Research

Dr. Karen Abbott’s research is currently focused on three main areas: translational therapeutic development, studies on the role of Notch glycosylation in ovarian cancer progression, and technology development for the study of glycosylphosphatidylinositol-anchored proteins.

  • Project 1: Translational Therapeutic Development

    We have isolated a human scFv antibody that binds tumor-specific bisecting N-linked glycans present on ovarian cancer cells.  Our goals with this project are to develop novel therapeutics using this antibody.  We are developing PROTAC therapeutics that can recruit ubiquitin ligases to the antibody target glycoproteins and degrade them.  We are also developing chimeric antigen T cell therapeutics using the scFv antibody for tumor targeting.

  • Project 2: Studies on the role of Notch glycosylation in ovarian cancer

    The Notch receptors and the glycosyltransferases that glycosylate Notch are both amplified in ovarian cancer.  We have discovered that the Notch pathway is regulating the cancer stem cell populations in ovarian cancer. The goals of this project are to determine how the N-linked bisecting glycans and O-fucose glycan modifications on Notch impact ovarian cancer growth and progression.  We are using multiple approaches in this study including CRISPR/Cas9 knockout of key glycosyltransferases, in vivo xenograft studies to determine the effects on tumor growth, and mass spectrometry identification of glycan structures on Notch from clinical samples.

  • Project 3: Technology development for the study of GPI anchored proteins

    The GPI anchor is a lipid and glycan structure that is added to certain proteins to anchor them to the membrane. This type of membrane linkage is on the external side of the plasma membrane in lipid rafts. The presence of GPI-anchored proteins influences cell signaling and controls many vital cell functions.  GPI anchored proteins are increased in human cancers making them potential biomarkers. The goal of this project is to create a GPI peptide array that can be used to identify proteins that interact with GPI anchored proteins. This knowledge can lead to new potential diagnostic and therapeutic targets for cancer. We are also optimizing the mass spectrometry characterization of the GPI anchors using multiple forms of fragmentation and ionization.