Liver disease development and progression are dictated by the individual and combined contributions of different genetic and environmental factors. Our previous work in mouse models linked liver injury susceptibility to the function of energy metabolism regulators, including the glycolytic enzyme GAPDH and the purine metabolizing enzymes nucleoside diphosphate kinase (NDPK) and ecto-5'-nucleotidase CD73. Current efforts in the lab are aimed at understanding the regulation and cell-specific functions of CD73 in various stages of liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma.
Our lab studies the molecular basis of liver diseases and disorders linked to intermediate filament gene mutations. We use biochemical, cell-based and in vivo approaches to identify potential disease targets and to understand their function and regulation. The major goal of our work is to promote the discovery of pharmacological agents that can slow or halt the progression of these diseases.
in the Cell Biology and Physiology Department at UNC-Chapel Hill
Energy metabolism regulators in liver pathobiology
Intermediate filaments (IFs) are cytoskeletal structures that perform important mechanical and signaling functions. IF gene mutations are linked to a vast number of human pathologies, including skin fragility disorders, neuropathies, myopathies, liver diseases, metabolic dysfunctions, and premature aging syndromes. Effective treatments for diseases caused by IF gene mutations are lacking. Our long-term goal is to define the proteostasis network of IF proteins and to identify key features that are compromised by disease-causing or disease-promoting mutations. We are currently focused on various post-translational modifications (PTMs) and their cross-talk mechanisms.
The intermediate filament cytoskeleton: biochemical basis of associated diseases