Dr. Michael Lagunoff

My laboratory studies the molecular virology of Kaposi's Sarcoma-associated herpesvirus (KSHV, also known as Human herpesvirus 8, HHV-8). KSHV is the infectious cause of Kaposi's Sarcoma (KS), the most prevalent tumor in AIDS patients. KSHV is also associated with two B-cell lymphoproliferative diseases, primary effusion lymphoma and AIDS-associated multicentric Castleman's disease. Interests in the lab focus on virus host interactions to better understand how the virus causes tumors.

The laboratory is interested in how the KSHV alters the host cell and leads to KS. KSHV encodes many genes involved in altering host cell signal transduction. The laboratory focuses on how initiation of host signal transduction pathways by viral genes leads to viral pathogenesis in endothelial and B-cells. We use molecular virology, biochemistry, immunology and genomics to study the virus host interactions.

1. KSHV induction of oncogenic signaling pathways:
We are interested in how the virus induces specific signal transduction pathways in endothelial cells. We have found that KSHV infection of endothelial cells induces persistent activation of many pathways including STAT3 and AKT, genes known to be activated in many tumor types. Current studies involve the further analysis of the mechanism of chronic activation of signaling by KSHV and the discovery of other signaling pathways activated by KSHV infection.
2. KSHV induction of angiogenesis:
KSHV is likely to play a direct role in the vascularization of the KS tumor. Using microarrays and other techniques we have found that KSHV infection of endothelial cells activates the expression of a number of genes involved in angiogenesis. We are currently characterizing the functional outcomes of these virally induced alterations. For example, we found that KSHV induces hypoxia induced transcription factors (HIFs) leading to activation of VEGF receptor-1. Current work is fousing on the functional outcome of viral induction of the hypoxic response.
3. KSHV induction of blood to lymphatic endothelial cell differentiation:
We found that when blood endothelial cells are infected with KSHV they differentiate into lymphatic endothelial cells. Further studies into the mechanism of virally induced lymphatic endothelial cell differentiation revealed that both STAT3 and AKT signaling are necessary. Further work on this pathway of virally induced differentiation and the effects on KSHV life-cycle .
4. Antiviral discovery
The lab has a secondary focus on anti-herpesviral drug discovery. Together with the Samudrala lab we have discovered a broad spectrum anti-herpesviral compound that inhibits replication of alpha, beta and gamma herpesvirus. Ongoing work is characterizing this novel inhibitor and work on new compounds in continuing.