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.
Primary Immunodeficiency
Our work focuses on the molecular mechanisms and clinical impacts of inborn errors of immunity We recently described novel gene defects in a complement inhibitory protein (Factor I) as a predisposing factor 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 successfully used IL-1 blockade in the clinic as a life-saving therapy. Most recently, we published the genetic basis of Hoffman syndrome, a B cell specific immunodeficiency with dysmorphic features, due to mutations in the essential gene topoisomerase IIbeta. Our work defined an entirely new class of B cell immunodeficiency and the first Mendelian disease due to mutations in a topoisomerase. Ongoing studies are investigating the mechanisms underlying the role of TOP2B in hematopoietic cell development.
Autoinflammation
At the Recurrent Fever Disorders 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. Current studies are investigating the genetics and mechanisms underlying PFAPA syndrome and other undefined recurrent fever disorders.
Find a current list of the Broderick lab's publications on PubMed