Single Cell Functional Proteomics: Small Devices for Big Impact

Departments: Biomedical Engineering
Time: Tuesday, October 11, 2016 - 4:00pm - 5:00pm
Type: Seminar Series
Presenter: Rong Fan; Associate Professor of Biomedical Engineering, Yale University
Room/Office: Room 112
Location:
10 Amistad Street
New Haven, CT 06511
United States
See map: Google Maps

Department of Biomedical Engineering Seminar Series

"Single Cell Functional Proteomics: Small Devices for Big Impact" 
Rong Fan, Ph.D. 
Associate Professor of Biomedical Engineering 
Yale University

Abstract: Despite recent advances in single-cell genomic, transcriptional and mass cytometric profiling, it remains a challenge to collect highly multiplexed measurements of proteins produced from single cells for comprehensive analysis of immune functional states. Our laboratory developed a microdevice technology that simultaneously measures up to 42 immune effector function proteins secreted from single cells, representing the highest multiplexing recorded to date for a single-cell secretion assay. Applying this technology to profiling phenotypically identical macrophage cells reveals previously unobserved deep functional heterogeneity and varying levels of activation states. A subpopulation that can co-produce multiple effector proteins, called polyfunctional cells, are the "super warriors" dictating overall quality and durability of protective immune defense against pathogens. It was also applied to evaluating chimeric antigen-specific T cells (CAR-T) manufactured for clinical trials. These cells show profound polyfunctionality with a dominant profile of anti-tumor effector response at a single-cell level from a cohort of human donors and acute lymphoblastic leukemia patients, albeit mixed with a range of other functions such as stimulatory, immunosuppressive/regulatory, and immunotoxic/proinflammatory activities, yielding a landscape of immune effector response in CD19 CAR T cells to antigen-specific challenge. Intrigued by the role of polyfunctional cells in immune defense, we hypothesized that there exists a polyfunctional population in immune-mediated diseases but their role is linked to their ability in driving pathogenesis. We examined the production of a panel of cytokines in single hematopoietic cells from human myeloproliferative diseases (MPD) and observed an increased frequency of polyfunctional cytokine-secreting cells in MPD. We also investigated CD4+ follicular helper T (Tfh) cells in systemic lupus erythematosus (SLE) and found the polyfunctional Tfh cell population is expanded substantially in disease. Correlating effector functions to transcriptomic profiles measured on single Tfh cells suggests that these cells may directly contribute to autoimmunity and tissue damage. All these results underscore the complexity of phenotypically similar cell repertoire at the functional level in both protective immune defense and pathological conditions. Our microdevice technology permits a full-spectrum dissection of immune functional states and represents a truly enabling tool for immune profiling with applications to infectious diseases, cancer immunotherapy, hematologic malignancies, and autoimmune diseases.

When: Tuesday, October 11th, 2016 
Place: Amistad Conference Room 112 
Time: 4:00PM