Professor American Cancer Society Research Professor Office Location: HCCLB 1.8a 5117 Centre Avenue Pittsburgh, PA 15213-1863 Contact Information: Office Phone: (412) 623-7721 Fax: (412) 623-7715 Email Address: yc70@pitt.edu Research Interests: Our laboratory performs basic and applied research on viral oncogenesis with efforts focused in the following three areas. First, Merkel cell carcinoma and Merkel cell polyomavirus - We recently discovered a new human polyomavirus, that we call Merkel cell polyomavirus (MCV). This virus is etiologically associated with a rare, but one of the most clinically aggressive skin cancers in humans. We are currently involved in the primary characteristics of this virus including transcript mapping, transforming properties, origin replication, transmission, and seroepidemiologic studies. Second, Kaposi's sarcoma-associated herpesvirus (KSHV) - We are investigating biologic properties of KSHV, the eighth human herpesvirus, also identified in our laboratory. KSHV causes Kaposi's sarcoma, the most common AIDS-associated malignancy as well as a B-cell lymphoma. Through extensive molecular piracy, the virus has incorporated numerous genes, which affect cell proliferation pathways, apoptosis, cell cycle regulation and immune modulation. Finally, New Pathogen Discovery - We continue to be interested in the search for new pathogens in human diseases and have developed new methodologies, which utilize information gained from the Human Genome Project, as well as advanced sequencing technologies. Selected Publications: Dresang LR, Teuton JR, Feng H, Jacobs JM, Camp II DG, Purvine SO, Gritsenko MA, Li Z, Smith RD, Sudgden B, Moore PS, Chang Y. Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes. BMC Genomics 2011; 12(1):625. Shuda M, Kwun HJ, Feng H, Chang Y, Moore PS. Merkel Cell Polyomavirus Small T Antigen Is a PP2A-independent Human Oncoprotein Targeting the Translation Regulator 4E-BP1. J Clin Invest, 2011 doi:10.1172/JCI46323. Feng H, Kwun HJ, Liu X, Gjoerup O, Stolz DB, Chang Y, Moore PS. Cellular and viral factors regulating Merkel cell polyomavirus replication. PLoS One, 2011 6(7): e22468. Tolstov YL, Knauer A, Chen JG, Kensler TW, Kingsley LA, Moore PS, Chang Y. Asymptomatic primary Merkel cell polyomavirus infection among adults. Emerg Infect Dis, 2011 17(8). Moore PS, Chang Y. KSHV: forgotten but not gone. Blood, 2011 117(26): 6973-6974. Harrison XJ, Meinke G, Kwun HJ, Rogalin H, Phelan P, Bullock P, Chang Y, Moore PS, Bohm A. Asymetric assembly of Merkel cell polyomavirus large T-antigen origin binding domains at the viral origin. J Mol Bio, 2011 409(4): 529-542. Liu X, Hein J, Richardson SCW, Basse PH, Moore PS, Gjoerup O, Chang Y. Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human VAM6P to the nucleus. J Biol Chem, 2011 May 13;286(19):17079-90. Kwun HJ, Ramos da Silva S, Qin H, Ferris RL, Tan R, Chang Y, Moore PS. The central repeat domain 1 of Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) prevents cis MHC class I peptide presentation. Virology, 2011 Apr 10;412(2):357-65. Moore PS, Chang Y. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer, 2010 Dec. 10(12): 878-889. Reisinger DM, Shiffer JD, Cognetta Jr. AB, Chang Y, and Moore PS. Lack of evidence for basal or squamous cell carcinoma infection with Merkel cell polyomavirus in immunocompetent patients with Merkel cell carcinoma, J Am Acad Dermatol, 2010 63(3):400-403. Houben R, Shuda M, Weinkam R, Schrama D, Feng H, Chang Y, Moore PS, Becker JC. Merkel cell polyomavirus infected Merkel cell carcinoma cells require expression of viral T antigens. J Virol, 2010 84:7064-7072. Tolstov YL, Arora R, Scudiere SC, Busam K, Chaudhary PM, Chang Y, Moore PS. Lack of evidence for direct involvement of Merkel cell polyomavirus (MCV) in chronic lymphocytic leukemia (CLL). Blood, 2010 115(23): 4973-4. Gjoerup O, Chang Y. Update on human polyomaviruses and cancer. Adv Cancer Res. 2010 106:1-51. Kim S, Li Z, Moore PS, Monaghan A, Chang Y, Nichols M, John B. A sensitive nonradioactive northern blot method to detect small RNAs. Nuc Acids Research, 2010 Apr 1;38(7):e98. Epub 2010 Jan 15. Moschos S, Chang Y, and Moore PS. Merkel Cell Polyomavirus: The Seventh Human Cancer Virus? The Melanoma Letter, 2009 Summer;27(2). Pastrana, DV, Tolstov YL, Becker JC, Moore PS, Chang Y, and Buck CB. Quantitation of human seroresponsiveness to Merkel cell polyomavirus. PLoS Pathog, 2009 Sept;5(9):e1000578 Kwun HJ, Guastafierro A, Shuda M, Meinke G, Bohm A, Moore PS, and Chang Y. The minimum replication origin of Merkel cell polyomavirus has a unique large T antigen loading architecture and requires small T antigen expression for optimal replication. J Virol, 2009 Dec;83(23):12118-28. Li, Z., Kim, S. W., Lin, Y., Moore, P. S., Chang, Y., & John, B. Characterization of viral and human RNAs smaller than canonical microRNAs. J Virol, 2009 Dec;83(24):12751-58. Busam K, Jungbluth AA, Rekhtman N, Coit D, Pulitzer M, Bini JM, Arora R, Hanson NC, Tassello JA, Frosina D, Moore PS, Chang Y. Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas. Am J Surg Path, 2009 Sep;33(9):1378-85. Tolstov Y, Pastrana D, Feng H, Becker J, Jenkins F, Moschos S, Chang Y, Buck C, Moore PS. Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int J Cancer, 2009 125:1250-1256. Shuda, M., R. Arora, H. J. Kwun, H. Feng, R. Sarid, M. T. Fernandez-Figueras, Y. Tolstov, O. Gjoerup, M. M. Mansukhani, S. H. Swerdlow, P. M. Chaudhary, J. M. Kirkwood, M. A. Nalesnik, J. A. Kant, L. M. Weiss, P. S. Moore, and Y. Chang. Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int J Cancer 2009 125:1243-9. Punj V, Matta H, Schamus S, Yang T, Chang Y, Chaudhary PM. Induction of CCL20 production by Kaposi sarcoma-associated herpesvirus; role of viral FLICE inhibitory protein K13-induced NF-kappaB activation. Blood, 2009 113(22):5660-8.