Research

Research in the Broderick Laboratory

My research program focuses understanding of genetic immunodysregulatory disorders through the methodical investigation of the molecular basis of underlying disease pathology. Using the patient-driven questions, we have focused on rare, immunologic diseases from immunodeficiency to Autoinflammation. Through discovery of the genetic and physiologic mechanisms behind these defined syndromes, we aim to use this knowledge to design diagnostic tests and identify new life-saving therapies. We believe that the discovery of genes responsible for rare immunologic disorders can lead to a better understanding of fundamental immune pathways in human health and disease.

PFAPA syndrome
During my training at UCSD, I developed an interest in patients with autoinflammatory syndromes, and the role of the inflammasome in the pathophysiology of these disorders. At the Recurrent Fever clinic at Rady Children’s Hospital San Diego, we have developed a niche for patients with autoinflammatory diseases, including CAPS, TRAPS and FMF. We have further applied these approaches to a more recently described autoinflammatory disorder, Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome. This systemic inflammatory disorder of childhood is characterized by recurrent attacks of fever, sore throat, mouth sores, swollen lymph nodes, and increased white blood cell counts, driven by IL-1. Current studies are investigating the genetics and mechanisms underlying this recurrent fever disorder.

Primary Immunodeficiency
We also study the molecular pathophysiology of the opposite end of the immune spectrum: immunodeficiency, with the identification of novel gene defects in complement leading to acute hemorrhagic leukoencephalitis, a rare disorder with high (>90%) mortality. Using genetic and in vitro models, we identified a new role for IL-1 in this disorder, and we successfully used IL-1 blockade in the clinic, leading to survival of our patients.