To define the fundamental mechanisms of innate immunity and inflammatory responses to prevent, treat, and cure inflammatory and infectious diseases and cancer.
Innate immunity is the first line of defense against pathogens and sterile insults within the body, and the resulting inflammation forms the initial response to infection and injury. Genetic mutations in innate immunity affect the development of infectious, inflammatory, and autoimmune diseases, as well as cancers.
At the core of innate immunity and inflammation research is the investigation of pathogen- and damage-associated molecular pattern sensing mechanisms and the elucidation of downstream signaling cascades. This molecular machinery is central to preventing infectious diseases, and failure to regulate innate and inflammatory responses leads to inflammatory, autoimmune, neurodegenerative, and metabolic diseases and cancers. Therefore, understanding innate immune pathways is central to advancing therapeutic targeting across the disease spectrum.
Infection with herpes simplex virus 1 (HSV1) induces innate immune activation to drive the formation of the AIM2-PANoptosome. This multi-protein complex leads to innate immune-mediated cell death, a key mechanism for host defense against this virus. The AIM2-PANoptosome contains many innate immune sensing and cell death molecules. A cell stained for the key PANoptosome molecules caspase-8 (green), ASC (blue), and RIPK3 (red) is shown here.
Using the most advanced methods of molecular, cellular, chemical, and structural biology as well as genetics and immunology, the CoE-III will perform mechanistic studies to define this biological system. Through its efforts, the Center will support and progress the broader mission of St. Jude to advance cures, and means of prevention, for pediatric catastrophic diseases through research and treatment.
The CoE-III will focus on three primary research areas:
Infection with influenza A virus (IAV) induces innate immune activation to drive the formation of the ZBP1-PANoptosome. This multi-protein complex leads to innate immune-mediated cell death, a key mechanism for host defense against this virus. The ZBP1-PANoptosome contains many innate immune sensing and cell death molecules. A cell stained for the key PANoptosome molecules caspase-8 (green), ASC (blue), and RIPK3 (red) is shown here.
The St. Jude Children's Research Hospital research community fosters a highly interactive environment with plentiful collaborative opportunities across our basic research and clinical departments and access to state-of-the-art High Performance Computing (HPC) facilities and outstanding Shared Resources and Core Facilities managed by highly engaged Ph.D. level scientists. The $412M Advanced Research Center, opened in 2021, doubles the campus’s research space and adds support for an additional 1,000 employees. Clinically, St. Jude is consistently ranked Top 10 in the U.S. in Pediatric Cancer and is the only NCI-designated Comprehensive Cancer Center devoted solely to children, and hosts the Pediatric Cancer Genome Project. St. Jude’s commitment to ensuring no child dies in the dawn of life extends across the disease spectrum, and basic and clinical researchers work together every day to advance this mission.