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The 2021 Gambhir Symposium (virtual) –celebrating ongoing work of visionary and pioneer Dr. Sanjiv Sam Gambhir

August 6, 2021

The 2021 Gambhir Symposium (virtual) held on July 19, 2021 included discussions and presentations celebrating the continuing work on paths forged by Sanjiv Sam Gambhir, MD, PhD, (1962-2020) in the fields in which he launched new directions:
Molecular Imaging, Cancer Early Detection, Precision Health.

Click Here to see the Conference Agenda & Videos.

Click here to see the videos from the Cancer Early Detection Session.

2021 Virtual PHIND Symposium

April 13, 2021

Dr. DeSimone gestures wearing an Oura monitoring ring, which made the news recently as the company partnered with the National Basketball Association (NBA) to help monitor the health of players.

The 2021 Precision Health and Integrated Diagnostics (PHIND) Center at Stanford held the virtual PHIND Symposium on March 23, 2021. The event showcased the exciting PHIND work that is going on campus-wide, featuring current PHIND investigators and Precision Health experts. Professor of Radiology Dr. Garry Gold gave an update on the PHIND center, reflecting upon former Radiology Chair Dr. Sanjiv Sam Gambhir’s visionary leadership and the continuation of this work, now with Dr. Gold’s direction, aimed at monitoring health to identify early transitions from health to disease.

Discussions included one with Dr. Joseph DeSimone, recently named recipient of the Sanjiv Sam Gambhir Professorship in Translational Medicine, who stated that although he is new to PHiND, his group has been thinking about precision delivery, using new devices such as microneedles to deliver treatments locally, rather than systemically throughout the body. Dr. Utkan Demirci, leading the Canary Center at Stanford, discussed his group’s Exosome-Total-Isolation-Chip (ExoTIC) device for identification of exosome-based biomarkers for monitoring health from a variety of biological fluids.

Besides devices, like the one in the picture, there was a focus on data. What kinds of data are we capturing as the clinical enterprise has transformed through Covid and telehealth? Can we separate patients into cohorts with online and in person visits to optimize the clinical workflows? How can we access and mine data from non-identifiable electronic health records? Participants also discussed ways to ensure equity in access to these devices and data, as well as ways to ensure clinical trial participants are engaged in meaningful ways in monitoring their health.

The Precision Health and Integrated Diagnostics Center (PHIND) at Stanford is dedicated to longitudinal monitoring and improvement of overall human health on a lifelong basis. Stanford advancements in biology and technology are leading to the potential to understand disease risk, detect disease early and enable preventative interventions.

Click Here to watch the videos from the Symposium.

Canary Foundation’s Ovarian Cancer Initiative: moving forward with matching specimen and imaging tissue in 3D

March 8, 2021

The Canary High Grade Serous Ovarian Cancer (HGSC) study is leveraging the expertise and resources of four institutions to study the microenvironmental factors that can lead fallopian tubes to develop this deadly type of ovarian cancer and thus provide a signal to alert for the presence of early disease. The Fred Hutchinson Cancer Research Center in Seattle, the University of Pennsylvania, the Van Andel Institute in Michigan, and the University of California San Francisco have built the infrastructure to share fallopian tube specimens, experimental and clinical data, and analytical teams.

The small pilot study goals are to ask whether it is possible to compare women carrying the BRCA mutations (who are at higher risk of developing ovarian cancer) compared to those who do not carry the mutation and determine whether it is possible to find a measurable difference in the microenvironment.

Based on their first results, the team is selecting a larger set of specimens, matched for clinical factors and BRCA mutation status, and will conduct RNA, DNA and methylome sequencing. The group is also comparing competing platforms for imaging the tissue expression in 3D so that differences along the length of the tube can be evaluated and tested for correlations with the genetic data.

