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Cancer Virus Discovery investigators

Yuan Chang, MD
Contact:
Hillman Cancer Center
5117 Centre Ave Suite 1.8
Pittsburgh PA
Research Interests and Keywords:
  • Tumor viruses
  • Kaposi's sarcoma associated herpesvirus (KSHV)
  • Merkel cell polyomavirus (MCV)
  • digital transcriptome subtraction
  • tumor virus discovery
Summary
The work of our group (jointly directed by Patrick Moore and Yuan Chang) has focused on human tumor viruses since the early 1990s when we identified Kaposi's sarcoma associated herpesvirus (KSHV/HHV8) and showed that this virus was causally associated with Kaposi's sarcoma, the most common AIDS-related cancer in the United States and the most common malignancy in parts of Africa. We sequenced the KSHV genome, developed serologic assays, determined its prevalence in human populations, and characterized many of its critical viral oncoproteins. We have continued to study virus-host cell interactions in the context of dysregulation of pro-proliferative and anti-apoptotic pathways. We recently identified the seventh human tumor virus, Merkel cell polyomavirus (MCV), from a Merkel cell carcinoma (MCC). We characterized the transcriptional products of MCV and described the early region viral T antigen oncoproteins. Our work has established that MCV causes ~80% of MCC: we determined that the virus is clonally integrated in MCC tumor cells; that human tumor-associated Large T (LT) antigens contain signature truncation mutations; that T antigen proteins are expressed in MCC tumor cells by novel antibodies we developed; and we are the first laboratory to show rodent cell transformation by MCV sT antigen but not the LT antigen. We have identified several novel cellular interactors for MCV T antigens that open new avenues of investigating critical oncogenic signaling pathways. We have focused on many aspects of cancer etiology as modeled through oncogenic tumor viruses.
Patrick Moore, MD, MPH
Contact:
Hillman Cancer Center
Lab 1.8
Pittsburgh PA
Research Interests and Keywords:
  • Human tumor virology (KSHV, MCV and digital transcriptome subtraction)
James Pipas, PhD
Contact:
559B Crawford Hall
4249 Fifth Avenue
Pittsburgh PA
Phone: 412-624-4691
Research Interests and Keywords:
  • Simian virus 40 (SV40)
  • T antigen
  • tumorigenesis
Summary
Simian virus 40 (SV40) belongs to a small collection of viruses that induce tumors. We utilize SV40 as a model system for understanding the molecular events that drive tumorigenesis. Our studies focus on the virus-encoded master regulatory protein, large T antigen. Large T antigen controls several aspects of viral infection including DNA replication, transcription and virion assembly. In addition, T antigen is necessary and, in most cases, sufficient for SV40-mediated tumorigenesis. T antigen induces tumors in rodents and the neoplastic transformation of cells in culture by binding to key cellular proteins that regulate proliferation and survival, and altering their activities. Our basic strategy is to use a combination of genetics and proteomics to identify cellular targets of T antigen and then to use molecular biology and mouse model approaches to understand how these actions contribute to tumorigenesis.
Joseph Newsome, DVM
Contact:
1050 South TE DLAR
Starzl Biomedical Science Tower 200 Lothrop Street
Pittsburgh PA
Phone: 412-648-8950
Research Interests and Keywords:
  • Immunopathology
  • vaccinology
  • dermatopathology
  • papillomavirus
  • infectious disease animal modeling
Massahiro Shuda
Contact:
UPCI Research Pavilion at Hillman Cancer Center, 1.9
5117 Centre Avenue
Pittsburgh PA
Phone: 412-623-7733
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