Our Research

Work in the Morizono Laboratory has been rooted in categorizing and understanding the biological scales and mechanisms by which mutations in urea cycle enzymes cause disease and developing therapies to treat disorders of nitrogen metabolism. Hiroki Morizono, Ph.D., has a deep-seated interest in the relationships between sequence, structure and function of proteins that govern how an amino acid sequence folds into a particular three-dimensional shape. The lab seeks to answer the questions: Which regions of a protein are affected when mutations occur, and how do mutations affect its catalytic activity? Insights into these questions let us develop predictions about potential severity of inherited disease and forms the basis for understanding how the different proteins and enzymes interact in our cells and bodies. 

From there, the lab has included genome-wide analyses of mutations that perturb metabolism and developed preclinical gene therapy approaches to treat ornithine transcarbamylase and N-acetylglutamate synthase deficiency. Work with the Clinical and Translational Science Institute at Children's National Hospital has led to close collaborations with teams at Children’s National Hospital and the George Washington University to extract data from local and national health records so they are available for data mining. Most recently, we have developed a concept of “criticality,” a severity measure of care intensity in the pediatric intensive care unit using a machine learning approach, and in collaboration with colleagues at GW and AWS, refined a cloud computing solution called Service Workbench designed to provide secure, repeatable, and federated control of access to data, tooling and computing power that researchers need.