Immune Tolerance in the Ovary & Uterus
Our lab investigates how specialized T cells preserve immune balance within reproductive tissues. In particular, we study conventional double-negative T cells (cDNTs), a rare subset that arises from CD8⁺ T cells and acts as a local guardian of tolerance. In the ovary and uterus, cDNTs prevent immune overactivation that could otherwise damage developing follicles or disrupt pregnancy. By mapping how these cells interact with other immune and stromal cells, we are uncovering the molecular cues that allow the immune system to recognize reproductive tissues as “self.” This work sheds light on how fertility is sustained through a delicate partnership between immunity and tissue biology.
Autoimmune Ovarian Failure
When immune tolerance fails, the same T cells that normally protect the ovary can turn destructive. We explore how this breakdown occurs in autoimmune ovarian failure (AOF), a poorly understood cause of infertility. Using mouse models and patient-linked datasets, we study how cytotoxic CD8⁺ T cells escape regulation and how loss of cDNTs contributes to ovarian damage. Our aim is to define early immune signatures of AOF and test strategies—such as adoptive transfer of tolerance-inducing T cells—that could restore immune balance and fertility. These findings could pave the way for immune-based therapies for infertility that go beyond hormonal treatment.
Ovarian Tumor Immunotherapy
Ovarian tumors exploit the same tolerance pathways that normally protect reproductive tissues. We are translating our discoveries in immune regulation into therapeutic design, re-engineering T cells to target ovarian cancer while minimizing autoimmune risk. This includes engineering CD8⁺ T cells and cDNT-derived cells with modified receptors, signaling circuits, or tethered cytokines to overcome tumor immune evasion. Our goal is to create safer, tissue-aware immunotherapies that harness the precision of tolerance biology to destroy tumors without harming fertility or surrounding tissue integrity.
Ovarian Computational Modeling
In collaboration with computational scientists and engineers, we are building an AI-based virtual ovary that integrates experimental and spatial data to simulate immune–tissue interactions. This platform will allow us to test hypotheses about tolerance and inflammation in silico before moving to animal or organoid models. By combining imaging, transcriptomics, and modeling, we aim to predict how immune cell networks respond to disruption—whether by autoimmunity, infection, or cancer. The long-term vision is a digital twin of the ovary that can guide precision therapies and diagnostic biomarker discovery.
