The major long-term goal of our research studies is to understand the mechanisms by which human cancer-causing herpesviruses interact with the host cell. We study Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated virus (KSHV). EBV has been identified as a cause of Burkitt’s lymphoma, Hodgkin’s lymphoma, lymphomas in transplant recipients, gastric cancer and nasopharyngeal carcinoma. KSHV causes lymphoma in addition to Kaposi’s sarcoma, a malignancy of the blood vessels. Both of these viruses maintain latent infections in their human host but intermittently lead to uncontrolled cellular proliferation that results in cancer. We apply molecular techniques to identify how specific viral gene products modulate cell functions. We introduce targeted genetic changes into the viral DNA, altering or deleting the gene of interest. We developed techniques which allowed the generation of viable EBV viruses (genetic recombinants) that could be used to determine the role of virtually any EBV gene. We have applied these and other methods to study a unique EBV gene, known as the SM gene, that regulates not only EBV genes, but also those of the host cell. The SM protein acts by pirating components of the host cell to facilitate expression of EBV genes and also modulates host gene expression. This work is currently supported by NIH RO1 funding from the National Cancer Institute and we have been consistently funded by the NIH in the field of gammaherpesvirus research for over 25 years.