CEDSS: Disseminated cell hybrids as biomarkers for cancer detection, prognosis and treatment response
Melissa Wong, Ph.D.
Associate Professor and Vice Chair
Department of Cell, Development and Cancer Biology
Program Co-Lead, Knight Cancer Institute
Oregon Health & Science University
Zoom Details
Meeting URL: https://stanford.zoom.us/s/98184098662
Dial: US: +1 650 724 9799 or +1 833 302 1536 (Toll Free)
Meeting ID: 981 8409 8662
Passcode: 084321
ABSTRACT
Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread. These disseminated hybrids outnumber conventionally defined circulating tumor cells (CTCs) in cancer patients. It is unknown if CHCs represent a generalized cancer mechanism for cell dissemination, or if this population is relevant to the metastatic cascade. We detect CHCs in the peripheral blood of patients with cancer in myriad disease sites encompassing epithelial and non-epithelial malignancies. Further, we demonstrate that in vivo-derived hybrid cells harbor tumor-initiating capacity in murine cancer models and that CHCs from human breast cancer patients express stem cell antigens, features consistent with the ability to seed and grow at metastatic sites. We reveal heterogeneity of CHC phenotypes reflect key tumor features, including oncogenic mutations and functional protein expression. Importantly, this novel population of disseminated neoplastic cells opens a new area in cancer biology and renewed opportunity for battling metastatic disease.
ABOUT
The research focus of the Wong laboratory revolves around understanding the regulatory mechanisms that control epithelial stem cell homeostasis and their expansion in developmental, homeostasis and disease contexts, including cancer. I have substantial training and experience in intestinal stem cell investigation leveraging in vivo and ex vivo modeling, as well as in myriad cutting edge technologies (i.e. cyCIF, scRNA-seq). My publication record spans my post-doctoral fellowship in Dr. Jeffrey Gordon’s laboratory at Washington University School of Medicine, to studies in my own laboratory at Oregon Health & Science University. Our research impacts the understanding of regulatory mechanisms that govern cell state in the context of the evolving tissue microenvironment and changing cell signaling landscape, in development and disease.
Our studies in stem cell regulation led to the intriguing finding that stem cells can fuse with tissue macrophages in the context of injury repair and may impact tissue regeneration. We have extended these findings to the cancer setting, where cancer-macrophage fusions are detectible in primary and metastatic tumors, and my group recently identified and characterized these cells as a novel circulating tumor cell population. Importantly, our studies in cell culture, in mice and humans provide an indepth evaluation of hybrid cells to set the foundation for continued investigations into their biology, impact on disease progression or tissue regeneration, and use as a biomarker for disease burden. Importantly, we coined the term, circulating hybrid cell (CHC) for this novel population and reported they exist at higher levels than conventionally defined circulating tumor cells in the peripheral blood of cancer patients. This work was published in 2018 and highlighted by Science Magazine as one of the top ten publications in the cancer field in the science family journals. The science proposed in this U01 application leverage hybrid cell biology to assess treatment response and resistance in breast cancer patients undergoing targeted therapy. Our proposal leverages active collaborations with Dr. Young Hwan Young’s group to synergize biology with computation, as well as a number of other valuable collaborators to ensure success of the proposed, cutting-edge science.
Hosted by: Utkan Demirci, Ph.D.
Sponsored by: The Canary Center & the Department of Radiology
Stanford University – School of Medicine
Radiology Department-Wide Research Meeting
• Dominik Fleischmann, MD: 3DQ Lab Overview
• Tom Soh, PhD: Research Updates
Location: Zoom – Details can be found here: https://radresearch.stanford.edu
Meetings will be the 3rd Friday of each month.
