Alex K. Shalek, PhD
Pfizer-Laubach Career Development Associate Professor
Institute for Medical Engineering & Science
Department of Chemistry and Koch Institute
Massachusetts Institute of Technology
Abstract: While several methods exist for sampling tissues in clinical contexts, without high-fidelity tools for comprehensively profiling them, we are both limited in our capacity to understand how constituent cells and their interactions impact prognosis, and to select and develop precision therapeutics. Recent years have witnessed transformative and intersecting advances in nanofabrication and molecular biology that now enable deep profiling of low-input samples. Collectively, these afford new and exciting opportunities to study cellular heterogeneity, starting from the level of the single cell, and may unlock the diagnostic, prognostic, and discovery potential of clinical isolates. Illustratively, I will introduce how we can leverage single-cell genomic approaches – and, in particular, single-cell RNA-Seq – to explore the extensive functional diversity between cells, uncovering, from the “bottom-up,” distinct cell states and their molecular drivers. Moreover, I will discuss high-throughput experimental strategies and demonstrate, in the context of Acute Lymphoblastic Leukemia, how they can be leveraged to achieve the statistical power necessary to reconstruct intracellular circuits, enumerate and redefine cell states and types, and transform our understanding of cellular decision-making in health and disease on a genomic scale.
Bio: Alex K. Shalek is currently the Pfizer-Laubach Career Development Associate Professor at MIT, as well as a Core Member of the Institute for Medical Engineering and Science (IMES), an Associate Professor of Chemistry, and an Extramural Member of The Koch Institute for Integrative Cancer Research. He is also an Institute Member of the Broad Institute, an Associate Member of the Ragon Institute, an Assistant in Immunology at MGH, and an Instructor in Health Sciences and Technology at HMS. His research is directed towards the development and application of new technologies that facilitate understanding of how cells collectively perform systems-level functions in healthy and diseased states. Dr. Shalek received his bachelor’s degree summa cum laude from Columbia University and his Ph.D. from Harvard University in chemical physics under the guidance of Hongkun Park, and performed postdoctoral training under Hongkun Park and Aviv Regev (Broad/MIT). To date, his interdisciplinary research has focused on realizing and utilizing nanoscale manipulation and measurement technologies to examine how small components (molecules, cells) drive systems of vast complexity (cellular responses, population behaviors).
Cancer Early Detection Seminar
“Best Practices in Hip Imaging”
Michael Shen, PhD
Professor of Medicine, Genetics and Development, Urology and Systems Biology
Columbia University Medical Center
ABSTRACT
TBD
_____________________________________________
Hosted by
Sanjiv Sam Gambhir, MD, PhD<https://med.stanford.edu/profiles/sanjiv-gambhir>
Sponsored by
The Canary Center and the Stanford Cancer Institute
Stanford University
If you would like to be included on the email distribution list for weekly reminders, contact Ashley Williams (ashleylw.at.stanford.edu)
RSVP and more info at: https://www.onlineregistrationcenter.com/register/222/page1.asp?m=298&c=41
CEDSS: “Strategies to Identify Aggressive Breast Cancer Biology in Black and Latina Women”
Victoria Seewaldt, MD
Ruth Ziegler Professor and Chair, Department of Population Sciences
Associate Director for Population Sciences Research, Comprehensive Cancer Center
City of Hope
Beckman Center, Munzer Auditorium (B060)
11:00am – 12:00pm Seminar & Discussion
12:00pm – 12:15pm Reception & Light Refreshments
RSVP here: https://www.onlineregistrationcenter.com/VictoriaSeewaldt
ABSTRACT
Over 90% of breast cancer is cured; yet there remain highly aggressive breast cancers that develop rapidly and are extremely difficult to treat, much less prevent. Examples are triple-negative breast cancer in Black/African American women and luminal B breast cancers in Black/African Americans and Latinas. Breast cancers that rapidly develop between breast imaging are called “interval cancers”. Here we aim to investigate biologically aggressive precancerous breast lesions and their matched invasive breast cancers in women of diverse race and ethnicity. Our team has the unique ability to perform single cell in situ transcriptional profiling in combination with dynamic and spatial genomics/proteomics; this allows us to identify multi-dimensional spatial and temporal relationships that drive the transition from biologically aggressive pre-cancer to interval breast cancer.
ABOUT
Victoria Seewaldt, M.D., is an accomplished clinician and researcher who’s devoted to improving the lives of her patients and the community at large. She has led community outreach education efforts on cancer prevention through personal wellbeing and directed research aimed at finding biomarkers that can be used for early cancer detection, particularly triple-negative breast cancers that are especially resistant to treatment.