The Canary Center is utilizing expertise to enhance COVID-19 vaccinations

COVID-19 is caused by a novel strain of coronavirus called SARS-CoV-2, which infects cells along the respiratory tract. Early on in the pandemic, Dr. Ramasamy Paulmurugan’s research group sought to explore a non-invasive and efficient vaccination strategy to raise the immune system to fight against COVID-19 at the initial site of infection: the nasopharyngeal region and the lungs.

The pulmonary immune system is considered a major immune organ in humans, containing the majority of T cells, which respond rapidly to infections in the respiratory tract. Hence, developing a vaccination approach for respiratory mucosal immune system can mount a strong immune response against the virus and raise the amount of resident memory B and T cells to provide a long-lasting neutralizing and cell mediated immunity to infectious agents.

With this promising scope in sight, Dr. Paul’s research group is exploring intranasal delivery of a multivalent mRNA vaccine, that effectively induced antibodies as early as two weeks after two doses of the DNA vaccine. This is expected to provide a long-term immunity to COVID-19.

Currently the team is expanding the study to multivalent mRNA vaccine for its wide spectrum antibody to encounter a range of mutant strains, which are dominating and contributing to second and third waves of infection around the world.

Canary’s International Collaboration – ACED

The International Alliance for Cancer Early Detection (ACED) joins researchers from the United States and the United Kingdom in a $70 million partnership. Founded in 2019, ACED is a partnership with the Canary Center at Stanford University, CRUK, the University of Cambridge, the Knight Cancer Institute at Oregon Health and Science University (OHSU), University College London and the University of Manchester. The following is one study chosen for it’s innovative approach to early detection:

Stratifying Risk for Early Detection in Hereditary Breast and Ovarian cancer
Project Award, led by: Marc Tischkowitz, University of Cambridge; Allison Kurian, Canary Center at Stanford for Cancer Early Detection; and Gareth Evans, University of Manchester. Stanford Team: Allison Kurian, Alice Fan, James Ford

CanRisk is a cancer risk assessment tool which combines genetic, lifestyle, clinical and imaging data to calculate an individual risk estimate for women with high-risk mutations in BRCA1 and BRCA2. The ability to provide personalized cancer risk estimates will identify women at particularly high risk. Currently, the ranges of cancer risk estimates for women with hereditary mutations in breast cancer genes are wide and not personalized, so all women are given the same figures. Creating a customized approach can solve this problem.

By implementing personalized risk estimates, early detection strategies can be tailored for the individual, therefore identifying those at the highest risk. Once feasibility is assessed, women undergoing predictive testing for BRCA1, BRCA2, PALB2, ATM or CHEK2 in US and UK genetics centers will be randomized to conventional vs personalized risk estimate based on genetic/lifestyle/hormonal modifiers.

Canary Foundation Welcomes Dr. Joseph DeSimone

November 22, 2020

Dr. Joseph DeSimone

We welcome Professor Joseph M. DeSimone, PhD. in the position of the Sanjiv Sam Gambhir Professor in Translational Medicine. We are fortunate to have such creative and capable leadership as our work together in cancer early detection continues.

From the Stanford Press Release: The Stanford Department of Radiology is proud to announce Professor Joseph M. DeSimone as the inaugural Sanjiv Sam Gambhir Professor in Translational Medicine. A shining example of achievement, Joe has been described as “an igniter of innovation”. He has received international recognition as a scientist, inventor, and entrepreneur, earning major accolades including the U.S. Presidential Green Chemistry Challenge Award, the 2017 Heinz Award, and the Lemelson-MIT Prize. He is one of only 25 individuals elected to all three U.S. National Academies—the National Academy of Sciences, Medicine, and Engineering. In 2016, President Obama presented him with the National Medal of Technology and Innovation, the highest honor in the U.S. for achievement and leadership in advancing technological progress. Read more here.

Joe and his lab have made significant scientific breakthroughs in science and medicine including next-generation approaches to cancer treatment and diagnosis, implantable drug delivery devices, green chemistry, and most recently in 3D printing technology for medical devices tailored to an individual patient’s needs. A dedicated educator and strong advocate for bringing a broader diversity of perspectives into research, he has mentored over 80 students through PhD completion at Univ. of North Carolina and North Carolina State Univ. (his former 30-year career), half of whom were women and members of underrepresented groups in STEM.

