Our lab is spearheading multiple projects aimed at understanding how iron-sulfur (Fe-S) cluster biogenesis maintains human health when working and contributes to pathology when impaired.
To this end, we marry cutting edge high-content genetic approaches with cell biology and biochemistry techniques; surveying broadly and understanding deeply.
What are the entire suit of human proteins that bind and require Fe-S clusters?
To date, we know several tens of human proteins that bind and require Fe-S clusters; these proteins play key roles in processes such as DNA repair and replication, translation and metabolism. However, new Fe-S cluster proteins are being discovered all the time. This begs the question, can we systematically obtain a complete ledger of all human Fe-S binding proteins?
How is Fe-S cluster synthesis regulated to match supply with demand?
Over the past two decade, enormous strides have been made in delineating the Fe-S cluster synthesis machinery. But how is this machinery regulated? How is the need for Fe-S clusters in the eukaryotic cell, which can originate from many different intracellular compartments, tallied up and relayed back to the biosynthesis machinery?
How is the human cell rewired once Fe-S cluster synthesis is defective in disease?
There are several human diseases that result from mutations in the Fe-S cluster biosynthesis machinery. We use emerging genomic editing tools to model these diseases, as well as systematically understand how the cell is altered in these aberrant states. Can we parse out which alterations are beneficial and which are detrimental to the diseased cell? Moreover, can we shed light on why some tissues are so exquisitely sensitive to changes in Fe-S cluster biosynthesis, while others are more robust to these perturbations?