February 2, 2022

Regulation of Cellular Metabolism

EBV upregulates several cellular metabolic pathways to promote proliferation of infected B cells. Our work has focused on the mechanisms responsible for increased glycolysis and oxidative phosphorylation. We recently published a collaborative study with Heather Christofk’s lab at UCLA and Mark Parnell of Vettore Bio demonstrating how EBV tolerates elevated glycolysis stimulated by EBNA2 and MYC during latent infection. The upregulation of the lactate transporters, MCT1 and MCT4, were critical in maintaining EBV-infected cell proliferation. Moreover, combined antagonism revealed a heightened sensitivity to electron transport chain inhibitors such as phenformin and metformin. We are now pursuing both mechanistic and pre-clinical animal studies of MCT inhibition in EBV-infected lymphomas. Check out one of our papers here!

We are also characterizing the role of the viral EBNA-LP transcription factor in regulating OXPHOS through mimicry of the PGC-1 coactivator proteins in driving transcriptional upregulation through NRF1, ERRa, and YY1. This work along with further genetic and biochemical characterization of EBNA-LP is being done in collaboration with Rob White (Imperial College London), Maria Schumacher (Duke Biochemistry), and Johanna Myllyharju (University of Oulu, Finland).

 

 

 

 

 

 

Jana                               Ali                           Marc