MIPS Seminar Series: Translational Opportunities in Glycoscience
Carolyn Bertozzi, PhD
Director, ChEM-H
Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences
Professor, by courtesy, of Chemical and Systems Biology
Stanford University
Location: Zoom
Webinar URL: . https://stanford.zoom.us/j/94010708043
Dial: US: +1 650 724 9799 or +1 833 302 1536 (Toll Free)
Webinar ID: 940 1070 8043
Passcode: 659236
12:00pm – 12:45pm Seminar & Discussion
RSVP Here
ABSTRACT
Cell surface glycans constitute a rich biomolecular dataset that drives both normal and pathological processes. Their “readers” are glycan-binding receptors that can engage in cell-cell interactions and cell signaling. Our research focuses on mechanistic studies of glycan/receptor biology and applications of this knowledge to new therapeutic strategies. Our recent efforts center on pathogenic glycans in the tumor microenvironment and new therapeutic modalities based on the concept of targeted degradation.
ABOUT
Carolyn Bertozzi is the Baker Family Director of Stanford ChEM-H and the Anne T. and Robert M. Bass Professor of Humanities and Sciences in the Department of Chemistry at Stanford University. She is also an Investigator of the Howard Hughes Medical Institute. Her research focuses on profiling changes in cell surface glycosylation associated with cancer, inflammation and infection, and exploiting this information for development of diagnostic and therapeutic approaches, most recently in the area of immuno-oncology. She is an elected member of the National Academy of Medicine, the National Academy of Sciences, and the American Academy of Arts and Sciences. She also has been awarded the Lemelson-MIT Prize, a MacArthur Foundation Fellowship, the Chemistry for the Future Solvay Prize, among many others.
Hosted by: Katherine Ferrara, PhD
Sponsored by: Molecular Imaging Program at Stanford & the Department of Radiology
PHIND Seminar Series: Maternal Trauma History, Attachment Style, and Depression Are Associated with Broad DNA Methylation Signatures in Infants
Thalia Robakis, M.D., Ph.D.
Associate Professor
Department of Psychiatry
Mount Sinai School of Medicine
Location: Zoom
Webinar URL: https://stanford.zoom.us/s/95483174518
Dial: US: +1 650 724 9799 or +1 833 302 1536 (Toll Free)
Webinar ID: 954 8317 4518
Passcode: 179384
11:00am – 12:00pm Seminar & Discussion
RSVP Here
ABSTRACT
Background: The early environment provides many cues to young organisms that guide their development as they mature. Maternal personality and behavior are an important aspect of the environment of the developing human infant. The molecular mechanisms by which these influences are exerted are not well understood. We attempted to identify whether maternal traits could be associated with alterations in DNA methylation patterns in infants.
Methods: 32 women oversampled for history of depression were recruited in pregnancy and provided information on depressive symptoms, attachment style, and history of early life adversity. Buccal cell DNA was obtained from their infants at six months of age for a large-scale analysis of methylation patterns across 5×106 individual CpG dinucleotides, using clustering-based criteria for significance to control for multiple comparisons. Separately, associations between maternal depression, attachment style, and history of adversity and psychobehavioral outcomes in preschool-age children were examined.
Results: Tens of thousands of individual infant CpGs were alternatively methylated in association with each of the three studied maternal traits. Genes implicated in cell-cell communication, developmental patterning, growth, immune function/inflammatory response, and neurotransmission were identified. The result sets were highly coextensive among the three maternal traits, but areas of divergence exhibited intriguing parallels with behavioral outcomes.
Conclusions: Maternal personality traits are an important aspect of the infant environment that shapes offspring development in many ways. Infant genes that are epigenetically modified in reponse to maternal traits are potential candidate mediators for these effects. We have identified a large number of such genes and demonstrated parallels to clinically measurable outcomes in children.
ABOUT
Dr. Robakis is a psychiatrist with clinical and research interests in perinatal mood disorders and in the contribution of early life experiences to adult mental health and illness. She completed her M.D. as well as a Ph.D. in developmental neurobiology at Columbia University’s Medical Scientist Training Program, residency training in psychiatry at Stanford University School of Medicine, and a research fellowship in perinatal mood disorders also at Stanford. She remained on the clinical faculty at Stanford until 2019, when she accepted a position at the Icahn School of Medicine at Mount Sinai, where she is currently Associate Clinical Professor of Psychiatry and Assistant Director of the Women’s Mental Health Program.
Dr. Robakis’ research interests include the effects of early life stress and disordered attachment on risk for psychiatric illness in the perinatal period, on alterations in metabolism and cognition, and on psychobehavioral development in offspring. She is particularly interested in using epigenetic marks to help identify the biological pathways through which early life experiences exert their effects on outcomes in adulthood and intergenerationally.
Hosted by: Garry Gold, M.D.