Hosted by: Brian Hargreaves, PhD
Sponsored by: the the Department of Radiology
MIPS Seminar Series: “Circulating Tumor DNA Biomarkers for Therapy Monitoring and Early Detection”
Shan X. Wang, PhD
Leland T. Edwards Professor in the School of Engineering
Professor of Materials Science & Engineering, jointly of Electrical Engineering, and by courtesy of Radiology (Stanford School of Medicine)
Director, Stanford Center for Magnetic Nanotechnology
Stanford University
Location: Zoom
Webinar URL: https://stanford.zoom.us/s/93202777468
Dial: +1 650 724 9799 or +1 833 302 1536
Webinar ID: 932 0277 7468
Passcode: 851144
12:00pm – 12:45pm Seminar & Discussion
RSVP Here
ABSTRACT
Inspired by Dr Sam Gambhir, MIPS, Canary Center, and Stanford CCNE have pursued in vivo imaging and in vitro diagnostic tests for cancer therapeutic response or early detection, respectively, over the last 15+ years. Here I present two successful examples based on circulating tumor DNA (ctDNA) targets in plasma, complementary to imaging modalities such as CT and Ultrasound.
We have developed a simple yet highly sensitive assay for the detection of actionable mutational targets such as Epidermal Growth Factor Receptor (EGFR) and Kirsten rat sarcoma oncogene (KRAS) mutations in the plasma ctDNA from non-small cell lung cancer (NSCLC) patients using giant magnetoresistive (GMR) nanosensors. Our assay achieves lower limits of detection compared to standard fluorescent PCR based assays, and comparable performance to digital PCR methods. In 30 patients with metastatic disease and known EGFR mutation status at diagnosis, our assay achieved 87.5% sensitivity for Exon19 deletion and 90% sensitivity for L858R mutation while retaining 100% specificity; additionally, our assay detected secondary T790M mutation resistance with 96.3% specificity while retaining 100% sensitivity. We re-sampled 13 patients undergoing tyrosine kinase inhibitor (TKI) therapy 2 weeks after initiation to assess response, our GMR assay was 100% accurate in correlation with longitudinal clinical outcome, and the responders identified by the GMR assay had significantly improved progression free survival (PFS) compared to the non-responders. The GMR assay is low cost, rapid, and portable, making it ideal for detecting actionable mutations at diagnosis and non-invasively monitoring treatment response in the clinic.
On another front, we have also developed a highly sensitive and multiplexed assay for the detection of methylated ctDNA targets in plasma samples. Current diagnostic tests for liver cancer in at-risk patients are cumbersome, costly and inaccurate, resulting in a need for accurate blood-based tests. By devising a Layered Analysis of Methylated Biomarkers (LAMB) from the relevant big data, we have discovered a set of DNA targets in the blood that accurately detects liver cancer in these at-risk patients. This set of methylated targets was found by analyzing the genetic information of 3411 liver cancer patients and 1722 healthy people. Our results could lead to clinical adoption of liquid biopsy tests for liver cancer surveillance in high-risk populations and the development of blood tests for other cancers.
ABOUT
Prof. Wang directs the Center for Magnetic Nanotechnology and is a leading expert in biosensors, information storage and spintronics. His research and inventions span across a variety of areas including magnetic biochips, in vitro diagnostics, cancer biomarkers, magnetic nanoparticles, magnetic sensors, magnetoresistive random access memory, and magnetic integrated inductors. He has over 300 publications, and holds 65 issued or pending patents in these and interdisciplinary areas. He was named an inaugural Fred Terman Fellow, and was elected a Fellow of the Institute of Electrical and Electronics Engineers (IEEE) and a Fellow of American Physical Society (APS) for his seminal contributions to magnetic materials and nanosensors. His team won the Grand Challenge Exploration Award from Gates Foundation (2010), the XCHALLENGE Distinguished Award (2014), and the Bold Epic Innovator Award from the XPRIZE Foundation (2017).
Dr. Wang cofounded three high-tech startups in Silicon Valley, including MagArray, Inc. and Flux Biosciences, Inc. In 2018 MagArray launched a first of its kind lung cancer early diagnostic assay based on protein cancer biomarkers and support vector machine (SVM). In 2019, Flux Biosciences launched a human trial to offer at-home testing of fertility based on hormones and magneto-nanosensors. Through his participation in the Center for Cancer Nanotechnology Excellence (as co-PI of the CCNE) and the Joint University Microelectronics Program (JUMP), he is actively engaged in the transformative research of healthcare and is developing emerging memories for energy efficient computing.
