Approximately 1/3 of all human cancers is of viral origin or requires viral infection as an essential cofactor. The goal of our research is to understand viral cancers; specifically, cancers that are caused by Kaposi sarcoma-associated herpesvirus (KSHV).
KSHV is a double-stranded DNA virus with over 100 open reading frames, which belongs to human herpesviruses. It was discovered in 1994 by Patrick Moore and Yuan Chang. It is associated with Kaposi sarcoma (KS) as well as a B-cell lymphoma and multicentric Castleman’s disease (MCD). These diseases are rapidly fatal as they affect internal organs. In the U.S., KS is seen in the context of immune suppression such as in HIV-positive individuals or transplant patients. In Sub-Saharan Africa HIV-KS is the most common cancer in males and also seen in children.
Our lab is focused on three areas:
1. Viral genomics and bioinformatics – We established the UNC Vironomics core (http://www.med.unc.edu/vironomics), in order to apply genomic technologies, primarily next generation sequencing to viral genomes, and virus gene expression. This includes single cell measurements and it utilizes clinical samples from KS trials that we conducted in the US, South Africa, and in Malawi.
2. Mouse models of viral oncogenesis – We have developed transgenic mice, which express the LANA protein under the control of its own promoter and had previously shown that the LANA promoter exhibits B-lineage specificity in transgenic mice. We use this model in conjunction with specific ko-mice to study the immune regulation by KSHV.
3. Exosomes – This is a new and exciting area of research in the lab. It focusses on 50-120 nm particles, which like viruses carry proteins and miRNAs to neighboring cells and which are intricately linked to viral pathogenesis.
El-Mallawany NK, Kamiyango W, Villiera J, Peckham-Gregory EC, Scheurer ME, McAtee CL, Allen CE, Kovarik CL, Frank D, Eason AB, Caro-Vegas C, Chiao EY, Schutze GE, Ozuah NW, Mehta PS, Kazembe PN, Dittmer DP. Kaposi Sarcoma Herpesvirus Inflammatory Cytokine Syndrome-like Clinical Presentation in Human Immunodeficiency Virus-infected Children in Malawi. Clin Infect Dis. 2019 Nov13;69(11):2022-2025.
McNamara RP, Chugh PE, Bailey A, Costantini LM, Ma Z, Bigi R, Cheves A, Eason AB, Landis JT, Host KM, Xiong J, Griffith JD, Damania B, Dittmer DP. Extracellular vesicles from Kaposi Sarcoma-associated herpesvirus lymphoma induce long-term endothelial cell reprogramming. PLoS Pathog. 2019 Feb 4;15(2): e1007536.
Bigi R, Landis JT, An H, Caro-Vegas C, Raab-Traub N, Dittmer DP. Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48): E11379-E11387.
Sin SH, Eason AB, Bigi R, Kim Y, Kang S, Tan K, Seltzer TA, Venkataramanan R,An H, Dittmer DP. Kaposi’s Sarcoma-Associated Herpesvirus Latency Locus Renders B Cells Hyperresponsive to Secondary Infections. J Virol. 2018 Sep 12;92(19):e01138-18.
Raab-Traub N, Dittmer DP. Viral effects on the content and function of extracellular vesicles. Nat Rev Microbiol. 2017 Sep;15(9):559-572.
Sin SH, Kim Y, Eason A, Dittmer DP. KSHV Latency Locus Cooperates with Myc to Drive Lymphoma in Mice. PLoS Pathog. 2015 Sep 1;11(9):e1005135.
Yang D, Chen W, Xiong J, Sherrod CJ, Henry DH, Dittmer DP. Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma. Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):E4762-8.
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 subtypes of Kaposi’s sarcoma. MBio. 2014 Sep 23;5(5):e01633-14.
Chugh PE, Sin SH, Ozgur S, Henry DH, Menezes P, Griffith J, Eron JJ, Damania B, Dittmer DP. Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies. PLoS Pathog. 2013;9(7):e1003484.
Roy D, Sin SH, Lucas A, Venkataramanan R, Wang L, Eason A, Chavakula V, Hilton IB, Tamburro KM, Damania B, Dittmer DP. mTOR inhibitors block Kaposi sarcoma growth by inhibiting essential autocrine growth factors and tumor angiogenesis. Cancer Res. 2013 Apr 1;73(7):2235-46.
Mutlu AD, Cavallin LE, Vincent L, Chiozzini C, Eroles P, Duran EM, Asgari Z, Hooper AT, La Perle KM, Hilsher C, Gao SJ, Dittmer DP, Rafii S, Mesri EA. In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: a cell and animal model of virally induced Kaposi’s sarcoma. Cancer Cell. 2007 Mar;11(3):245-58.