Last Updated: 5/3/2010

Clinical Interests
We are interested in identifying new therapies for viral and non-viral lymphomas.

Research Interests
The work in our laboratory is focused on understanding the molecular pathogenesis of Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is associated with a number of human malignancies including Kaposi's sarcoma (KS) and lymphoproliferative diseases such as body cavity-based lymphomas, primary effusion lymphomas, and multicentric Castleman's disease. 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.
Our lab studies viral transcription factors and how they help the virus to replicate and persist in the host cell. We are also involved in characterizing the promoter elements that regulate viral gene expression.
We also 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.
We are also working on developing therapeutics that curb viral replication and prevent virus persistence that will allow us to translate basic research into clinical application.
In summary, our lab is interested in the study of viral oncogenes and viral transcription factors of KSHV, 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, transcription and recombinant herpesvirus production. We employ the latest techniques in molecular biology, cell biology and biochemistry to investigate key issues in viral oncogenesis.
For more information and to download our publications, please visit our lab website: http://www.unc.edu/~damania/

Recent Accomplishments and Honors
The Principal Investigator 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 Award in Faculty Medicine (2005)
-American Heart Association Established Investigator Award (2006-2011)
-Burroughs Welcome Fund Investigator in Infectious Disease (2006-2011)
-2008 Phillip and Ruth Hettleman Prize for Scholarly and Artistic Achievement

Training
B.A., Mount Holyoke College, MA. 1992.
Ph.D., University of Pennsylvania, PA. 1998.
Postdoctoral Fellow, Harvard Medical School, MA. 1998-2000.
Assistant Professor at UNC-Chapel Hill (October, 2000- June 2006).
Associate Professor at UNC-Chapel Hill since July, 2006

