Accelerating clinical and translational research for biomarker discovery through advanced, standardized cell isolation methodologies
Recorded On: 02/05/2018
Specimens are not meant to live in a freezer. Their sole purpose in life is to produce data. Biorepositories are critical to accelerating clinical and translational research technologies and discoveries. Human subject research depends on the availability of standardized biorepository methods for collection, storage, processing, and distribution of biological specimens alongside associated patient metadata. Stanford Medicine’s growth across the Bay Area has created an opportunity for us to connect participants to bench-side research in ways never before possible. Our biobank has an emphasis on more advanced sample processing geared at downstream, functional analysis using viable cell suspensions. Work is often performed in tandem with specialized assay groups, such as the Human Immune Monitoring Center (directed by Dr. Holden Maecker) to leverage cutting-edge technologies such as CyTOF, single-cell RNA sequencing, flow cytometry, and immunoassay. Many of these assays require specimen types from humans that have been processed using very specific techniques and methodologies to prevent the introduction of artifacts. In particular, the standardization of the procedures for cell isolation is critical to the success of the translational research; by increasing throughput and minimizing ‘hands-on’ time, applications for biomarker discovery have a chance to be accelerated and reproduced.
At Stanford Medicine, the lab of Dr. Irving Weissman has coordinated the build out of a unique biorepository dedicated to collection and advanced, standardized processing of tissue and tumors into viable single-cell suspensions. Over the course of the last two years, tumors with match normal tissue have been collected alongside archives of clinical, pathology and surgical notes. In November 2016, Sydney Gordon, a graduate student in Weismann’s lab, discovered the novel increased expression of PD-1 on tumor macrophages in colon cancer of mouse models. Sydney was hoping to translate her findings into humans and did so by taking advantage of Stanford’s biorepository. Within a matter of two months, Sydney was able to repeat her discovery on human samples that had been preserved for functional analysis. She validated her findings of increased PD-1 expression on human colon cancer tumors, opening the door to multiple discussions around new drug therapeutics in cancer immunotherapy. Key to her success was the standardization and care taken to procure and process the solid tissues into single-cell suspensions with minimal impact to the cell surface antigens and cryopreserve the cells viably. Automating parts of this pipeline presents an opportunity to greatly improve the throughput, while also standardizing the methodology away from technician variability.
I began my research at Stanford in 2003 and now oversee harmonization and alignment efforts for biobanking infrastructure, alongside directing the largest research focused, ambulatory care unit at Stanford, the Clinical and Translational Research Unit (CTRU). Both efforts are part of Spectrum’s vision to provide innovative and compliant resources for research services to the research community both locally and globally. Notably, I’ve led and established the biorepository and associated data infrastructure for multiple large-scale biobanks, including those associated with Spectrum, Parker Institute for Cancer Immunotherapy, Stem Cell Institute, Institute for Immunology/Transplantation/Infection, Blood and Bone Marrow Transplant Biobank, Google Baseline, and many more.