I recently completed a PhD in Wendy Gilbert’s lab at Yale. I work on RNA modifications, or the ‘epitranscriptome‘. During my PhD, I co-founded a company (Cloverleaf Bio), which is developing therapeutics to inhibit the activity of RNA modifying enzymes and improve patient outcomes in oncology.
My PhD research focused on the development of new methods to find and quantify RNA modifications, and on understanding the mechanisms by which aberrant expression of the enzymes that install these modifications impacts human health. For the first part of my PhD, I developed D-seq, a method to find a specific RNA modification, dihydrouridine in high throughput using sequencing. Using D-seq, we revealed that dihydrouridine is present in a number of unexpected classes of RNA, including snoRNA and mRNA, where it can alter RNA structure and function.
For the second part of my PhD, I studied an enzyme called dihydrouridine synthase 2 (DUS2) which is frequently overexpressed in lung cancer. I showed in human cells and mouse xenografts that DUS2 suppresses ferroptosis, a metal-dependent non-apoptotic form of cell death to which many lung cancers are unusually sensitive. Mechanistically, DUS2 is required to maintain specific tRNA expression and support translation of specific proteins including metallothioneins which serve as key regulators of both metal and redox homeostasis. My results reveal a tRNA-specific vulnerability in lung cancer cells and demonstrate the therapeutic potential of targeting RNA modifying enzymes in cancer.
Before grad school, I worked in Alice Ting’s group, mapping the spatial localization of proteins in mammalian neurons.
In my free time I like to paddle my kayak, and generally explore the outdoors.
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