Three Current Areas of Research
Understanding How Checkpoints, Including Exosomes, Influence the Anti-Tumor Immune Response: Following our discovery that exosomes can suppress the immune response through the presentation of the checkpoint protein PD-L1, we have become broadly interested in how exosomes modulate immunity in the context of cancer. We are evaluating a novel inhibitor of exosome release as both a therapeutic approach and a tool to better understand exosome roles in vivo. Additionally, we are investigating other checkpoint proteins found on exosomes, including PVRL2, an understudied checkpoint that we recently demonstrated to have an even greater impact than PD-L1 in regulating the anti-tumor immune response. Our current efforts focus on dissecting the mechanisms of PVRL2, including its upregulation on tumors and its interactions with receptors on immune cells. We are also developing therapeutics targeting PVRL2.
Developing Pluripotent Stem Cell-Derived Dendritic Cells as Cell Therapies for Cancer and Autoimmune Diseases: Building on many years of studying pluripotent stem cells, we are now exploring the potential of combining genetic engineering of these cells with their differentiation into dendritic cells as innovative cell therapies for both cancer and autoimmune diseases. In both cases, we utilize universal pluripotent stem cells, which lack their own MHC class I and II molecules, rendering them invisible to allogeneic immune cells. For cancer therapy, we load these cells with MHC-peptides derived from tumor cells to create a cancer vaccine. For autoimmune diseases, we present patient-specific, autoimmune-inducing MHC-peptide complexes in the context of tolerogenic dendritic cells to inhibit immune cells that target self-antigens.
Studying the Regulation of Cell Fate in Extraembryonic Tissues of Human Reproduction: In collaboration with the Fisher Lab, we are investigating the mechanisms underlying the distinct fate decisions made by trophoblasts in the placenta versus the fetal membranes, which result in their differing morphologies and functions. This research includes examining these mechanisms in the context of pregnancy-associated diseases such as preeclampsia and premature rupture of membranes. We are also exploring how maternal health influences these cell fate decisions.