Sponsored by the PHIND Center and the Department of Radiology
Imaging Immune Cell Modulation – MIPS Mini-Retreat
Hosted by: Dr. Katherine Ferrara, PhD
Sponsored by: Department of Radiology, Molecular Imaging Program at Stanford
The MIPS Mini-retreat series brings together members of the MIPS and greater School of Medicine community to discuss current opportunities for research and collaborations. Each month we will discuss a different topic and we invite all those interested to attend. The mini-retreats will be roughly 1.5-2 hours in length with ample time for discussion throughout. We hope you can join us and spark new collaborations!
Zoom Webinar Information
Webinar URL: https://stanford.zoom.us/j/94969801773
Dial: US: +1 650 724 9799 or +1 833 302 1536 (Toll Free)
Webinar ID: 949 6980 1773
Passcode: 292995
Agenda (all times are in PST)
8:00-8:05 AM – Opening Remarks – Katherine Ferrara, PhD
8:05-8:25 AM – Imaging CAR-T cells – Clinical Need – Crystal Mackall, MD
8:25-8:45 AM – Imaging Immune Cells in Cancer – Clinical Need – Ronald Levy, MD
8:45-9:05 AM – Imaging Approaches – Anna Wu, PhD
9:05-10:00 AM – Discussion – Moderated by: Katherine Ferrara, PhD
Amber Simpson, PhD
Canada Research Chair in Biomedical Computing and Informatics
Associate Professor in the School of Computing
and Department of Biomedical and Molecular Sciences
Queen’s University
Title:
Solving Fundamental Cancer Problems with Artificial Intelligence
Abstract:
Precision medicine is an approach to patient care that considers individual differences in a patient’s genetic and molecular makeup to predict disease progression and optimize treatment response – and one of the greatest opportunities, and challenges, in modern cancer care. There is currently no known method to predict the metastatic potential of any cancer at early stages. We propose to address this critical barrier by creating a cancer digital twin, a digital replica of a cancer patient using state-of-the-art artificial intelligence (AI) techniques applied to 900,000 abdominal CT scans from a high-volume cancer center. Predicting metastatic progression at early stages would radically transform our approach to cancer treatment, but promises substantial implications for patients and society that must be considered. For example, would you want to know a dismal prognosis predicted by your digital twin? How would you act on this information – would you regard the choice as yours, or your fate as given by your twin? In a world where AI is increasingly biased, how do we ensure that AI doesn’t create further inequities? Dr. Simpson will present new work on the development of a cancer twin for predicting metastatic progression as well as provide some discussion of the social ramifications of such technology.
Bio: Amber Simpson is the Canada Research Chair in Biomedical Computing and Informatics, and Associate Professor jointly appointed in the Department of Biomedical and Molecular Sciences and School of Computing at Queen’s University. She is an Affiliate of the Vector Institute for AI as well as a Senior Investigator at the Canadian Cancer Trials Group. She received her PhD in Computer Science from Queen’s and was a postdoctoral fellow in the Department of Biomedical Engineering at Vanderbilt University. Recently recruited from a faculty position at Memorial Sloan Kettering Cancer Center in New York, she holds research funding from the National Institutes of Health as well funding from all three Canadian research councils (Social Sciences and Humanities Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, and Canadian Institutes of Health Research). Dr. Simpson is an American Association of Cancer Research and Pancreatic Cancer Action Network award holder and a charter member of NIH study section, which recognizes her innovations in biomedical research. Dr. Simpson is the new director of the Human Mobility Research Centre, a centre that will be expanded to focus on health data innovations.
Radiology Department-Wide Research Meeting
Location: Zoom – Details can be found here: https://radresearch.stanford.edu
Meetings will be the 3rd Friday of each month.