As an avid researcher and innovator, Joe has authored over 370 scientific publications with over 42,000 citations to his work, and is a named inventor on over 200 issued patents. Additionally, he brings a unique ability to transfer novel solutions from his lab to the world through the companies he co-founded.

Early Detection of Cancer Annual Conference – hosted by Cancer Research UK, OHSU Knight Cancer Institute and the Canary Center at Stanford brought together the brightest minds in cancer research with a record 600 registrants!

October 26, 2020

Highlights of the conference include:

• DON LISTWIN AWARD for Outstanding Contribution to Cancer Early Detection was awarded posthumously to Sanjiv Sam Gambhir, Canary Center Director, an internationally recognized pioneer in molecular imaging who dedicated his career to developing methods of early disease detection.
• Jon Emery (University of Melbourne) Cancer screening intensity should be matched to an individual’s risk of getting cancer. He described efforts to use genetic testing to help patients make informed decisions on colorectal cancer screening.
• Amelie Lutz (Stanford University) is developing an ultrasound guided molecular imaging method for detecting ovarian cancer using microbubbles that target tumor angiogenesis.  They’re focusing on whether the KDR labeled microbubbles actually detect the VEGFR2 expression in the tumor vasculature and whether the KDR bubbles can help to differentiate benign vs malignant (NIH grant work). Her talk highlighted how their team tackled the tricky part where the in vivo imaging has to be matched with the ex vivo histology, and how it required close communication between the imager, the surgeon and the pathologist. So far they have results from 7 patients, planning to go up to 50 (results matched in 6/7 cases).
• Stefano Avanzini (Stanford University) is using mathematical models to estimate the size tumors must reach to become detectable by tumor DNA circulating in blood.
• Parag Mallick (Stanford University) explained how tools such as saliency mapping are making it possible to understand how the machines reach their conclusions – building confidence and potentially revealing biological insights. He also showed examples of Artificial Intelligence tools for biomarker discovery that extract and create knowledge from massive, unstructured data sets.
• Cancer Research United Kingdom released an early detection road map, published in the Lancet (pdf): https://www.cancerresearchuk.org/sites/default/files/early_detection_diagnosis_of_cancer_roadmap.pdf
• KEYNOTE TALK • Dinah S. Singer (National Cancer Institute) began with a rundown of the NCI’s response to COVID-19 pandemic, from virus-focused research initiatives to the ways the agency is flexing to support grantees. She concluded with an overview of the cancer early detection programs the agency has underway, such as the Early Detection Research Network (now focusing on Artificial Intelligence and machine learning to integrate omic data to find biomarkers), and The Human Tumor Atlas Network (HTAN), a massive effort to map the complex ecosystems of cancer – and pave the way for advances in prevention, early detection and treatment.

Brief from The Early Detection of Cancer Conference  #EDx2020   –   recaps the entire conference, from their website: http://earlydetectionresearch.com    October 6-8, 2020

Our ovarian cancer team continues to build infrastructure for innovative pilot study and biobank.

October 7, 2020

The Ovarian team has used these past months to hone and polish the infrastructure for the High Grade Serous Ovarian Cancer Initiative and to ensure that high quality molecular data can be generated from the samples. This includes both the pilot project that focuses on changes in the micro-environment, and the retrospective study that looks back at tissue.

Focus of the project
Our focus is to define the role of the fallopian tube micro-environment in the development of high grade serous ovarian cancer (fallopian tube being the most common ovarian cancer), with the ultimate objective to find targets for prevention and markers of early disease onset for early detection.

