Personal Statement

Moshe Arditi, MD, is the executive vice chair of the Department of Pediatrics for Research and the director of the Pediatric Infectious Diseases and Immunology Division at Cedars-Sinai. He is also director of the Infectious and Immunological Diseases Research Center in the Department of the Biomedical Sciences and a member of the Cedars-Sinai Smidt Heart Institute. Arditi is the program director of the Cedars-Sinai Immunobiology T32 training grant. He and his team have been among the leaders at Cedars-Sinai to promote the concept of "team science," with five principal investigators in his group focused on translating basic science advances to patients.

The Arditi Laboratory has received National Institutes of Health (NIH) funding continuously for the past 24 years. The broad focus of the group is on innate immunity and host-pathogen interactions as they relate to acute and chronic inflammatory diseases.

More specifically, the Arditi group investigates the innate and adaptive immune mechanisms that contribute to atherosclerosis, including the role of mitochondrial oxidative DNA damage, activation of the NLRP3 inflammasome and the IL-1beta pathway. Researchers in the Arditi Lab are performing translational research in human inflammatory disease models in which excess IL-1 signaling plays a key pathologic role. The team seeks to discover novel drugs to treat these diseases.

The Arditi Lab also investigates the mechanisms underlying the significantly increased risk of atherosclerotic cardiac disease in patients with autoimmune diseases, such as systemic lupus erythematosus, and is pursuing the mechanisms for gender differences in inflammatory disease, such as atherosclerosis, as well as responses to therapy that may be gender-dependent.

A major research focus of Arditi and his team is the discovery of the immunopathologic mechanisms that drive the development of cardiovascular lesions in Kawasaki disease vasculitis. The group uses a well-established and accepted experimental mouse model of Kawasaki disease vasculitis that recapitulates the coronary arteritis, abdominal aorta dilation, aneurysms and myocarditis observed in human patients. Arditi’s seminal findings using this experimental mouse model demonstrated the key role of IL-1 beta in the cardiac manifestations of Kawasaki disease and led to ongoing phase II clinical trials using anti-IL-1 therapies in children with Kawasaki disease who are unresponsive to IVIG therapy. Through several NIH-funded R01 grants, Arditi and his research team are currently investigating the role of the gut microbiome, the metabolome and secretory IgA in the development of cardiovascular lesions in this model. The team is also investigating the long term complications associated with Kawasaki disease vasculitis, such as myocardial fibrosis.

In addition, the Arditi Laboratory studies the molecular pathogenesis of bacterial infections of the lungs and the role of innate and adaptive immunity in infections and in infection-induced acute and chronic inflammatory diseases, such as allergic asthma, acute and chronic lung injuries and ventilation-induced lung injuries.

Finally, the Arditi Lab also conducts seminal research in cancer immunology. Specifically, researchers in the Arditi Laboratory are investigating the role of the innate immune system in the progression and development of cancer and in metastasis and the role of sex hormones on the tumor microenvironment and metastasis of melanoma to the lungs. The Arditi team is also pursuing the effect of androgen depletion therapy in prostate cancer patients on neutrophil function and the risk for developing secondary cancers, such as melanoma.