Boshamer Distinguished Professor
Vice Dean for Research
Viruses, Cancer, & Immunity
We study how viruses cause cancer and evade host immunity. We also investigate new approaches for treating viral and non-viral cancers.
Globally, it is estimated that between 15-20% of all cancers are associated with oncogenic viruses. These include EBV, KSHV, HPV, HCV, HBV, MCV and HTLV. The work in our laboratory is focused on understanding the molecular pathogenesis of different oncogenic viruses. We study several oncogenic human viruses including, but not limited to, 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. Both Epstein-Barr virus (EBV) and KSHV are gammaherpesviruses. 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 specific mechanisms as to how these viruses induce cellular transformation are under investigation 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 these viruses are able to maintain the latent and lytic phases of its lifecycle.
Specific projects are listed as follows:
- We study 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 the virus interacts with the innate immune system.
- 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.
- 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, viral transcription factors, host-pathogen interactions, and innate immunity. 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.
Gregory, S. West, JA, Dillon, PJ, Hilscher, C.,Dittmer,DP and B. Damania. Toll like receptor Signaling controls reactivation of KSHV from latency. 2009. PNAS. 106(28):11725-30.
Gregory,SM, Davis,BK., West, JA., Taxman, D., Matsuzawa, S., Reed, J., Ting. JP, and B. Damania. Discovery of a Viral NLR homolog that Inhibits the Inflammasome. Science. 2011. 331(6015):330-4.
Dillon, PJ, Gregory, SM, Tamburro, K, Sanders, M, Johnson, GL, Raab-Traub, N, Dittmer, DP, and B. Damania. Tousled-like Kinases Modulate Reactivation of Gammaherpesviruses from Latency. Cell Host & Microbe. 2013. 13(2):204-14.
Ma, Z, Jacobs, SR, West, J., Stopford, CM, Davis, Z, Glaunsinger, B, Dittmer, DP and B. Damania. Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proceedings of the National Academy of Sciences (PNAS). 112(31):E4306-15. doi: 10.1073/pnas.1503831112
Bhatt, AP, Wong, JP., Weinberg, MS, Host, KM, Giffin, LC, Buijninkc, J., van Dijkc, E., Izumiya, K, Kung,HJ, Temple, B, and B. Damania. A viral kinase mimics S6 kinase to enhance cell proliferation. PNAS. 2016. Jul 12;113(28):7876-81. doi: 10.1073/pnas.1600587113.
Anders, PM, Zhang,Z, Bhende,PM, Giffin,LC and B. Damania. The KSHV K1 Protein Modulates AMPK Function to Enhance Cell Survival. PLoS Pathogens. 2016. 12(11):e1005985. doi:10.1371/journal.ppat.1005985.
Ma Z, Hopcraft SE, Yang F, Petrucelli A, Guo H, Ting JP, Dittmer DP, Damania B. NLRX1 negatively modulates type I IFN to facilitate KSHV reactivation from latency. PLoS Pathog. 2017 May 1;13(5):e1006350.
Host KM, Jacobs SR, West JA, Zhang Z, Costantini LM, Stopford CM, Dittmer DP, Damania B. Kaposi’s Sarcoma-Associated Herpesvirus Increases PD-L1 and Proinflammatory Cytokine Expression in Human Monocytes. MBio. 2017 Oct 10;8(5).
Anders PM, Montgomery, ND, Montgomery, SA, Bhatt, AP, Dittmer, DP and Damania, B. (2018) A human herpesvirus encoded kinase induces B cell lymphomas in vivo. Journal of Clinical. 2018 Jun 1;128(6):2519-2534.
Cesarman, E, Damania, B, Krown, SE, Martin, J, Bower, M and D. Whitby. Kaposi Sarcoma. Nature Reviews Disease Primer. 2019. 5(1):9.
Wong, JP, Stuhlmiller, TJ, Giffin, LC, Lin, C, Bigi, R, Zhao, J, Zhang W, Bravo Cruz, AG, Park, SI, Earp, HS, Dittmer, DP, Frye, SV, Wang, X, Johnson, GL, Damania, B. Kinome profiling of Non-Hodgkin Lymphoma identifies Tyro3 as a therapeutic target in PEL. 2019. PNAS.
Rivera-Soto R, Dissinger NJ, Damania B. Kaposi’s Sarcoma-associated Herpesvirus Viral Interleukin 6 Signaling Upregulates Integrin Beta 3 Levels and is Dependent on STAT3. J Virol. 2019.
Ni G, Ma Z, Wong JP, Zhang Z, Cousins E, Major MB, Damania B. PPP6C Negatively Regulates STING-Dependent Innate Immune Responses. mBio. 2020 Aug 4;11(4):e01728-20.
Zhang H, Ni G, Damania B. ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway. Cell Rep. 2020 Apr 28;31(4):107564.