Research at the OCSSB
Overview
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.
Major projects
Prospect Creek SMMART Program
The goal of this project is to make treatments of cancers of the breast, prostate, pancreas and acute myeloid leukemia (also known as AML) more durable and more tolerable by countering mechanisms of resistance as they arise during treatment. This project is funded by a major philanthropic contribution from the Prospect Creek Foundation. Two initial proof of concept trials, SMMART-MMTERT and SMMART-Prime, as well as a third arm, SMMART-AMTEC, focused on breast cancer. Each of the SMMART studies have received IRB approval and patients are being recruited to two of the three trials. Preliminary data from the program is extremely exciting with a greater than 80% major benefit rate and a number of metastatic patients attaining complete responses. Negotiations with pharma for drugs and funding have been successful to date and are continuing.
National Cancer Institute M2CH Cancer Systems Biology Center
M2CH stands for Measuring, Modeling and Controlling Heterogeneity, a reference to our research goals in studying triple-negative breast cancer.
The M2CH is a National Cancer Institute, or NCI-designated research center of the Cancer Systems Biology Consortium (CSBC). The overall goal of the CSBC is to increase scientists' understanding of tumor biology, treatment options, and patient outcome. The CSBC aims to achieve this by addressing the complexity associated with cancer through integration of experimental biology and computational and mathematical analysis.
The M2CH involves investigators at OHSU (mainly the OCSSB), UC Berkeley, and the MD Anderson Cancer Center. It was funded for five years beginning in 2017 and is one of 13 NCI Centers that comprise the CSBC. The goal of the M2CH is to improve management of triple negative breast cancer by developing systems-level strategies to prevent or counter the emergence of cancer subpopulations that are resistant to treatment. We postulate that heterogeneity arising from genomic and epigenomic instability intrinsic to cancer cells and diverse signals from extrinsic microenvironments in which cancer cells reside are root causes of resistance.
National Institute of Health MEP LINCS Center
The overall goal of the National Institute of Health 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 six 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, or microenvironment perturbagens (MEP) in which they reside.
NCI OMS Human Tumor Atlas
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 OHSU Human Tumor Atlas Network Research Center was funded in 2018 for five years as part of this initiative and is one of five centers that comprise the Human Tumor Atlas Network. The OHSU center includes collaborators from Harvard Medical School and the MD Anderson Cancer Center. The goal of the OHSU center is to develop omic and multidimensional spatial atlases of metastatic breast cancers. It takes advantage of the tissues, research and clinical infrastructure in the OCSSB and the SMMART program.
Pacific Northwest Center for CryoEM (PNCC)
The National Institute of Health has established the Pacific Northwest Center for CryoEM (PNCC) as one of three national cryogenic electron microscopy, or cryoEM, service centers. The purpose of the cryoEM centers is to provide access to cryoEM technology and support the development of cryoEM training curricula to build a skilled workforce. This technology images frozen biological molecules to provide a more accurate model of the molecules and a greater understanding of biological function. The PNCC is jointly administered by OHSU and the Pacific Northwest National Laboratory (PNNL).
Recent advances in cryoEM 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 cryoEM capability established in the OCSSB and will provide scientists with access to state-of-the-art cryoEM technology and training, from sample preparation to collection of high-resolution data and computational analysis.
Areas of interest
Microscopy
Our microscopes are some of the world's most advanced, and our staff among those with the greatest expertise in their use that our facilities and our staff train other scientists both on campus and nationally. 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.
Faculty: Joe Gray, Catherine Galbraith, Summer Gibbs, Xiaolin Nan. Also see the Multiscale Microscopy Core.
Omics
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.
Faculty: Joe Gray. Also see SMMART, and About the OCSSB.
Cell microenvironment
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.
Faculty: Young Hwan Chang, Laura Heiser, Jim Korkola
Clinical trials
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.
Reporter chemistry and chemical imaging
We are exploring many areas of chemical imaging, mostly for cancer biology applications:
- Synthesis of novel fluorescent probes
- New technologies for mapping cellular proteins
- Fluorogenic sensors
- Fluorescent reporters for High Resolution Microscopy
- Fluorescence image-guided surgery
- Cyclic IF/IHC
- Fluorescently Labeled Small Molecule Therapeutics
- Click Chemistry applications in imaging and proteomics
Faculty: Kimberly Beatty, Summer Gibbs
Computational Modeling and Analysis
OCSSB scientists generate extremely large amounts of highly complex data, from imaging and other experimental platforms. Interpreting this data requires cutting-edge image analysis, physics-based modeling, and statistical computations. Machine learning methods and statistical physics approaches, along with molecular and cell modeling techniques, are particularly important.
Faculty: Young Hwan Chang, Daniel Zuckerman