Lagunoff, Michael

It has been estimated that as many as 20% of human cancers have a viral etiology.  Our lab is interested in how viruses cause cancer.  The laboratory studies the molecular virology of Kaposi's Sarcoma-associated herpesvirus (KSHV). KSHV is the infectious cause of Kaposi's Sarcoma (KS). KS is a highly vascularized hyperplasia that is the most common tumor in AIDS patients and is currently the most commonly reported tumor in regions of Africa. KSHV is also associated with two B-cell lymphoproliferative diseases, primary effusion lymphoma and AIDS-associated multicentric Castleman's disease. The laboratory is interested in how the virus alters the host cell to induce tumors..

The highly vascularized nature of the KS tumor led us to examine if latent KSHV infection can directly induce angiogenesis. Current studies in the lab involve determining how KSHV induces angiogenic phenotypes upon infection of endothelial cells, the main KS tumor cell type.  In additon we discovered that KSHV infection of blood endothelial cells reprograms them to differentiate into lympahtic endohtelium and we are mapping the cellular and viral mechanisms of this virus induced differentiation and examining the the functional outcomes of differentiation for the virus. 

Another main focus of the lab is virally induced alteration of host cell metabolism.  While viruses themselves do not have metabolism, they dramatically alter the host cell metabolism for the benefit of the virus.  We found that KSHV induces the Warburg effect, one effect common to almost all tumor cells.  The Warburg effect is the induction of glycolysis and a decrease in oxidative phosphorylation.  We believe that indcution of the Warburg effect allows rapid adaptation of latently infected cells to tumor environments allowing the expansion of latency.  We  are  examinaed global changes in metabolic pathways induced by KSHV using a metabolomics approach.  We hope to be able to use  inhibitors of pathologic metabolic changes to inhibit viral latency and spread.   Through a better understanding of how KSHV induces pathologic metabolic changes we hope to be better identify target pathways.