Epigenetics of myeloid white blood cells

We study the fundamental biology of developing myeloid white blood cells and how these processes go awry in blood cancers. Our work is focused on the epigenetic processes that determine the fate of blood cells.

Subtle perturbation to these processes is the founding event in leukemia, often occurring years to decades before disease develops. Through studying these early events, we aim to develop strategies to intervene early in the course of disease and to treat people with advanced disease. Team leader: Ted Braun, M.D., Ph.D.

Cellular signaling

We are focused on the dynamics of inter and intracellular signaling in the tumor microenvironment. Signaling interactions between malignant and nonmalignant cells play a vital role in the pathogenesis and drug response of many types of cancer.

We use live-cell microscopy and fluorescent biosensors to measure single-tumor cell-signaling and gene expression dynamics in the context of novel tissue and tissue-like microenvironments we have developed.

By pairing these approaches with computation and quantitative modeling, we aim to better understand how these interactions contribute to single-cell heterogeneity and plasticity, cancer progression and drug response. Team leader: Alexander Davies, D.V.M., Ph.D.

T-cell subsets

Slow-growing polyps often precede colorectal cancer (CRC). Novel, noninvasive approaches are needed to screen and detect CRC earlier. Our team is interested in dissecting the T-cell subsets present in early colorectal lesions, their role in the progression from adenoma to carcinoma, and the possibility of detecting these cells in the blood of patients.

This work provides insight on the role of the immune system in recognizing and responding to neoantigen mutations and pathogenic or commensal bacteria in CRC. The earlier we can detect this immune response, the earlier we can interfere with the onset, development or recurrence of the cancer. Team leader: Rebekka Duhen, Ph.D.

Proteomics

We discover biomarkers using Seer’s Proteograph product suite, which is based on proprietary engineered nanoparticle technology. In combination with mass spectrometry analysis, this enables deep proteomic sampling of highly complex liquid biopsy specimen types, including plasma and serum, to be performed in highly scaled, large cohort studies.

CEDAR was the first client in the world to deploy Proteograph and its automated workflow. We have now initiated multiple studies using this technology to improve early cancer detection.

In one study, we are using this technology to interrogate over 900 patient serum specimens to identify new proteomic blood signatures in a major cancer indication. Team leader: Mark Flory, Ph.D.

PDAC biomarkers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer. There is an unmet need to develop a blood test to stratify patients with pancreatic cysts into categories of high-probability and low-probability for having PDAC, where high-probability patients would benefit from a tissue biopsy.

Currently, no blood-based PDAC biomarkers exist. Our research evaluates the efficacy of using biomarkers carried by tumor-derived exosomes to differentiate patients with pancreatic cancer from patients with benign pancreatic disease.

We use high conductance dielectrophoresis technology to recover these tumorderived nanoparticles from patient plasma. These particles offer a new source of potential PDAC biomarkers that could differentiate PDAC from benign pancreatic disease. Team leader: Stuart Ibsen, Ph.D.

Fibroblasts

The five-year survival rate for pancreatic cancer patients is only 10%, the lowest of all major cancers. There is an urgent need to understand the biology underlying pancreatic tumor development so that we can better prevent, detect and treat this disease.

Cells in the tumor microenvironment (TME) alter their phenotypes in response to new tumor growth, and these cells can play a critical role regulating early tumor development and progression to malignant disease. Using cell culture, mouse models and 3D bioprinted human tumor tissues, we interrogate how TME cells influence early pancreatic cancer development, with a particular interest in the role of cancer associated fibroblasts.

Our goal is to better understand the mechanisms of crosstalk and plasticity between neoplastic and non-neoplastic cells to identify and target the tumorpromoting functions of the TME. Team leader: Ellen Langer, Ph.D.

Cancer nanobiology

Cancer nanobiology is key to finding the earliest perturbations in tumor formation and proliferation. We use scanning electron microscopy on human tissue samples to view tumors and the surrounding microenvironment at high resolution, providing both subcellular detail with views of the macro-scale in the same image, forming a “Google Earth”-type map.

When coupled with a focused ion beam, we cut very thin slices (4 nm) from the tissue, image them at 4 nm/pixel, and slice again. Using thousands of images, we reconstruct three-dimensional models showing the most intimate spatial relationships of key subcellular structures and interactions between neighboring cells.

These models assist in linking tumor phenotype to genotype and clarify cellular structures that could be therapeutic targets. Team leader: Jessica Riesterer McQuiston, Ph.D.

Genetic and epigenetic insights into cellular dynamics

We seek to understand the fundamentals of epigenetic and transcriptional regulation in hormone-driven cancers such as breast and prostate cancer for early detection and treatment. Our research has two primary areas of interest:

• Proteomics approaches to investigate transcription factor complexes
• Single-cell multiomics approaches to connect underlying tumor heterogeneity with hormone response.

Team leader: Hisham Mohammed, Ph.D.

Tissue-resident lymphocytes

We are focused on the biology of tissue-resident lymphocytes and their role in cancer development. We’re looking at:

• Tissue-resident B cells.
• Inflammatory skin disease and cancer.
• Harnessing tissue-specific immune function to develop new immunotherapeutic and cancer detection tools

Team leader: Joshua Moreau, Ph.D.

Extracellular biomarkers

The extracellular group investigates technologies for diagnosis and prognosis of cancer, pre-cancer, pregnancy complications and other diseases by examining cell-free RNA, cell-free DNA and extracellular vesicles in body fluids. We develop and deploy technologies to expand the liquid biopsy toolbox for deep phenotype characterization at epigenetic, transcriptomic and proteomic levels.