February 19 Speakers:
Bruce Daniel, MD – Center Overview: IMMERS
Jennifer McNab, PhD – Encoding and Decoding Diffusion MRI
Hosted by: Brian Hargreaves, PhD
Sponsored by: the the Department of Radiology
MIPS Seminar Series: “Convergent, translational research to improve human health”
Joseph M. DeSimone, PhD
Sanjiv Sam Gambhir Professor of Translational Medicine and Chemical Engineering
Departments of Radiology and Chemical Engineering
Graduate School of Business (by Courtesy)
Stanford University
Location: Zoom
Webinar URL: https://stanford.zoom.us/s/98460805010
Dial: +1 650 724 9799 or +1 833 302 1536
Webinar ID: 984 6080 5010
Passcode: 809226
12:00pm – 12:45pm Seminar & Discussion
RSVP Here
ABSTRACT
In many ways, manufacturing processes define what’s possible in society. Central to our interests in the DeSimone laboratory are opportunities to make things using cutting-edge fabrication technologies that can improve human health. This lecture will describe advances in nano- / micro-fabrication and 3D printing technologies that we have made and employed toward this end. Using novel perfluoropolyether materials synthesized in our lab in 2004, we invented the Particle Replication in Non-wetting Templates (PRINT) technology, a high-resolution imprint lithography-based process to fabricate nano- and micro-particles with precise and independent control over particle parameters (e.g. size, shape, modulus, composition, charge, surface chemistry). PRINT brought the precision and uniformity associated with computer industry manufacturing technologies to medicine, resulting in the launch of Liquidia Technologies (NASDAQ: LQDA) and opening new research paths, including to elucidate the influence of specific particle parameters in biological systems (Proc. Natl. Acad. Sci. USA 2008), and to reveal insights to inform the design of vaccines (J. Control. Release 2018), targeted therapeutics (Nano Letters 2015), and even synthetic blood (PNAS 2011). In 2015, we reported the invention of the Continuous Liquid Interface Production (CLIP) 3D printing technology (Science 2015), which overcame major fundamental limitations in polymer 3D printing—slowness, a very limited range of materials, and an inability to create parts with the mechanical and thermal properties needed for widespread, durable utility. By rethinking the physics and chemistry of 3D printing, we created CLIP to eliminate layer-by-layer fabrication altogether. A rapid, continuous process, CLIP generates production-grade parts and is now transforming how products are manufactured in industries including automotive, footwear, and medicine. For example, to help address shortages, CLIP recently enabled a new nasopharyngeal swab for COVID-19 diagnostic testing to go from concept to market in just 20 days, followed by a 400-patient clinical trial at Stanford. Academic laboratories are also using CLIP to pursue new medical device possibilities, including geometrically complex IVRs to optimize drug delivery and implantable chemotherapy absorbers to limit toxic side effects. Vast opportunities exist to use CLIP to pursue next-generation medical devices and prostheses. Moreover, CLIP can improve current approaches; for example, the fabrication of an iontophoretic device we invented several years ago (Sci. Transl. Med. 2015) to drive chemotherapeutics directly into hard-to-reach solid tumors is now being optimized for clinical trials with CLIP. New design opportunities also exist in early detection, for example to improve specimen collection, device performance (e.g. microfluidics, cell sorting, supporting growth and studies with human organoids), and imaging (e.g. PET detectors, ultrasound transducers). Here at Stanford, we are pursuing new 3D printing advances, including software treatment planning for digital therapeutic devices in pediatric medicine, as well as the design of a high-resolution printer capable of single-digit micron resolution to advance microneedle designs as a potent delivery platform for vaccines. The impact of our work on human health ultimately relies on our ability to enable a convergent research program to take shape that allows for new connections to be made among traditionally disparate disciplines and concepts, and to ensure that we maintain a consistent focus on the translational potential of our discoveries and advances.
ABOUT
Joseph M. DeSimone is the Sanjiv Sam Gambhir Professor of Translational Medicine and Chemical Engineering at Stanford University. He holds appointments in the Departments of Radiology and Chemical Engineering with a courtesy appointment in Stanford’s Graduate School of Business. Previously, DeSimone was a professor of chemistry at the University of North Carolina at Chapel Hill and of chemical engineering at North Carolina State University. He is also Co-founder, Board Chair, and former CEO (2014 – 2019) of the additive manufacturing company, Carbon.
DeSimone is responsible for numerous breakthroughs in his career in areas including green chemistry, medical devices, nanomedicine, and 3D printing, also co-founding several companies based on his research. He has published over 350 scientific articles and is a named inventor on over 200 issued patents. Additionally, he has mentored 80 students through Ph.D. completion in his career, half of whom are women and members of underrepresented groups in STEM. In 2016 DeSimone was recognized by President Barack Obama with the National Medal of Technology and Innovation, the highest U.S. honor for achievement and leadership in advancing technological progress. He is also one of only 25 individuals elected to all three branches of the U.S. National Academies (Sciences, Medicine, Engineering). DeSimone received his B.S. in Chemistry in 1986 from Ursinus College and his Ph.D. in Chemistry in 1990 from Virginia Tech.
Hosted by: Katherine Ferrara, PhD
Sponsored by: Molecular Imaging Program at Stanford & the Department of Radiology
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
Geert Litjens, PhD
Assistant Professor in Computational Pathology
Department of Pathology
Radboud University Medical Center
Title: Going Beyond What is Humanly Possible: Machine Learning for Clinical Pathology
Abstract: Machine learning advances in the past decade have revolutionized computer vision, and have since also made their way into medical imaging. Although many associate medical imaging with radiology first, clinical pathology might be more significantly impacted, at least in the short term by machine learning. Partly due to the simultaneous advent of machine learning in medicine and digital pathology, but perhaps mostly because in pathology achieving inhuman feats is surprisingly low-hanging fruit. In this presentation, I will give some examples analog to radiology, then illustrate some superhuman applications. Subsequently, I will highlight our current limitations and possible future research directions.
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
Join us for the annual Precision Health & Integrated Diagnostics Symposium. This all-day virtual event will showcase the exciting PHIND work that is going on campus wide. The featured presentations will be from current PHIND investigators and Precision Health experts. We hope you can join us and look forward to building the PHIND community together.