Convening experts
In order to develop a robust and innovative research plan, we invited a multidisciplinary team of roughly 25 world class ovarian cancer researchers from across the US and Canada to an initial two day planning meeting in March 2019 in Los Gatos, California. The meeting was highly successful.  The number of promising ideas exceeded our available funding level.  Over the ensuing months the Executive Committee worked to refine and finalize our research proposal and also put in place the necessary infrastructure to conduct our studies.

What problem is the team trying to solve? Our overall plan includes a series of innovate pilot studies specifically designed to demonstrate the power of our team and generate preliminary data that can be leveraged to compete for large grants by the end of a two year period.   The research will be performed in two phases: first, a retrospective phase that involves analysis of previously collected, banked fallopian tube samples with associated clinical information, and second, a prospective study, that includes newly collected samples, each with the goal of identifying what changes in the molecular landscape signal cancer.

Our progress March – Summer 2020. During these past months, the team has finalized the infrastructure for the pilot program and has worked to ensure that the expected high quality molecular data from our samples can be achieved. The process for sample sharing has been completed. Additionally, reviews, discussions, and decisions have been held to work out a draft of the high-quality protocol necessary for all team members to follow. 6 potential sites have been identified. We are testing our data management processes. This includes a portal for sharing and annotating data among multiple investigators and analysts.  Canary Foundation has experience in this field.

Next steps: the in-person clinical aspect of the pilot will resume when each of the participating sites are reopened. When further steps in reopening allow, clinical sites will be responsible for providing patient samples and annotated clinical and pathologic data in a timely and cost-effective way. Each site includes a collaborative PI who has a robust system in place for conducting translational research studies, banking samples and linking clinical information.

Additionally, steps are being taken to identify and put in place a central project manager. An interim plan is in place utilizing resources at the University of Pennsylvania.

Organizational Structure
Clinical data and sample coordination center:  The University of Pennsylvania leader is Michael Feldman. We are working with the team at UPenn to write sample protocols and requirements and to finalize the overall collaboration agreement that will be signed by all institutions. The coordinating center will receive samples from clinical sites, perform quality control, and prepare and ship samples to molecular profiling sites. The center will also maintain the clinical database of participants linked to their sample information. The clinical data will be linked later to the molecular data for each of the samples and participants.

Clinical teams: when further steps in reopening allow, clinical sites will be responsible for providing patient samples and annotated clinical and pathologic data in a timely and cost-effective way.

Molecular profiling sites:  Molecular analyses will include bulk RNA and DNA sequencing, global methylome profiling, proteomics with spatial profiling, single cell analyses using the Nanostring DSP platforms.

Data management and analysis center:  We have multiple types of data that need to be securely stored and annotated. We are using a similar structure to that used by the large NIH-funded effort, TCGA.  Raw data will be hosted in the data center managed by Adam Olshen at UCSF.  We will run data analysis pipelines and upload processed data into a program that will function as a portal for sharing and annotating data among multiple investigators and analysts.  Canary Foundation has experience in this field.

Shaping bioinformatics. Our leadership and analysis team leaders are enthusiastic about working together using Synapse and the Sage engineers. The associated infrastructure and analysis plan from our bioinformaticians Adam Olshen (UCSF) and
Hui Shen (Van Andel) has been reviewed and approved by the group.

Checking our system.

• Testing of infrastructure and logistics with a small set of samples will include:
• Assessing technical issues
• Management of resources
• Rapid course correction procedures
• Generating first data set
• Send samples through the pipeline (10 BRCA mutation carriers)
• Check quality control measures on data set

Working as a team. Part of the strategy is to demonstrate our ability to work together and generate data so that we are able to apply for additional support from external agencies (e.g. government or foundations). The team is actively making connections to seek out the best funding opportunities as part of our future plan, and the breadth of expertise in the team and their ability to work well together go a long way in securing future funding.

Our prostate cancer team has big news from the Prostate Active Surveillance Study (PASS) – a new publication in JAMA Oncology!

Our prostate cancer team has more than a decade of experience working remotely from various institutions. During the time of the pandemic, the team has moved forward on important fronts.

