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
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
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
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
Join us for the 11th biennial International Conference on Functional Imaging and Modeling of the Heart (FIMH). FIMH-2021 will celebrate 20 years of bringing together friends, colleagues, and collaborators to share and discuss the latest in cardiac and cardiovascular imaging, electrophysiology, computational modeling, and translational applications. The event will take place June 21-25, 2021 virtually, via Livestream, Zoom meeting workshops, and Spatial Chat networking.
Sponsored by: Functional Imaging and Modeling of the Heart Conference
Radiology Department-Wide Research Meeting
• Research Announcements
• Mirabela Rusu, PhD – Learning MRI Signatures of Aggressive Prostate Cancer: Bridging the Gap between Digital Pathologists and Digital Radiologists
• Akshay Chaudhari, PhD – Data-Efficient Machine Learning for Medical Imaging
Location: Zoom – Details can be found here: https://radresearch.stanford.edu
Meetings will be the 3rd Friday of each month.
Hosted by: Kawin Setsompop, PhD
Sponsored by: the the Department of Radiology
Dr. Sanjiv Sam Gambhir was a visionary who had a profound impact on the world of science and humanity. As a leader and pioneer in the fields of molecular imaging, early detection of cancer, and precision health, his enduring legacy can be seen in the research and innovations continuing in these fields today.
The Gambhir Symposium aims to celebrate Dr. Gambhir’s illustrious career and continue down the paths he forged by highlighting the work still ongoing in the fields he helped to cultivate. Join us to hear researchers and collaborators share current thoughts and future outlooks on topics developed with Sam.
We hope you can join us for the 2021 Virtual Gambhir Symposium.
The event is fully virtual and the livestream link will be posted on the website closer to the event.
Sponsored by: Department of Radiology at Stanford
Stanford AIMI Director Curt Langlotz and Co-Directors Matt Lungren and Nigam Shah invite you to join us on August 3 for the 2021 Stanford Center for Artificial Intelligence in Medicine and Imaging (AIMI) Symposium. The virtual symposium will focus on the latest, best research on the role of AI in diagnostic excellence across medicine, current areas of impact, fairness and societal impact, and translation and clinical implementation. The program includes talks, interactive panel discussions, and breakout sessions. Registration is free and open to all.
Also, the 2nd Annual BiOethics, the Law, and Data-sharing: AI in Radiology (BOLD-AIR) Summit will be held on August 4, in conjunction with the AIMI Symposium. The summit will convene a broad range of speakers in bioethics, law, regulation, industry groups, and patient safety and data privacy, to address the latest ethical, regulatory, and legal challenges regarding AI in radiology.