At City of Hope, Dr. Seewaldt will direct efforts to provide breast cancer education, free breast cancer screening and treatment, mentorship of young minority scholars, and a forum for community partnered trials. Clinically, Dr. Seewaldt aims to empower women at high breast cancer risk to be full partners in developing wellness strategies to promote personal health.
Dr. Seewaldt received her medical degree from the University of California, Davis, and completed her residency and clinical fellowship at the University of Washington in Seattle. She then pursued a medical oncology fellowship with the Fred Hutchinson Cancer Research Center and then became an assistant professor at Ohio State University. Afterwards, she transferred to Duke University, where she held various clinical, academic and leadership roles in its School of Medicine and Comprehensive Cancer Center — most recently as a professor, co-leader of the breast and ovarian cancer program and head of the cancer breast prevention program — before joining City of Hope.
Please note this seminar is now cancelled and will be rescheduled for a future date. Please contact Ashley Williams (ashleylw@stanford.edu) with any questions or concerns. Thank you for your understanding!
CEDSS: “The First Cell and the Human Cost of going after Cancer’s last”
Chan Soon-Shiong Professor of Medicine
Director, Myelodysplastic Syndrome Center
Columbia University Medical Center
CEDSS: “Multicancer detection of early-stage cancers with simultaneous tissue localization using a plasma cfDNA-based targeted methylation assay”
Eric Fung, M.D., Ph.D.
Senior Medical Director
GRAIL, Inc.
Please see zoom details below:
Meeting URL: https://stanford.zoom.us/j/230531527
Dial: +1 650 724 9799 (US, Canada, Caribbean Toll) or +1 833 302 1536 (US, Canada, Caribbean Toll Free)
Meeting ID: 230 531 527
ABOUT
Dr. Eric Fung is Vice President, Clinical Development at GRAIL, where he leads several clinical development programs in support of the development of a blood-based multi-cancer detection test. Dr. Fung has previously held clinical development and R&D leadership roles at Affymetrix, Vermillion, Ciphergen, and Roche Molecular Diagnostics. Dr. Fung has led clinical trials leading to FDA clearance of multiple IVD products. Dr. Fung received his MD, PhD from the Johns Hopkins University School of Medicine.
Hosted by: Sanjiv Sam Gambhir, M.D., Ph.D.
Sponsored by the Canary Center & the Department of Radiology
Stanford University – School of Medicine
CEDSS: “The Origins and Detection of Lethal Prostate Cancer”
Paul Boutros, Ph.D., M.B.A.
Director, Cancer Data Sciences
UCLA
Please see zoom details below:
Meeting URL: https://stanford.zoom.us/s/93515779500
Dial: +1 650 724 9799 or +1 833 302 1536
Meeting ID: 935 1577 9500
Meeting Passcode: 767148
ABOUT
Boutros earned his B.Sc. degree from the University of Waterloo in Chemistry in 2004, and his Ph.D. degree from the University of Toronto, Canada, in Medical Biophysics in 2008. At Toronto, he also earned an executive M.B.A. from the Rothman School of Management. In 2008, Boutros started his independent research career at the Ontario Institute for Cancer Research first as a fellow (2008–2010) and then as principal investigator (2010–2018). He moved to California to join the UCLA faculty in 2018.
Hosted by: Utkan Demirci, Ph.D.
Sponsored by the Canary Center & the Department of Radiology
Stanford University – School of Medicine
CEDSS: Systematic identification of fluid-based biomarkers for ovarian and prostate cancer
Thomas Kislinger, Ph.D.
Professor & Chair
Department of Medical Biophysics
University of Toronto
Senior Scientist
Princess Margaret Cancer Centre
Zoom Webinar Details
Meeting URL: https://stanford.zoom.us/s/94878578384
Dial: +1 650 724 9799 or +1 833 302 1536
Webinar ID: 948 7857 8384
Passcode: 692692
Register Here
ABOUT
Thomas Kislinger received his MSc in Analytical Chemistry from the University of Munich, Germany (1998). He completed his PhD in 2001, investigating the role of Advanced Glycation Endproducts in diabetic vascular complications at the University of Erlangen, Germany and Columbia University, New York. Between 2002 and 2006 he completed a post-doctoral fellowship at the University of Toronto. In 2006 he joined the Princess Margaret Cancer Centre as an independent investigator. Dr. Kislinger holds positions as Senior Scientist at the Princess Margaret Cancer Centre and as Professor and Chair at the University of Toronto in the Department of Medical Biophysics. The Kislinger lab applies proteomics technologies to translational and basic cancer biology. This includes the development of novel proteomics methodologies, identification of liquid biopsy signatures and the molecular identification of novel cell surface markers.
Hosted by: Utkan Demirci, Ph.D.
Sponsored by: The Canary Center & the Department of Radiology
Stanford University – School of Medicine
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
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