SEP 07, 2017 9:00 AM PDT

WEBINAR: Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity

Sponsored by: Essen BioScience
Speaker
  • Instructor, Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, USA
    Biography
      I earned my Ph.D. degree in the Department of Pharmacology at the University of Medicine & Dentistry of New Jersey (UMDNJ) in 2007. Following graduation, I joined Dr. Mien-Chie Hung's lab at U.T. M.D. Anderson Cancer Center as a postdoctoral fellow. I was later appointed to an instructor position at MD Anderson. My research lies in understanding the regulatory mechanisms of PD-L1 for the identification of novel therapeutic targets, enhancing the efficacy and safety of immunotherapy. In addition, I have tremendous interest in studying breast cancer metastasis mechanisms, aiming to develop novel therapeutic strategies. Another focus of my research is on dissecting the PARP inhibitor resistance mechanism in triple negative breast cancer. I will use my research expertise in these areas as a Co-Investigator on Project 2 of the Breast SPORE.

    Abstract

    DATE: September 7, 2017
    TIME: 9:00AM PT, 12:00PM ET

    The success of immune checkpoint blockade adds a new therapeutic category to the cancer therapy repertoire. Despite efforts made on cancer cell and immune cell interaction, how cancer cells initiate immune escape is less understood. Here we reveal PD-L1’s immunosuppression activity is stringently modulated by the spatial restraints between ubiquitination and N-linked glycosylation. We identified GSK3beta as a novel PD-L1 interacting protein capable of inducing phosphorylation dependent proteasome degradation. The essence of PD-L1 N192, N200 and N219 glycosylation suggests it antagonizes GSK3beta binding. In this regard, only non-glycosylated PD-L1 forms a complex with GSK3beta and beta-TrCP. More importantly, activation of GSK3beta-mediated PD-L1 degradation by TKI can reduce membrane PD-L1 expression and thereby enhance anti-tumor immunity. To test T cell-mediated cancer cell killing in vitro, we employed a time lapse microscopy, IncuCyte, to monitor RFP-tagged BT549 cells and activated PBMC interaction over a five day period. Massive cancer cell death was observed in glycosylation deficient cancer cells, suggesting glycosylation of PD-L1 is required for its immunosuppression. Together, our results link ubiquitination and glycosylation pathways with stringent regulation of PD-L1, proposing a new therapeutic strategy to enhance cancer immune therapy efficacy.

    Learning Objectives:

    • Molecular mechanism of PD-L1 regulation in cancer cells
    • Immunosuppressive nature of triple negative breast cancer 
    • Using in vitro co-culture system to analyze T cell-mediated cancer cell killing effect

     


    Show Resources
    You May Also Like
    MAY 11, 2021 10:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    C.E. CREDITS
    MAY 11, 2021 10:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    Date: May 11, 2021 Time: 10:00zm PDT Your samples are some of the most valuable assets in the laboratory. After spending countless hours on extraction and preparation, your conclusions could...
    JUN 09, 2021 7:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    C.E. CREDITS
    JUN 09, 2021 7:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    Date: June 9, 2021 Time: 09 June 2021, 7am PDT, 10am EDT, 4pm CEST cells with dramatic implications on the validity of past cell culture related research. The fact that at least 509 cell lin...
    DEC 02, 2020 8:00 AM PST
    C.E. CREDITS
    DEC 02, 2020 8:00 AM PST
    DATE: December 2nd, 2020 TIME: 08:00am PDT, 11:00pm EDT Bioreactors and shakers are used to cultivate microorganisms, plant, insect, and mammalian cells in different volumes. Upscaling of pr...
    NOV 18, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 18, 2020 8:00 AM PST
    DATE: November 18, 2020 TIME: 08:00am PDT We develop and implement technologies to solve some of the major bottlenecks in biomedical research. In particular, we establish new imaging approac...
    APR 21, 2021 10:00 AM PDT
    C.E. CREDITS
    APR 21, 2021 10:00 AM PDT
    Date: April 21, 2021 Time: 10:00am (PDT), 1:00pm (EDT) Serological testing for SARS-CoV-2 has been steadily adopted into clinical practice over the course of this pandemic. In this webinar,...
    NOV 16, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 16, 2020 8:00 AM PST
    Date: November 16, 2020 Time: 8:00am (PST), 11:00am (EST) CRISPR screening has become the prime discovery tool in modern biomedical research and drug discovery. At the same time, most screen...
    SEP 07, 2017 9:00 AM PDT

    WEBINAR: Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity

    Sponsored by: Essen BioScience

    Specialty

    Cancer Research

    Immunology

    Molecular Biology

    Cell Biology

    Biotechnology

    Cancer Therapeutics

    Biomarkers

    Biochemistry

    Cancer Diagnostics

    Cell Culture

    Molecular Diagnostics

    Clinical Diagnostics

    Gene Expression

    Laboratory Testing

    Genetics

    Geography

    North America64%

    Europe15%

    Asia13%

    South America4%

    Africa2%

    Registration Source

    Website Visitors100%

    Job Title

    Research Scientist18%

    Student17%

    Educator/Faculty13%

    Scientist12%

    Post Doc10%

    Executive8%

    Medical Laboratory Technician7%

    Medical Doctor/Specialist4%

    Lab Management4%

    Facility/Department Manager4%

    Clinical Laboratory Scientist3%

    Organization

    Academic Institution14%

    Biotech Company6%

    Clinical Laboratory4%

    Hospital4%

    Research Institute3%

    Medical School3%

    Government3%

    Medical Center2%

    Pharmaceutical Company1%

    Consultant1%

    Life Science Company1%

    Industrial Company1%

    Independent Laboratories1%

    Ambulatory Care1%

    Other4%


    Show Resources
    Loading Comments...
    Show Resources
    Attendees
    • See more