Publications
52) Bhatt, AP, Bhende, PM, Sin, SH, Roy, D, Dittmer, DP and B. Damania. Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas. Blood. 2010. (In press).
51) Wen, K and B. Damania. HSP90 and HSP40/Erdj3 are required for the expression and anti-apoptotic function of KSHV K1. Oncogene. 2010. (In press).
50) West JA, Damania B. Kaposi's sarcoma-associated herpesvirus and innate immunity.Future Virol. 2010 Mar 1;5(2):185-196.
49) Gregory SM, Damania B. KSHV and the toll of innate immune activation. Cell Cycle. 2009 Oct 15;8(20):3246-7.
48) González CM, Wang L, Damania B. KSHV Encodes a Viral Deubiquitinase. J Virol. 2009 Oct;83(19):10224-33.
47) Wen KW, Damania B. Kaposi sarcoma-associated herpesvirus (KSHV): Molecular biology and oncogenesis. Cancer Lett. 2009.
46) Wen, KW, Dittmer, DP and B. Damania. Disruption of LANA in rhesus rhadinovirus generates a highly lytic recombinant virus. J Virol. 2009 Oct;83(19):9786-802.
45) Gregory SM, West JA, Dillon PJ, Hilscher C, Dittmer DP, Damania B. Toll-like receptor signaling controls reactivation of KSHV from latency. Proc Natl Acad Sci U S A. 2009 Jun 29.
This article was highlighted in Science Signaling: L. Bryan Ray. For Whom the Toll-Like Receptor Signals. Sci. Signal.,Vol. 2, Issue 80, p. ec242
44) O'Hara AJ, Chugh P, Wang L, Netto EM, Luz E, Harrington WJ, Dezube BJ, Damania B, Dittmer DP. Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma. PLoS Pathog. 2009 Apr;5(4). Website: http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000389
43) O'Hara AJ, Wang L, Dezube BJ, Harrington WJ Jr, Damania B, Dittmer DP. Tumor suppressor micro RNAs are underrepresented in primary effusion lymphoma and Kaposi sarcoma.
Blood. 2009 Feb 27.
42) Wang, L. and B. Damania. KSHV confers a cell survival advantage to endothelial cells. Cancer Research. 2008. 68(12):4640-8.
This article was highlighted in Nature Reviews Cancer: Angiogenesis: Survival of the Infected. Vol.8, page 569 (August 2008).
This article was also featured in the August 2008 Signaling Gateway Highlights section: http://www.signaling-gateway.org/update/updates/200808/index.html
41) Tomlinson, CC and B. Damania.A critical role for endocytosis in the regulation of signaling by the KSHV K1 protein. J. Virology. 2008. 82(13):6514-23.
40) West, J. and B. Damania. Upregulation of the TLR3 pathway by Kaposi's sarcoma-associated herpesvirus during primary infection. J. Virology. 2008. 82(11):5440-9.
39) Nun, T.K., Kroll D.J.,Oberlies,N.H., Soejarto, DD, Case, RJ, Piskaut, P.,Matainaho, T., Hilscher, C., Wang, L., Dittmer, DP., Gao, SJ and B. Damania. Development of a Novel, High Throughput Assay to Screen Anti-Viral Drugs against Kaposi’s Sarcoma-Associated Herpesvirus. Molecular Cancer Therapeutics. 2007. Aug;6(8):2360-70.
38) Mark, L. Spiller, Okroj, Chanas, Aitken, Wong,S., Damania,B., Blom,H and D. Blackbourn. Molecular characterization of the Rhesus Rhadinovirus (RRV) ORF4 gene and the RRV complement control protein (RCP) it encodes. J Virol. 2007 Apr;81(8):4166-76.
37) Hoon-Sin,S., Roy,D., Wang,L., Staudt M.R., Fakhari,FD., Patel,DD. Koon,H., Damania, B. and D.P. Dittmer. Rapamycin is efficacious against primary effusion lymphoma (PEL). Blood. 2007 Mar 1;109(5):2165-73.
36) Damania B. DNA tumor viruses and human cancer. Trends in Microbiology. 2007.
35) Wang, L., Dittmer, D. P., Tomlinson, C.C., Fakhari, F.D. and B. Damania. “Immortalization of primary endothelial cells by the K1 protein of Kaposi’s sarcoma-associated herpesvirus (KSHV). 2006. Cancer Research. 66(7):3658-66.
34) Bowser, B.S., Song, M.J., Sun, R., Morris, S. and B. Damania. “Identification of Multiple Rta Responsive Elements in the KSHV K1 promoter.” 2006. Virology. 348(2):309-27.
33) Gonzalez, C.M., Wong, E.L., Bowser, B.S., Hong, G, Kenney S. and B. Damania. Identification and Characterization of the KSHV Orf49 Protein. 2006. J. Virology. 80(6):3062-70.
32) Wong, E.L. and B. Damania. Transcriptional Regulation of the Kaposi’s Sarcoma-Associated Herpesvirus K15 Gene. 2006. J. Virology;80 1385-1392.
31) Bilelo, J., Morgan, J. Damania, B., Lang, S, and RC Desrosiers. A Genetic System for Rhesus Monkey Rhadinovirus: Use of Recombinant Virus to Quantitate Antibody-Mediated Neutralization. 2006. J. Virology;80 1549-1562.
30) Hong, G., Kumar, P., Wang, L., Damania, B., Gulley, M.L., Delecluse H-J., Polverini, P., and S. Kenney. Epstein-Barr Virus Lytic Infection is Required for Efficient Production of the Angiogenesis Factor VEGF in Lymphoblastoid Cell Lines. J Virol. 2005 79(22):13984-92.
29) Wong, E.L. and B. Damania. Linking KSHV to Human Cancer.2005. Current Oncology Reports (5):349-356.
28) Dittmer, D.P., Gonzalez C.M., Vahrson, W., DeWire, S.M., and B. Damania. “Whole-Genome Transcription Profiling of Rhesus Monkey Rhadinovirus.” 2005. Journal of Virology 79: 8637-8650.
27) Cai, W., Lu, S., Zhang, Z., Gonzalez, C.M., Damania B., and B. Cullen. Kaposi’s sarcoma associated herpesvirus expresses an array of novel viral microRNAs in latently infected cells. 2005.
Proc. Natl. Acad. Sciences. 2005. 102(15):5570-5.
26) DeWire, S. and B. Damania. “The Latency-Associated Nuclear Antigen of Rhesus Monkey Rhadinovirus (RRV) Inhibits Viral Replication through Repression of Orf50/Rta Transcriptional Activation.” J. Virol. 2005. 79; 3127-3138.