We aim to identify molecular signatures and biological pathways associated with natural disease progression and treatment-induced responses, evolution and adaptation. We develop methods to analyze circulating cell-free RNA (cfRNA), multiplexed single extracellular vesicles (EVs) and epigenetic marks carried by cellfree nucleosomal DNA complexes.

We analyze longitudinal blood samples from patients and mice with liver diseases, hepatocellular carcinoma, pancreatic ductal adenocarcinoma and breast cancer. We apply machine learning to monitor disease progression, provide precise diagnoses, stratify treatment selection and predict treatment response. Team leader: Thuy Ngo, Ph.D.

Nuclear dynamics

We study how nuclear processes such as DNA replication, transcription and repair are coordinated during the cell cycle. We integrate powerful microscopy approaches with cutting-edge sequencing technologies to uncover the elegant and dynamic biology of chromatin and how it both controls and is controlled by the cell cycle. These dynamics become disrupted in cancer and destabilize genetic and epigenetic information resulting in cell lineage instability and malignant transformation. Team leader: Joshua Saldivar, Ph.D.

Energy-responsive biomaterials

We focus on developing energy-responsive biomaterial platforms for tumor modeling and regenerative medicine. We have a particular interest in materials that can be controlled remotely and noninvasively using ultrasound. Our efforts include developing dynamic tissue-engineered platforms to model cancer progression in response to oncogenic stimuli. We also engineer responsive biomaterial systems to guide tissue repair and regeneration. Our work lies at the intersection of nanomaterials design, tissue engineering, gene/drug delivery and ultrasound physics. We are committed to fostering a lab culture that supports diversity, equity and inclusion and training the next generation of scientists through dedicated mentorship. Team leader: Carolyn Schutt Ibsen, Ph.D.

Fluoresence microscopy

We have undertaken a large project to develop a digital spatial tissue section platform that will utilize next-generation sequencing readouts to quantify hundreds of biomarkers in parallel from a single tissue section. We believe this system will offer increased speed, lower costs, better normalization and a higher dynamic range than standard methods. Our ultimate goal is to implement this platform in a precision oncology setting. Team leader: Sean Speese, Ph.D.

Chromatin

We’re developing machine-learning algorithms to characterize the epigenomes, transcriptomes and 3D organization of chromatin in cancerous and healthy cells using single-cell multiomics data. We are interested in studying transcriptional regulation/misregulation through unsupervised identification of regulatory elements, transcription factor activity, structural variation and determinants of 3D genome folding. Our vision is to integrate multiple modalities into a holistic view of healthy and diseased cell states. Team leader: Galip Yardimci, Ph.D

Translational nanomaterials

Our research focuses on the development of translational nanomaterials for early cancer detection and therapy. One of our primary goals is developing ultrasoundresponsive nanoparticles as cavitation seeds for ultrasound imaging and therapy.

We use these robust and biodegradable nanoparticles for several applications, including background-free ultrasound imaging, targeted ablation of solid tumors, and amplification of circulating tumor DNA levels to improve liquid biopsy for cancer.

We are also interested in understanding the underlying mechanisms of tumor targeting and accumulation of nanomaterials. Recently, we discovered that selfassembled nanostructures of amphiphilic peptides could target a broad range of solid tumors by hitchhiking on lipoprotein trafficking pathways.

We are evaluating these nanomaterials in preclinical studies for image-guided surgery of high-grade gliomas and chemotherapy of breast and colon cancers. Team leader: Adem Yildirim, Ph.D.

Spatial and temporal imaging of the prostate tumor microenvironment

We investigate the impact of the prostate tumor microenvironment on cancer progression and metastasis to improve patient stratification in the clinic. We integrate biological, computational, and clinical approaches to enhance our understanding of the intercellular interactions in the prostate tumor microenvironment with the overarching goal of providing novel early detection and treatment options for patients. Our team develops and applies quantitative spatial approaches to map the dynamic cell-cell interactions in the prostate tumor microenvironment using longitudinal patient samples, providing a temporal map of tumor evolution.

One specific focus in our team is on cancer-neuron communication. Cancer is a systemic disease that involves continuous communication with the nervous system. We investigate the intricate mechanisms underlying the bidirectional communication between tumor-innervating neurons and prostate cancer cells, which drive metastasis. Leveraging spatial image analysis, co-culture models, live cell imaging, and structural biology, we aim to identify novel therapeutic targets to inhibit cancer-neuron crosstalk and metastasis.

Team Leader: Ece Eksi, Ph.D.

Healthy Oregon Project (HOP)

We helped launch the Healthy Oregon Project, an ambitious study to understand the causes of cancer and other diseases in Oregon residents. HOP has recruited more than 40,000 participants. With our partners, we perform germline sequencing on biological samples to identify people who are at increased risk of cancer or cardiovascular disease.

Alliance for Cancer Early Detection (ACED)

CEDAR is a founding partner of the International Alliance for Cancer Early Detection, an international partnership aimed at accelerating research in early detection. One of our projects is building an integrated data platform to provide access to research data across the alliance.

Clinical trials for early detection

We conduct clinical trials to advance new technology for early cancer detection; some of these trials have thousands of participants. We recruit people with cancer and without cancer. We also recruit people who undergo regular cancer screening using conventional methods.

Our partners include: GRAIL, Freenome Holdings, DELFI Diagnostics, Adela, Guardant Health and the University of Washington.

Our trials include Pathfinder 2, Project Danube, Sanderson, PROACT LUNG, CASCADE-LUNG, CAMPERR, SHIELD and PATROL.

Learn more about our clinical trials for cancer early detection.