Boshamer Distinguished Professor
Vice Dean for Research
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.
- 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.
- 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.
1) 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
2) Host KM, Horner MJ, van der Gronde T, Moses A, Phiri S, Dittmer DP, Damania B, Gopal S. Kaposi’s sarcoma in Malawi: a continued problem for HIV-positive and HIV-negative individuals. AIDS. 2017 Jan 14;31(2):318-319.
3) Hsia HC, Stopford CM, Zhang Z, Damania B, Baldwin AS. Signal transducer and activator of transcription 3 (Stat3) regulates host defense and protects mice against herpes simplex virus-1 (HSV-1) infection. J Leukoc Biol. 2016.
4) Anders PM, Zhang Z, Bhende PM, Giffin L, Damania B. The KSHV K1 protein modulates AMPK function to enhance cell survival. PLoS Pathogens. 2016. 12(11).
5) Baric, RS, Crosson S, Damania B, Miller, SI, Rubin EJ. Next-Generation High-Throughput Functional Annotation of Microbial Genomes. MBio. 2016. 7(5).
6) Dittmer DP, Damania B. Kaposi sarcoma associated herpesvirus: immunobiology, oncogenesis and therapy. J. Clin. Invest. 2016. 126(9): 3165-75
7) Bhatt AP, Wong JP, Weinberg MS, Host KM, Giffin LC, Buijnink J, van Dijk E, Izumiya Y, Kung HJ, Temple BR, Damania B. A viral kinase mimics S6 kinase to enhance cell proliferation. Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7876-81.
8) Zhang Z, Chen W, Sanders MK, Brulois KF, Dittmer DP, Damania B. The K1 Protein of Kaposi’s Sarcoma-Associated Herpesvirus Augments Viral Lytic Replication. J Virol. 2016 Aug 12;90(17):7657-66.
9) Guo H, König R, Deng M, Riess M, Mo J, Zhang L, Petrucelli A, Yoh SM, Barefoot B, Samo M, Sempowski GD, Zhang A, Colberg-Poley AM, Feng H, Lemon SM, Liu Y, Zhang Y, Wen H, Zhang Z, Damania B, Tsao LC, Wang Q, Su L, Duncan JA, Chanda SK, Ting JP. NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses. Cell Host Microbe. 2016 Apr 13;19(4):515-28.
10) Ma, Z and Damania, B. The cGAS-STING Defense Pathway and Its Counteraction by Viruses. Cell Host Microbe. 2016. Feb 10; 150-158.
11) Damania, B. A Virological Perspective on Cancer. PLoS Pathog. 2016 Feb 11;12(2):e1005326.
12) Giffin L, West JA, Damania B. Kaposi’s Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration. MBio. 2015 Dec 8;6(6):e01499-15
13) Jacobs SR, Stopford CM, West JA, Bennett CL, Giffin L, Damania B. KSHV vIRF1 interacts with a member of the Interferon Stimulated Gene 15 pathway. J Virol. 2015
14) Ma, Z, Jacobs, SR, West, JA, Stopford, C, Zhang, Z, Davis, Z, Barber, GN, Glaunsinger, BA, Dittmer DP, and B. Damania. Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proceedings of the National Academy of Sciences (PNAS). 2015.
15) Walker, MP, Stopford, CM, Rabinowitz,AR, Goldfarb,G, Yan, F, Fedoriw, Y, Richards, KL, Damania, B, and Major, MB. FOXP1 Activates Wnt Signaling in Diffuse Large B-cell Lymphoma. Science Signaling. 2015. Feb 3;8(362):ra12.
16) Sun C, Schattgen SA, Pisitkun P, Jorgensen JP, Hilterbrand AT, Wang LJ, West JA, Hansen K, Horan KA, Jakobsen MR, O’Hare P, Adler H, Sun R, Ploegh HL, Damania B, Upton JW, Fitzgerald KA, Paludan SR. Evasion of Innate Cytosolic DNA Sensing by a Gammaherpesvirus Facilitates Establishment of Latent Infection. J Immunol. 2015.
17) Hosseinipour, MC, Sweet, KM, Xiong, J, Namarika,D, Mwafongo, A, Nyirenda, M, Chiwoko,L, Kamwendo, D, Hoffman, I, Lee, J, Phiri, S, Vahrson, W, Damania, B, Dittmer, DP. Viral profiling identifies multiple sub-types of Kaposi sarcoma. mBIO. 5(5):e01633-14.
18) Giffin, L. Yan, F., Major, MB and B. Damania. Modulation of KSHV vIL-6 function by Hypoxia Upregulated Protein 1. J Virol. 2014;88(16):9429-41.
19) Zhang, L, Mo, J, Seanson, KV, Wen, H, Petrucelli, A, Gregory, SM, Zhang, Z, Schneider, M, Jiang, Y, Fitzgerald, K, Ouyang, S, Liu, ZJ, Damania, B., Shu, HB, Duncan, JA, Ting, JP. . NLRC3, a Member of the NLR Family of Proteins, Is a Negative Regulator of Innate Immune Signaling Induced by the DNA Sensor STING. Immunity. 2014.
20) West, JA, Wicks, M, Gregory, SM, Chugh, P, Jacobs, SR, Zhang, Z, Host, KM, Dittmer, DP, and B. Damania. An important role for MAVS in the KSHV lifecycle. J. Virology. 2014.
21) Meckes DG Jr, Gunawardena HP, Dekroon RM, Heaton PR, Edwards RH, Ozgur S, Griffith JD, Damania B, Raab-Traub N. Modulation of B-cell exosome proteins by gamma herpesvirus infection.Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):E2925-33.
22) Dillon PJ, Gregory SM, Tamburro K, Sanders MK, Johnson GL, Raab-Traub N, Dittmer DP, Damania B. Tousled-like Kinases Modulate Reactivation of Gammaherpesviruses from Latency. Cell Host Microbe. 2013 Feb 13;13(2):204-14.
The principal investigator, Dr. Blossom Damania, has been the recipient of the following:
- V Foundation Scholar Award (2001)
- American Herpes Foundation Research Scholar Award (2003)
- AACR-Gertrude Elion Scholar Award (2004)
- Leukemia & Lymphoma Society Scholar (2005-2010)
- Jefferson-Pilot Junior Faculty Award in Academic Medicine (2005)
- American Heart Established Investigator Award (2006-2011)
- Burroughs-Wellcome Fund Investigator in Pathogenesies of Infectious Disease (2006-2011)
- Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement, 2008.
- Dolph O. Adams Award, Society for Leukocyte Biology, 2011.
- Kavli Fellow, National Academy of Sciences, USA. 2011.
- Fellow of the American Academy of Microbiology, 2013
- Cary C. Boshamer Distinguished Professorship, UNC Chapel Hill, 2015
- Achievement Award, Mount Holyoke College, 2017