Hosted by: Katherine Ferrara, PhD
Sponsored by: Molecular Imaging Program at Stanford & the Department of Radiology
Radiology Department-Wide Research Meeting
• Research Announcements
• Michelle James, PhD – Detecting and Tracking Immune Responses in the Brain and Beyond using PET
• Ryan Spitler, PhD – Precision Health and Integrated Diagnostics (PHIND) Center
Location: Zoom – Details can be found here: https://radresearch.stanford.edu
Meetings will be the 3rd Friday of each month.
Hosted by: Brian Hargreaves, PhD
Sponsored by: the the Department of Radiology
MIPS Seminar Series: Emerging nanophotonic platforms for infectious disease diagnostics: Re-imagining the conventional microbiology toolkit
Jennifer Dionne, PhD
Senior Associate Vice Provost for Research Platforms/Shared Facilities
Associate Professor of Material Science and Engineering and, by courtesy, of Radiology (Molecular Imaging Program at Stanford)
Stanford University
Location: Zoom
Webinar URL: https://stanford.zoom.us/j/95883654314
Dial: +1 650 724 9799 or +1 833 302 1536
Webinar ID: 958 8365 4314
Passcode: 105586
12:00pm – 12:45pm Seminar & Discussion
RSVP Here
ABSTRACT
We present our research controlling light at the nanoscale for infectious disease diagnostics, including detecting bacteria at low concentration, sensing COVID gene sequences, and visualizing in-vivo inter-cellular forces. First, we combine Raman spectroscopy and deep learning to accurately classify bacteria by both species and antibiotic resistance in a single step. We design a convolutional neural network (CNN) for spectral data and train it to identify 30 of the most common bacterial strains from single-cell Raman spectra, achieving antibiotic treatment identification accuracies exceeding 99% and species identification accuracies similar to leading mass spectrometry identification techniques. Our combined Raman-CNN system represents a proof-of-concept for rapid, culture-free identification of bacterial isolates and antibiotic resistance. Second, we describe resonant nanophotonic surfaces, known as “metasurfaces” that enable multiplexed detection of SARS-CoV-2 gene sequences. Our metasurfaces utilize guided mode resonances excited in high refractive index nanostructures. The high quality factor modes produce a large amplification of the electromagnetic field near the nanostructures that increase the response to targeted binding of nucleic acids; simultaneously, the optical signal is beam-steered for multiplexed detection. We describe how this platform can be manufactured at scale for portable, low-cost assays. Finally, we introduce a new class of in vivo optical probes to monitor biological forces with high spatial resolution. Our design is based on upconverting nanoparticles that, when excited in the near-infrared, emit light of a different color and intensity in response to nano-to-microNewton forces. The nanoparticles are sub-30nm in size, do not bleach or photoblink, and can enable deep tissue imaging with minimal tissue autofluorescence. We present the design, synthesis, and characterization of these nanoparticles both in vitro and in vivo, focusing on the forces generated by the roundworm C. elegans as it feeds and digests its bacterial food.
ABOUT
Jennifer Dionne is the Senior Associate Vice Provost of Research Platforms/Shared Facilities and an associate professor of Materials Science and Engineering and, by courtesy, of Radiology at Stanford. She is also an Associate Editor of Nano Letters, director of the DOE-funded Photonics at Thermodynamic Limits Energy Frontier Research Center, and an affiliate faculty of the Wu Tsai Neurosciences Institute, the Institute for Immunity, Transplantation, and Infection, and Bio-X. Jen received her B.S. degrees in Physics and Systems Science and Mathematics from Washington University in St. Louis, her Ph. D. in Applied Physics at the California Institute of Technology in 2009, and her postdoctoral training in Chemistry at Berkeley. Her research develops nanophotonic methods to observe and control chemical and biological processes as they unfold with nanometer scale resolution, emphasizing critical challenges in global health and sustainability. Her work has been recognized with the Alan T. Waterman Award, a NIH Director’s New Innovator Award, a Moore Inventor Fellowship, the Materials Research Society Young Investigator Award, and the Presidential Early Career Award for Scientists and Engineers, and was featured on Oprah’s list of “50 Things that will make you say ‘Wow’!”. Beyond the lab, Jen enjoys exploring the intersection of art and science, long-distance cycling, and reliving her childhood with her two young sons.
