Using novel, cutting-edge technologies in biochemistry, imaging, and omics, we’re learning about normal and disease processes in the human body, in particular how a healthy person develops cancer. We want to use the knowledge we gain to help predict, prevent, and treat cancers, and develop treatments that are durable and tolerable. Personalized medicine, or precision oncology, is our next frontier.

Our microscopes are some of the world's most advanced, they are used to train other scientists around the country. We use many types of advanced microscopy, with a focus on the highest resolution electron microscopes. These allow us to see down to such small scales, we can literally visualize nanoscale features, measured in Ăngströms, such as those within individual molecules, in three dimensions.

Biochemical analyses specific to the sequencing of DNA, or genomics, is another area which we have explored and advanced to new levels. RNA sequencing, or transcriptomics, protein analysis, or proteomics, and other biochemical analyses of gene products is collectively referred to as omics, since these all involve the study of the overall products of a similar type of biological molecule (such as DNA, RNA, protein, or metabolites). Studying these in the contexts of healthy and diseased tissues tells us what is different in terms of genetics and biochemistry, between a normal and diseased cell. 

We are also examining the immediate environment, or microenvironment of cells because signals among cells and their environments shape their behavior, including how they grow and develop, or whether they halt their own processes. With this kind of information, we hope to understand how a normal cell might change into a tumor cell, and how a non-aggressive tumor cell could develop into an aggressive cancer cell.

Clinical trials are another, newer aspect of our research. The prospect of clinical trials not only may give patients the hope of novel treatments otherwise unavailable, but it gives researchers the ability to carefully study and follow a patient both before and after a trial of medication is given, in order to correlate the outcome with changes we can see through our biochemical, imaging and omics analyses. As there are many types of cancers, the goal is to tailor the treatments to an individual's specific cancer type, and also to that person's genomics. The aim is not only to control or cure cancers but to find treatments that are long-lasting, or durable, and allow a good quality of life, or are tolerable for the patient.

Major funded research projects

Using novel, cutting-edge technologies in biochemistry, imaging, and omics, we’re learning about normal and disease processes in the human body, in particular how a healthy person develops cancer. We want to use the knowledge we gain to help predict, prevent, and treat cancers, and develop treatments that are durable and tolerable. Personalized medicine, or precision oncology, is our next frontier.

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). 

Read more about the OMS Atlas project.

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.

Read more about the SMMART program.

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. 

Read more about M2CH.

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. 

Read more about MEP LINCS.

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:

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