RESEARCH INTERESTS



The work in our laboratory is focused on understanding the molecular pathogenesis of viral-associated cancers such as  Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV is associated with a number of human malignancies including Kaposi's sarcoma (KS) and B cell lymphoproliferative diseases such as multicentric Castleman's disease and non-Hodgkin lymphoma i.e. primary effusion lymphoma.  Malignancies associated with KSHV are usually (but not always) seen in the context of immune-suppression i.e. in HIV-infected individuals and transplant patients. KSHV belongs to the gamma-2 (rhadinovirus) grouping of herpesviruses. Herpesviruses are characterized by their ability to persist in either a latent or lytic phase in the host. In latent infection, viral gene expression is limited and the viral genome remains associated with the cell for many generations without virus production. However, during the lytic phase there is a temporal order of viral gene expression resulting in the production of infectious viral progeny. The mechanism by which KSHV induces cellular transformation is currently unknown and our lab is focused on understanding how the virus transforms cells and persists in them. We also study basic cellular and viral mechanisms that determine how KSHV is able to maintain the latent and lytic phases of its lifecycle.
Specific projects are listed as follows:

-We study KSHV viral proteins that are involved in cellular transformation and modulation of cell signaling pathways. These studies involve investigating the effect of viral proteins on cell proliferation, apoptosis and cell signal transduction pathways.
-Kaposi’s sarcoma is a highly angiogenic tumor and we are currently investigating how viral proteins encoded by KSHV are responsible for the induction of angiogenesis.
-We  study host-pathogen interactions, specifically we are looking at how KSHV interacts with the innate immune system.
-Our lab studies viral transcription factors and how they help the virus to replicate and persist in the host cell.
-We are developing therapeutics that curb viral replication and prevent virus persistence. We are also developing drug therapies that target cancer cells.  In this manner we hope to translate basic research into clinical application.
-In addition, we work on the simian homologue of KSHV named rhesus monkey rhadinovirus (RRV). RRV shows high sequence-relatedness to KSHV but unlike its human counterpart can be grown lytically and to high titers in cell culture. This facilitates the making of recombinant viruses that allow us to study the properties of a number of viral genes in the lifecycle of the virus. We use RRV as animal model system to understand KSHV pathogenesis in vivo and in vitro.
-Finally, we are using our knowledge on viral cancers to understand how certain types of non-viral cancers develop in the human population.

In summary, our lab is interested in the study of viral oncogenes and viral transcription factors of KSHV, host-pathogen interactions, innate immunity, and using RRV as an animal model system to study KSHV pathogenesis. The projects in our laboratory encompass the areas of signal transduction, apoptosis, angiogenesis, innate immunity, transcription and recombinant herpesvirus production. We employ the latest techniques in molecular biology, cell biology, immunology and biochemistry to investigate key issues in viral oncogenesis.


We also direct a Program in Global Oncology through the Lineberger Comprehensive Cancer Center at UNC-Chapel Hill to address the growing disparity in cancer incidence and prognosis across the world, especially in developing countries.
Please visit the following website for more information on our global oncology program:
https://unclineberger.org/research/research-programs/global


Please contact us if you are interested in our research  (damania@med.unc.edu)