Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder, characterized by episodes of systematic inflammatory symptoms that can lead to death in severe cases. The etiology of HHV-8 negative MCD is unknown. We hypothesize that genetic mutations (inherited or acquired) contribute to the initiation and progression of MCD. By performing and analyzing whole-genome sequencing data of a cohort of MCD patients, we have identified a mutation in the FAS gene in a familial case (Baker et al). We are currently characterizing additional candidate gene mutations affecting various immune pathways. We are closely collaborating with the Castleman Disease Collaborative Network on this project.

Clonal expansion of blood cells carrying acquired mutations in epigenetic modifier genes, such as DNMT3A and TET2, is common in older adults. This phenomenon, referred to as age-related clonal hematopoiesis, is associated with increased risks of blood cancers and cardiovascular disease. Molecular mechanisms underlying these disease associations are poorly understood. Our group investigates the pathogenic mechanisms of DNMT3A and TET2 mutations, and their roles in promoting blood cancers and atherosclerosis. In particular, we are interested in understanding the impact of these mutations on DNA methylation and immune gene expression. We utilize primary immune cells from donors as well as human pluripotent stem cell-derived immune cells for this research.