There are currently over 1200 rare, inherited metabolic dysfunctions that are collectively known as “Inborn Errors of Metabolism (IEM)”. These disorders stem from an inactive enzyme (e.g. enzyme phenylalanine hydroxylase in phenylketonuria) in a metabolic pathway, often leading to toxic accumulation of metabolites upstream of the defective enzyme. There are no FDA-approved drugs for a majority of these diseases primarily because of our lack of understanding of the pathophysiology. To address this challenge, our lab employs a multidisciplinary approach to decipher how an inactive enzyme in IEM impacts cellular and organismal physiology. We are also exploring different strategies (chemical, genetic, and enzyme-based) to re-establish metabolic homeostasis in IEM and assessing the therapeutic benefits of such interventions.
In two other projects, we are investigating: (a) chemical strategies to restore mitochondrial homeostasis in mitochondrial DNA (mtDNA) mutation disorders and (b) how declining NAD+ levels affect cellular physiology in aging and neurodegeneration using proteomics and metabolomics.
For more visit The Patgiri Lab.