Complications (Co-Leaders: Joseph Witztum, Rohit Loomba and Jake Lusis)

Despite advances in the treatment of hyperglycemia, hypertension and hyperlipidemia, the macrovascular and microvascular complications of diabetes are still devastating. Moreover, there is now an epidemic of liver disease associated with obesity and diabetes, that includes hepatic steatosis, NAFLD and liver cancer. Highlights include the following.


  1. Systems biology analysis reveals role of MDM2 in diabetic nephropathy, by DRC member Sharma and others in JCI (2016). Sharma and colleagues show downregulation of MDM2 gene expression in both glomerular and tubulointerstitial compartments of kidney biopsy tissue from patients with diabetic nephropathy. In diabetic mice, chemical inhibition of MDM2 led to reduction in the number of podocytes, identifying an important functional role for MDM2 in glomeruli and tubules of the diabetic nephropathic kidney.
  2. The genetic architecture of NAFLD among inbred strains of mice by DRC member Lusis and others in eLIFE (2015). Genome-wide association studies of inbred mouse strains by Lusis and colleagues revealed three loci associated with hepatic TG accumulation. Analyses of transcript levels, metabolite levels, and gut microbiota composition, provide a framework for understanding genetic and environmental interactions underlying hepatic steatosis.
  3. Origin of myofibroblasts in the fibrotic liver in mice, by DRC members Brenner, Glass and others in PNAS (2014). Brenner, Glass and colleagues found that hepatic stellate cells are the major source of myofibroblasts in liver injury. Gene expression analysis identified several novel markers that may help to identify critical roles in the pathogenesis of liver fibrosis and, therefore, serve as an attractive target for antifibrotic therapy.