PHIND Seminar August
Mehmet Ozgun
“Extracellular Vesicles for Broad Applications in Medicine and Cancer”
About Mehmet O. Ozen, PhD
Dr. Ozen is a Postdoctoral Research Fellow at Canary Center for Cancer Early Detection / Radiology Department at Stanford University. He works with Prof. Utkan Demirci on simple solutions for complex problems in medicine, combining microfluidics and bioengineering principles. He received his BS and PhD in Bioengineering from Ege University.
Abstract
Extracellular vesicles (EVs) are lipid bi-layered nanoparticles shed from the cells that carry RNA, DNA, transmembrane and cytosolic proteins. The variety in EV size, cargo and origin attracted researchers to decipher the mechanisms that have been involved in packaging, secretion, uptake and roles of EVs on cells in vivo and in vitro, lightening the path for biomarker studies for diagnosis, prognosis, therapy and therapy monitoring. They are one of the many means that cells use to communicate with neighboring and distant cells and tissues. With improvements in next-generation sequencing technologies and increased resolution of mass spectrometry for proteomic analysis, EVs have been shown to take role in angiogenesis, epithelial-to-mesenchymal transition, stemness in cancer, malignancy, metastasis and drug resistance.
Although exosomes show unprecedented promising advantages over other biotargets in the circulation for clinical use, a major challenge rapidly emerging in the field of EV utilization for clinical and non-clinical applications is the absence of reproducible, inexpensive and robust tools for efficient sorting and isolation of EV populations at a high yield. The field lacks a clear consensus over an optimum approach or a tool for isolation of EVs avoiding contamination with many other proteins and such other biostructures and reproducible procedures for downstream analysis of EV cargo and content. Existing approaches for EV isolation include a variety of methods. Additionally, methods for the exosome-derived analyte isolation, library preparation for sequencing, and downstream analysis including genomic, proteomic and metabolic analysis are highly varied. Hence, there is a need for well-developed experimental tools, interlaboratory evaluations and in-depth descriptions of experimental steps and designs to ensure reliable, robust and reproducible experiments and tools.
In this talk, we will describe a new technique, i.e., Exosome Total Isolation Chip (ExoTIC), that is developed in our lab to isolate EVs and EV subpopulations from a variety of sample types including plasma and culture media. We will present further downstream genomic and proteomic analysis of these EVs focusing on applications in cancer and cardiovascular disorders.
PHIND Seminar Series October: ‘Progression of Clonal Hematopoiesis of Indeterminate Potential to Acute Myeloid Leukemia’
Ravi Majeti, MD, Ph.D.
Professor of Medicine
Chief, Division of Hematology
Institute for Stem Cell Biology and Regenerative Medicine
Stanford University
Munzer Auditorium (B060), Beckman Center
11:00am-12:00pm – Seminar and Discussion
12:00pm-12:15pm – Reception (light refreshments provided)
RSVP Here: https://www.onlineregistrationcenter.com/register/222/page1.asp?m=298&c=39
ABSTRACT: Myeloid malignancies are cancers of the blood lineage including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML) with more than 40,000 new diagnoses annually in the United States. These diseases cause significant morbidity and mortality due to associated bone marrow failure leading to anemia, bleeding, and infections, and are currently treated with targeted therapies, chemotherapy, and allogeneic bone marrow transplantation. Next generation DNA sequencing has determined the spectrum of mutations associated with these cancers and has found that most cases are associated with multiple mutations that cooperate to cause disease. In our prior studies, we determined that these mutations are serially acquired in clones of self-renewing pre-cancerous/pre-leukemic blood stem cells. Separate studies analyzed blood sequencing data from large cohorts of individuals without disease and found these pre-leukemic mutations occur in the general population with increasing frequency and incidence with age. As only a minor subset of these individuals eventually progressed to develop myeloid malignancy, this entity was termed clonal hematopoiesis of indeterminate potential (CHIP). One major issue with implications for the transition from health to disease is to understand what factors influence the progression from CHIP to myeloid malignancy. In order to investigate this question, we have developed models for CHIP/pre-leukemia through the CRISPR-mediated engineering of normal human blood stem and progenitor cells. By introducing mutations in the TET2 and ASXL1 genes that are commonly mutated in CHIP, we have established models for the cell intrinsic processes of progression to myeloid malignancy and are now poised to examine cell extrinsic processes that can affect such progression. Establishing these models is key to investigating measures to eventually prevent development of myeloid malignancy.
