The focus of my research is to define genetic interactions with the TAFAZZIN gene in mammalian cells. Barth syndrome (BTHS) is a genetic disorder caused by a disruption of a single gene, TAFAZZIN. Mutations in this gene can cause partial or total loss of function of the tafazzin enzyme. The primary molecular consequence of tafazzin deficiency is aberrant cardiolipin (CL) metabolism. CL is the signature phospholipid of the mitochondria and plays a major role in the maintenance of many cellular processes. Although recent work has identified many dysregulated cellular processes associated with BTHS, the fundamental molecular mechanism underlying the disease pathophysiology remains unknown. I am using the latest CRIPSR/Cas9 technology to carry out a whole genome screen in tafazzin-deficient mammalian cells. This screen will identify cellular pathways that are altered in the absence of tafazzin, including those previously not associated with the disease. This information will stimulate new research directions for understanding and treating BTHS.
I am also very interested in the study of lipids and redox-active biomolecules. Current data shows that many BTHS cell models show increased reactive oxygen species (ROS) production. My hope is that the CRISPR screen leads to the identification of candidate pathways that could potentially explain the role of ROS in BTHS.
