Dr. Hoffman’s main research interests are genetics and inflammation. The laboratory uses a combination of positional cloning of human disease genes and mouse transgenic technology to identify the function of disease genes. Previous and ongoing research concerns the autoinflammatory disorders -- a group of inflammatory diseases associated with unregulated inflammation in the absence of infection or autoimmunity. His work has focused on the study of one of these diseases, familial cold autoinflammatory syndrome, an inherited condition characterized by recurrent episodes of rash, fever, and joint pain following exposure to cold. Using positional cloning, Dr. Hoffman's lab identified the NLRP3 (CIAS1) gene that is responsible for this disease and codes for the protein cryopyrin (NALP3). Cryopyrin is a member of a family of innate immune proteins that are involved in the regulation of inflammation. Cryopyrin is involved in the activation of caspase 1, which leads to the release of interleukin-1. These studies have also led to the discovery of novel treatments for autoinflammatory disorders with implications for more common inflammatory diseases. Recently, Dr. Hoffman’s lab has identified a gene responsible for a rare inherited diarrheal disease and the lab is working on the developmental mechanisms underlying this life threatening disease.