PhD
Assistant Professor, Cell Biology and Physiology
UNC-Chapel Hill
Cancer Cell Biology
Area of Interest
Our research focuses on the molecular pathways involved in kidney development, function, and disease. Wilms tumor is the most common pediatric renal cancer.
Histological and transcriptomic data suggest that tumors arise from a malignant transformation of progenitor cells during fetal kidney development. Nephron progenitors give rise to all the cell types of the mature nephron, the filtering component of the kidney. Nephron progenitors are normally depleted by birth and no new nephrons are formed thereafter. In the case of blastemal predominant Wilms tumor, it is hypothesized that nephron progenitors harboring somatic mutations do not differentiate normally and undergo malignant transformation.
Recent reports on Wilms tumor have identified specific, recurring mutations in transcriptional regulators normally required for maintaining the nephron progenitor population during development. We are focused on identifying how these mutations lead to the formation and propagation of Wilms tumor. Our interrogation of primary tumor data and in vitro analyses suggest that altered DNA-binding affinity may drive aberrant gene expression in these tumors.
We are currently utilizing kidney organoids to model this disease by genetic introduction of these specific mutations and identifying how transcriptional programs are modified in our organoid model. This novel approach will enable the first insights into how Wilms tumor is initiated during fetal kidney development and help identify targeted therapeutic strategies.
Additional studies include models of malignant rhabdoid tumors of the kidney, where mutations in a single chromatin modifier are responsible for the most lethal and aggressive pediatric renal cancer.