Hosted by: Katherine Ferrara, PhD
Sponsored by: Molecular Imaging Program at Stanford & the Department of Radiology
Targeted violence continues against Black Americans, Asian Americans, and all people of color. The department of radiology diversity committee is running a racial equity challenge to raise awareness of systemic racism, implicit bias and related issues. Participants will be provided a list of resources on these topics such as articles, podcasts, videos, etc., from which they can choose, with the “challenge” of engaging with one to three media sources prior to our session (some videos are as short as a few minutes). Participants will meet in small-group breakout sessions to discuss what they’ve learned and share ideas.
Please reach out to Marta Flory, flory@stanford.edu with questions. For details about the session, including recommended resources and the Zoom link, please reach out to Meke Faaoso at mfaaoso@stanford.edu.
CEDSS: “Building a Scalable Clinical Genomics Program: How tumor, normal, and plasma DNA sequencing are informing cancer care, cancer risk, and cancer detection”
Elizabeth and Felix Rohatyn Chair & Associate Director of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology
Memorial Sloan Kettering Cancer Center
Zoom Details
Meeting URL: https://stanford.zoom.us/s/92559505314
Dial: US: +1 650 724 9799 or +1 833 302 1536 (Toll Free)
Meeting ID: 925 5950 5314
Passcode: 418727
11:00am – 12:00pm Seminar & Discussion
RSVP Here
ABSTRACT
Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of oncogenomic mutations that can be targeted therapeutically. To accelerate enrollment to clinical trials of molecularly targeted agents and guide treatment selection, we have established a center-wide, prospective clinical sequencing program at Memorial Sloan Kettering Cancer Center using a custom, paired tumor-blood normal sequencing assay (MSK-IMPACT), which we have used to profile more than 50,000 patients with solid tumors. Yet beyond just the characterization of tumor-specific alterations, the inclusion of blood DNA has readily enabled the identification of germline risk alleles and somatic mutations associated with clonal hematopoiesis. To complement this approach, we have also implemented a ‘liquid biopsy’ cfDNA panel (MSK-ACCESS) for cancer detection, surveillance, and treatment selection and monitoring. In my talk, I will describe the prevalence of somatic and germline genomic alterations in a real-world population, the clinical benefits of cfDNA assessment, and how clonal hematopoiesis can inform cancer risk and confound liquid biopsy approaches to cancer detection.
ABOUT
Michael Berger, PhD, holds the Elizabeth and Felix Rohatyn Chair and is Associate Director of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology at Memorial Sloan Kettering Cancer Center, a multidisciplinary initiative to promote precision oncology through genomic analysis to guide the diagnosis and treatment of cancer patients. He is also an Associate Attending Geneticist in the Department of Pathology with expertise in cancer genomics, computational biology, and high-throughput DNA sequencing technology. His laboratory is developing experimental and computational methods to characterize the genetic makeup of individual cancers and identify genomic biomarkers of drug response and resistance. As Scientific Director of Clinical NGS in the Molecular Diagnostics Service, he oversees the development and bioinformatics associated with clinical sequencing assays, and he helped lead the development and implementation of MSK-IMPACT, a comprehensive FDA-authorized tumor sequencing panel that been used to profile more than 60,000 tumors from advanced cancer patients at MSK. The resulting data have enabled the characterization of somatic and germline biomarkers across many cancer types and the identification of mutations associated with clonal hematopoiesis. Dr. Berger also led the development of a clinically validated plasma cell-free DNA assay, MSK-ACCESS, which his laboratory is using to explore tumor evolution, acquired drug resistance, and occult metastatic disease. He received his Bachelor’s Degree in Physics from Princeton University and his Ph.D. in Biophysics from Harvard University.
Hosted by: Utkan Demirci, Ph.D.
