technology have made it possible for scientists to obtain detailed images and structures of many biological molecules that cannot be obtained using other methods, like x-ray crystallography. The PNCC builds on the core cryo-EM capability established in the OCSSB and will provide scientists with access to state-of-the-art cryo-EM technology and training, from sample preparation to collection of high-resolution data and computational analysis.
Ongoing research projects
We have had ongoing relationships with many other centers and projects at OHSU, including:
- Brenden-Colson Center for Pancreatic Care, in which the work the OCSSB performs informs many aspects of their advanced treatments for pancreatic cancers
- Multiscale Microscopy Core (MMC), a university-wide core (or service facility) which is staffed by OCSSB faculty and researchers to provide training and services in electron microscopy (EM)
- Living Laboratory, which provides researchers with access to the same electron microscopy tools in the MMC but as part of research efforts to further refine advanced microscopy techniques
Ongoing research areas
Our researchers are involved in several general areas of research, many of which have applications in cancer biology:
- Chemical imaging, including reporter chemistry and chemical probes
- Molecular signaling
- Computational biology methods for systems biology
- Superresolution and multiscale microscopy methods