Veterinary ImmunotherapyChimeric antigen receptor (CAR) therapy combines the specificity of an antibody-derived single-chain variable fragment with potent signaling domains to direct immune cells against disease targets like infected cells. This approach has shown remarkable success in human hematologic cancers, but has not yet been developed for cats. Challenges for implementation in veterinary medicine include high cost and the need for autologous immune cells.
As a first step toward feline CAR therapies, our lab established the reagents and methods to generate feline CAR T cells. We also produced a prototype CAR targeting feline coronavirus spike protein. Innate Immune Signaling
Nearly every disease has an underlying component of inflammation, or involves tissue damage and repair. Macrophages are an amazingly adaptable innate immune cell that detects infection and damage through innate immune receptors such as Toll-like receptors (TLRs). To boost effectiveness of vaccines and immunotherapies, or to dampen chronic inflammation and autoimmunity, we must understand the molecular mechanisms underlying these responses.
The overall theme of our research is to understand how innate immune receptors are regulated. This is important for human health because although most innate immune receptors detect unique molecular structures present on microbes and not in the host, a few detect highly conserved structures such as nucleic acids (DNA and RNA). Transmembrane receptors that detect DNA and RNA belong to a family of innate immune receptors called Toll-like receptors (TLRs). |
The research in the lab addresses three broad questions:
1. What are the intracellular regulatory mechanisms that govern activity of innate immune receptors? 2. What are the contributions of TLRs and macrophages in broader applications such as vaccines, immune responses to infection, and other immune-mediated diseases? 3. How do extracellular cues modulate macrophage TLR signaling and inflammation? |