Big News –PASS has a new publication in JAMA Oncology! A scientific paper was recently published in the premiere publication JAMA Oncology: The Journal of the American Medical Association. JAMA is a rigorously peer-reviewed medical journal. The principal investigator Matthew R. Cooperberg is on Canary’s Prostate Active Surveillance Study (PASS) team. Many familiar names from the team are seen on the study. The study shows an important way of determining risk assessment that can aid in deciding how often to monitor and other decisions.  To hear an interview with Dr. Cooperberg, click here:
https://edhub.ama-assn.org/jn-learning/audio-player/18536720

Tissue Microarray.  The team studies the progression of prostate cancer using high-through analysis of multiple cases. Work in this area during the pandemic has included the review of new proposals and project progress from partners, including ones from Austria and Canada. The work has included data analysis, correcting missing data, and arranging tissue shipment.

PASS Central Review. Decisions have been made on reviewing cases.

Meetings and communications. The prostate team has been disciplined in meeting remotely and communicating long distances since it’s formation in 2006. A group meeting was held in June and follow up ensued. Additionally, their annual November in-person meeting has been approved to move to a virtual format.

Enrolling men. PASS enrolls men to keep a steady level of patients as some men rotate out of the program, 2000 being the current number of enrollees. Enrollment is on hold due to the pandemic.

Other action of the Prostate Team include:

1. Reviewing new proposals for Canary TMA (pathology)
2. Progress on approved projects for Canary TMA (pathology) has been made with data having been submitted from a number of groups and a shipment of tissue samples having been coordinated to an international partner.
3. Concordance project for PASS central review (pathology), coordinated decision making on review of cases.
4. Papers: read and commented on meeting submissions and manuscripts in progress.
5. Administrative: we have held an all-team PASS and prostate pathology group meetings, distributed notes & action items. Plan approved to move November 20 meeting to virtual format.

The Canary Center at Stanford – A word from our researchers on safely reopening

September 16, 2020

Over the years, Canary Foundation has helped researchers develop successful ways of working together over distance, and we draw on that experience during these times.

A message on the Canary Center re-opening from:

Dr. Utkan Demirci, Co-Director, Canary Center at Stanford
Dr. Ryan Spitler, Deputy Director of the Precision Health and Integrated Diagnostics Center
Dr. Sharon Pitteri, Associate Professor, Canary Center at Stanford

We discover ways to move forward while staying safe. From the very early arrival of COVID-19, we have been able to successfully keep the Canary Center vibrant with virtual interactions and with safety in mind. We have implemented measures for social distancing, and staggered laboratory shifts as we follow the guidance on re-opening stages from the Radiology department and Stanford University. We are using our time out of the lab well.  Many researchers have taken this hard-to-find time to focus on data analysis, writing manuscripts, reading scientific literature, and developing new ideas for future projects. We also are exploring intersecting dimensions between cancer and COVID-19 related research. We have asked ourselves this question: how are we uniquely positioned to contribute to the pandemic crisis through the work we are doing in cancer early detection?

We look after each other. Everyone working in the Center has committed to the safety and well-being of every other Canary member. This is key. Each research group also has their own independent safety plan to ensure they are aware of their colleagues as well as their specific research needs. Collectively, we have been building up our research efforts in phases.

We will continue to push forward to detect cancer before it strikes and support COVID-19 related efforts. Take our Smart Toilet system. The Smart Toilet system is a wave-of-the-near-future method of collecting important changes in biodata to serve personalized medicine.  We have been able to modify our Smart Toilet system originally designed for early cancer detection to also be used as a screening tool to detect COVID-19. This approach enhances longitudinal testing and serves to detect very small, early changes. Unnecessary exposure is also limited for the patient and the health care provider who normally must come in close proximity for a nasal swab that often triggers a cough or sneeze.

Human health is our passion and one that burns strongly no matter what challenges we face.

To better envision the opening of the Canary Center, please enjoy this brief video.