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
PHIND Seminar Series November: ‘ What You Always Wanted to Know about Economics, Payer Coverage, and Big Data for Precision Health – But Were Afraid to Ask’
Kathryn Phillips, Ph.D.
Professor of Health Economics
Founding Director of the UCSF Center for Translational and Policy Research on Personalized Medicine (TRANSPERS)
Department of Clinical Pharmacy
UCSF
Li Ka Shing Center, LK101
11:00am-12:00pm – Seminar and Discussion
12:00pm-12:15pm – Reception (light refreshments provided)
RSVP Here: https://www.onlineregistrationcenter.com/KathrynPhillips
ABSTRACT: Precision Health offers an opportunity to achieve “high value care” through innovative approaches. However, in order to fulfill this objective, we must demonstrate its economic value, someone must be willing to pay the costs, and there has to be data available to provide the needed evidence. In this talk, I will draw on my research over the past decade examining (1) how to measure the value of complex technologies such as Precision Health, (2) what payers cover and how they decide to provide coverage, and (3) how Big Data can be leveraged. I will also describe “lessons learned” about successful adoption from working with dozens of start-ups, VCs, and biotech companies. The talk will illustrate these issues using the case study of “liquid biopsy” – a potentially transformative technology that illustrates both the opportunities and challenges for Precision Health.
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.
PHIND Seminar Series: “Prediction of Future Lymphoma Development Based on DNA Methylation Profiles from Peripheral Blood”
Almudena Espin Perez, PhD
Postdoctoral Research Fellow
Biomedical Informatics
Stanford University
Beckman Center, Munzer Auditorium (B060)
12:00pm – 1:00pm Seminar & Discussion
1:00pm – 1:15pm Reception & Light Refreshments
RSVP here: https://www.onlineregistrationcenter.com/APerez
ABSTRACT
Subjects with Non-Hodgkin Lymphoma (NHL) have abnormal lymphocytes that multiply and accumulate to form tumors in the lymph nodes and other organs. Currently, there are no predictive models with high performance that can predict the risk of developing NHL.
We present a computational framework that accurately predicts future (up to 16 years) NHL from a signature based on DNA methylation profiles of peripheral blood samples. We studied differences in specific DNA methylation levels from blood samples between future NHL group and the control group (470 samples) from two prospective cohorts. We developed a predictive model using advanced artificial intelligence methods for NHL diagnosis based on a set of key CpG sites. The validation tests showed that our signature 1) predicts mainly “control” in an independent population of 656 healthy subjects, 2) predicts “future case” with extremely accurate performance in tissue samples from four independent NHL cohorts (662, 29, 31 and 29 subjects), with one of the cohorts (662 subjects) corresponding to children with B-cell lymphoma, 3) predicts mostly healthy in a cohort of children with 74 children in remission, 4) works for both HIV positive subjects and HIV negative subjects, 5) yields almost perfect predictions regardless of the NHL subtype, and 6) is 84% accurate at predicting T-cell lymphoma in children, despite its derivation in B-cell lymphoma in adults.
ABOUT
Almudena Espin Perez’s interests include developing algorithms and novel computational methods for early cancer detection. High-throughput technologies in the field of molecular biology are generating huge amounts of biological data and transforming the scientific landscape. A major focus of her research is on building computational methods to 1) study genomics and epigenetic data 2) integrate genomics and imaging data at single-cell level resolution and 3) leverage existing large-scale transcriptomic datasets to address relevant biological questions by developing computational deconvolution tools to infer the abundance of different cell types from mixed cell populations. Dr. Perez aims to improve the understanding of the molecular mechanisms behind cancer development, which could potentially lead to biomarker discovery and improve early detection, treatment strategies and decision-making.
Hosted by: Sanjiv Sam Gambhir, M.D., Ph.D.
Sponsored by the PHIND Center and the Department of Radiology
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!
PHIND Seminar Series: “A Stroke Monitoring and Alert System for a Future Without Late Presentation”
Orestis Vardoulis, Ph.D.
Postdoctoral Research Fellow
Pediatric Surgery
Stanford University
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