Calendar

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
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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
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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

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

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
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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

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
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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

PHIND Seminar Series: Impact of the Veterans Affairs National Abdominal Aortic Screening Program

Manuel Garcia-Toca, M.D.
Clinical Professor of Surgery
Chief, Division of  Vascular Surgery
Santa Clara Valley Medical Center (SCVMC)

Oliver O. Aalami, M.D.
Clinical Associate Professor of Surgery, Vascular Surgery
Lucile Packard Children’s Hospital

Location: Zoom
Webinar URL: https://stanford.zoom.us/s/98417624095
Dial: US: +1 650 724 9799  or +1 833 302 1536 (Toll Free)
Webinar ID: 984 1762 4095
Passcode: 111283

11:00am – 12:00pm Seminar & Discussion
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ABSTRACT

Background: The U.S. Federal Government enacted the Screen for Abdominal Aortic Aneurysms Very Efficiently Act in January 2007. Simultaneously, the Department of Veterans Affairs (VA) implemented a more inclusive AAA screening policy for veteran beneficiaries shortly afterwards.

Our study aimed to evaluate the impact of the VA program on AAA detection rate and all-cause mortality compared to a cohort of patients whose aneurysms were identified by other abdominal imaging.

Methods: We identified veterans with an AAA screening study using the two existing Current Procedural Terminology (CPT) codes (G0389 and 76706).  In the comparison group, eligible abdominal imaging studies included ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) queried according to CPT codes between 2001 and 2018.

We used a difference-in-differences regression model to evaluate the change in aneurysm detection rate and all-cause mortality five years before and eleven years after the VA implemented the screening policy in 2007.

We calculated survival estimates after AAA screening or non-screening imaging of patients with or without AAA diagnosis and used multivariate Cox regression model to evaluate mortality in patients with a positive AAA diagnosis adjusting for patient characteristics and comorbidities.

Results: We identified 3.9 million veterans with abdominal imaging, a total of 303,664 of whom were coded has having an AAA US screening between 2007 and 2018. An AAA diagnosis was made in 4.84% of the screening group vs. 1.3% in the non-screening imaging group P<0.001, yet more aneurysms were found with general imaging studies (50,730 vs.15,449) (Fig 1).

On Kaplan-Meier survival analysis, patients with an AAA diagnosis had higher overall mortality than patients who screened normal; patients with aneurysms found with non-screening imaging had the highest mortality, log-rank P<0.001 (Fig 2).

The difference in differences regression analysis, showed that the absolute AAA detection rate was 1.55% higher (95% CI 1.2- 1.8), and the mortality was 13.89 % lower (95% CI 10.18 %-16.66 %) after the introduction of the screening program in 2007.

Multivariate Cox regression analysis in patients with AAA diagnosis (65-74-year-old) demonstrated a significantly lower 5-year mortality [HR 0.45 (95% CI 0.43-0.48)] for patients in the US Screening group P<0.001.

Conclusions: In a nationwide analysis of VA patients, implementation of AAA screening was associated with improved survival and a higher rate of AAA diagnosis. These findings provide further support for this program’s continuation versus defaulting to incidental recognition following other abdominal imaging.

ABOUT MANUEL GARCIA-TOCA
Dr. Garcia-Toca earned his medical degree at the Universidad Anahuac in Mexico 1999. He has a master’s degree in Health Policy from Stanford University.

He received his general surgery training at the Massachusetts General Hospital and Brown University in 2008. He then completed a Vascular Surgery fellowship at Northwestern University in 2010. Dr. Garcia-Toca is board certified in both surgery and vascular surgery.

Dr. Garcia-Toca joined Stanford Vascular Surgery in 2015. He is currently Clinical Professor of Surgery in the Division of Vascular Surgery. Dr. Garcia-Toca had previously served as an Assistant Professor of Surgery at Brown University.  Dr. Garcia Toca is a Staff Surgeon at Santa Clara Valley Medical Center in San Jose.

His research interests include new therapeutic strategies and outcomes for the management of vascular trauma, cerebrovascular diseases, dialysis access, aortic dissection and aneurysms.

ABOUT OLIVER O. AALAMI
Dr. Aalami is a Clinical Associate Professor of Vascular & Endovascular Surgery at Stanford University and the Palo Alto VA and serves as the Lead Director of Stanford’s Biodesign for Digital Health. He is the course director for Biodesign for Digital Health,  Building for Digital Health and co-founder of the open source project,  CardinalKit, developed to support sensor-based mobile research projects.  His primary research focuses on clinically validating the sensors in smartphones and smartwatches in patients with cardiovascular disease to further precision health implementation.

Hosted by: Garry Gold, M.D.
Sponsored by the PHIND Center and 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
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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.

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

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