25) Payton ME, d'Offay JM, Prado ME, Black DH, Damania B, White GL, Eberle R. Comparative transmission of multiple herpesviruses and simian virus 40 in a baboon breeding colony. Comp Med. 2004. 54(6):695-704.
24) Pagano, J.S. Blaser, M. Buendia, M.A., Damania, B., Khalili, K. Raab-Traub, N., Roizman, B. Validation Of A Causal Relationship: Criteria To Establish Etiology of Viral Cancers. Seminars in Cancer Biology. Semin Cancer Biol. 2004. 14(6):453-71.
23) Damania, B. Oncogenic Gammaherpesviruses: Comparison of Viral Proteins involved in Tumorigenesis.
Nature Reviews Microbiology, 2004. Vol. 2, pp.656-668.
22) Damania, B. Modulation of cell signaling pathways by Kaposi’s Sarcoma-Associated Herpesvirus (KSHV/HHV-8). Cell Biochemistry & Biophysics, 2004.Vol. 40, pp. 305-322
21) Wang, L., Wakisaka N., Tomlinson, C., DeWire S., Krall, S., Pagano, J. and B. Damania. "The Kaposi’s Sarcoma-Associated Herpesvirus (KSHV/HHV8) K1 Protein Induces Expression of Angiogenic and Invasion Factors." Cancer Research.2004. 64. pp.2774-2781.
20) Damania B., J. H. Jeong, B. S. Bowser, S. M. DeWire and D. P. Dittmer. “A Functional Comparison of Rta Transactivator Proteins of Gamma-2 Herpesviruses.” J.Virol. 2004. 78. p.5491-5499.
19) Tomlinson, C.C., and B. Damania. The K1 Protein of Kaposi’s Sarcoma-Associated Herpesvirus Activates the Akt Signaling Pathway. J. Virol. 2004. 78 (4): 1918-27.
18) O’Connor, C., Damania, B. and Kedes, D.H. Capsid. De Novo Infection with Rhesus Monkey Rhadinovirus Leads to the Accumulation of Multiple Intranuclear Capsid Species during Lytic Replication but Favors the Release of Genome-Containing Virions. J Virol. 2003 Dec 15;77(24):13439-13447.
17) Yu, X.K., O’Connor, C., Atanosov, I., Damania, B., Kedes, D., and Z.H. Zhou. Three-Dimensional Structures of the A, B, and C Capsids of Rhesus Monkey Rhadinovirus: Insights into Gammaherpesvirus Capsid Assembly, Maturation, and DNA Packaging. J Virol. 2003 Dec 15;77(24):13182-13193.
16) DeWire, S.M., Money, E.S., Krall, S.P., and B. Damania. Rhesus Monkey Rhadinovirus (RRV): Construction of a RRV-GFP Recombinant Virus and the Development of Assays to Assess Viral Replication. 2003. Virology. 312 (1): 122-134.
15) Bowser, B.S., DeWire, S. and B. Damania. Transcriptional Regulation of the KSHV K1 viral gene of Kaposi’s sarcoma-associated herpesvirus. 2002.Journal of Virology, 76 (24): 12574-12583.
14) DeWire, S., McVoy,, M., and B. Damania. Kinetics of Expression of Rhesus Monkey Rhadinovirus (RRV) and the Identification and Characterization of a polycistronic transcript encoding the RRV Orf 50/Rta, RRV R8 and R8.1 genes. 2002.Journal of Virology, 76(19): 9819-9831.
13) Damania, B. and R.C. Desrosiers. Oncogenic gamma-herpesviruses. Philosophical Transactions of the Royal Society.2001.
12) Choi JK, Means R, Damania B., and J.U. Jung. Molecular piracy of Kaposi’s sarcoma associated herpesvirus.2001. Cytokine and Growth Factor Rev. 12(2-3):245-257.
11) Damania, B and J.U. Jung. Comparative analysis of the transforming mechanisms of Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, and Herpesvirus saimiri.
2000. Advances in Cancer Research, 80:51-82.
10) Li, M., Damania, B. Alvarez, X., Ogryko, G., Ozato, K., and J.U. Jung. The Kaposi sarcoma herpesvirus vIRF gene inhibits histone acetyltransferases. Molecular & Cellular Biology. 20(21):8254-63. 2000.
9) Lee, B.S., Damania, B., and J.U. Jung. The Kaposi's sarcoma-associated herpesvirus K1 and Rhesus Monkey Rhadinovirus R1 proteins. EBV Report. 1999. Vol. 6 (5), pp. 123-125.
8) Alexander, L., Denekamp, L., Auerbach, M., Knappe, A., Damania, B. and R.C. Desrosiers. Sequence analysis of Rhesus Rhadinovirus Isolate H26-95.Journal of Virology, 2000 76 (8).
7) Damania, B. DeMaria, M., Jung, J.U. and R.C. Desrosiers Activation of lymphocyte signaling by the R1 protein of Rhesus monkey rhadinovirus.Journal of Virology, 2000 (76)6.
6) Damania, B., Choi, J.K. and Jung J.U. Gammaherpesviruses: Transforming functions of the first open reading frames. J. Virol. 1999.Journal of Virology, 2000. 76 (4).
5) Damania, B. Lee, H. and Jung, J.U. Primate herpesviral oncogenes. Mol. Cells, 1999. Vol. 9 (4), pp. 20-24.
4) Damania B, Li M, Choi JK, Alexander L, Jung JU, Desrosiers RC. Identification and characterization of the R1 oncogene and its protein product from the rhadinovirus of rhesus monkeys. J. Virol., 1999. Vol. 73(6), pp. 5123-5133.
3) Damania B, Lieberman P, Alwine JC. Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element. Mol Cell Biol. 1998 Jul;18(7):3926-35.
2) Damania B, Mital R, Alwine JC. Simian virus 40 large T antigen interacts with human TFIIB-related factor and small nuclear RNA-activating protein complex for transcriptional activation of TATA-containing polymerase III promoters. Mol Cell Biol. 1998 Mar;18(3):1331-8.
1) Damania B, Alwine JC. TAF-like function of SV40 large T antigen. Genes Dev. 1996 Jun 1;10(11):1369-81.

E-mail: damania@med.unc.edu
Telephone: (919) 843 6011
Address: Rm 31-303 LCCC Chapel Hill, NC
URL: www.unc.edu/~damania/

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