Sponsored by: The Canary Center & the Department of Radiology
Stanford University – School of Medicine
MIPS Special Seminar: Jubilant Biosys: Drug discovery and contract research services, from target discovery to candidate selection
Thomas Haywood, PhD
Head of International Radiochemistry Collaborations
Stanford University
Saurabh Kapure, MBA
Vice President, Business Development (USA & APAC)
Jubilant Biosys Limited
Jay Sheth, MBA
Manager Business Development, Drug Discovery Services, and CDMO
Jubilant Biosys Limited
LOCATION: Zoom
Meeting URL: https://stanford.zoom.us/j/98108346345
Dial: +1 650 724 9799 or +1 833 302 1536
Meeting ID: 981 0834 6345
Passcode: 397741
9:00-9:15 AM, PT – Thomas Haywood – Stanford Radiology projects
9:40-10:00 AM, PT – Moderated by Jason Thanh Lee – Discussion
ABOUT
Jubilant Biosys, an integrated contract research organization in India with business offices in Asia and North America, is a leading collaborator for biotechnology and pharmaceutical companies, with in-depth expertise in discovery informatics, medicinal chemistry, structural biology, and in vitro pharmacology services. Jubilant Biosys provides comprehensive drug discovery services and contract research services, from target discovery to candidate selection and with flexible business models (FFS, FTE and risk shared). This seminar will showcase case studies from recent Stanford projects and a discussion of future opportunities.
Sponsored by: Molecular Imaging Program at Stanford, Department of Radiology
Radiology Department-Wide Research Meeting
• Research Announcements
• Koen Nieman, M.D., PhD – Coronary Artery Disease by Computed Tomography
• Martin Willemink, M.D., PhD – Translating Emerging Cardiovascular CT Techniques into the Clinical Setting
Location: Zoom – Details can be found here: https://radresearch.stanford.edu
Meetings will be the 3rd Friday of each month.
Hosted by: Daniel Ennis, PhD
Sponsored by: the the Department of Radiology
MIPS Seminar Series: Image-guided focal therapy for prostate cancer
Geoffrey Sonn, MD
Assistant Professor of Urology and, by courtesy, of Radiology (Molecular Imaging Program at Stanford)
Stanford University Medical Center
Location: Zoom
Webinar URL: https://stanford.zoom.us/s/96126703618
Dial: +1 650 724 9799 or +1 833 302 1536
Webinar ID: 961 2670 3618
Passcode: 186059
12:00pm – 12:45pm Seminar & Discussion
RSVP Here
ABSTRACT
In recent years, prostate cancer treatment has increasingly focused on selecting patients who are most likely to benefit and reducing harms from treatment. This has been seen both in adoption of active surveillance for men with low-risk prostate cancer and emergence of image-guided focal ablative therapy. While focal therapy causes fewer sexual and urinary side effects than conventional prostate cancer treatments, many questions remain about proper patient selection, treatment planning, and follow up care.
Improvements in prostate MRI performance and interpretation have paved the way for adoption of focal therapy. However, clinical challenges remain in prostate cancer imaging. This talk will describe prostate cancer focal therapy, discuss patient selection, and highlight the research efforts of my group to improve MRI interpretation to guide biopsy and improve focal therapy performance.
ABOUT
Geoffrey Sonn, MD is a urologic oncologist who specializes in treating patients with prostate and kidney cancer. He has a particular interest in cancer imaging, MRI-Ultrasound fusion targeted prostate biopsy, prostate cancer focal therapy, and robotic surgery for prostate and kidney cancer. He is the principal investigator of the first clinical trial in Northern California to use MRI-guided focused ultrasound to treat prostate cancer. The goal of this trial is to treat prostate cancer with fewer side effects than surgery or radiation.
Dr. Sonn was born in Washington State and lived there until leaving for college at Georgetown. After graduating magna cum laude at Georgetown he returned to the West Coast for medical school at UCLA. Following medical school, Dr. Sonn completed a 6-year urology residency at Stanford where he developed particular interests in the clinical care of patients with urologic cancers and research in cancer imaging. Dr. Sonn completed a 2-year urologic oncology fellowship at UCLA. Since completing his fellowship, Dr. Sonn has been at Stanford as an assistant professor in urology. Dr. Sonn’s research is devoted to developing new cancer imaging techniques, applying artificial intelligence to find cancers on medical images, and applying new methods to treat prostate cancer with fewer side effects.
Hosted by: Katherine Ferrara, PhD
Sponsored by: Molecular Imaging Program at Stanford & the Department of Radiology