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Dominic Ciavatta, PhD - Division of Nephrology and Hypertension

Dominic Ciavatta, PhD

Associate Professor of Medicine

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Dominic Ciavatta, PhD

Associate Professor of Medicine

About

Dr. Ciavatta studies anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) to identify the genetic and epigenetic drivers contributing to disease susceptibility and severity. Large-scale genetic studies in humans have identified HLA variants (proteins that present antigens to T cells) more frequently in patients with AAV than healthy individuals, suggesting variants in HLA genes predispose individuals to AAV. Currently his lab is investigating how the HLA variants linked with AAV interact with patient’s T cells. Using a mouse model of AAV, they observed differences in glomerular damage among inbred strains of mice, indicating a genetic component influences disease severity.

Dr. Ciavatta and colleagues also found that patients with AAV differ from healthy individuals at the level of epigenetics–that is, changes that regulate gene activity, independent of the DNA sequence. Epigenetic modifications to DNA and histones (proteins used to compact DNA into a cell’s nucleus) associated with inactive genes are deficient at key genes in patients with AAV. Intriguingly, patients that restore the DNA modifications are less likely to relapse, which suggests a patient’s epigenetic status may predict disease progression. Dr. Ciavatta’s lab is examining genome wide epigenetic changes in patients to understand molecular mechanisms regulating gene activation that are disrupted in AAV.