Patrick S. Moore, MD, MPH
5117 Centre Avenue
We study 1) Kaposi’s sarcoma-associated herpesvirus (KSHV), the viral cause of Kaposi’s sarcoma, 2) Merkel cell polyomavirus (MCV), the viral cause of Merkel cell carcinoma and 3) methods to search for undiscovered human tumor viruses. Our recent studies on KSHV have shown that its major latency protein evades typical protein processing pathways to avoid provoking a cell-mediated immune response. We also have found that both KSHV and Epstein-Barr virus (EBV) undergo programmed frameshifting to generate novel latent proteins. This allows these viruses to increase their phenotypic diversity within tight biological constraints on their genome size. Surprisingly, these two distantly related viruses generate frameshifted proteins that are nearly identical to each other.
To search for new human tumor viruses, we have developed a technique called digital transcriptome subtraction (DTS) that allows us to sample tumor mRNA profiles for foreign transcripts. Unlike other new pathogen discovery techniques, DTS is quantitative so that we can essentially rule out infection if no foreign transcripts are found. We have successfully used DTS to measure KSHV transcription in infected cell lines, and we have demonstrated that an AIDS-related cancer, squamous cell conjunctival carcinoma, is unlikely to be caused by an exogenous infection.
Using DTS, we discovered Merkel cell polyomavirus (MCV), the likely cause of ~80% of Merkel cell carcinomas. MCV is the first polyomavirus to be found that is a likely cause of human cancer. We are characterizing the basic biology of this virus in host cell transformation, and we are searching for other diseases that may be related to MCV infection. We are developing monoclonal antibodies and serologic tests that will be useful diagnostic markers for infection. We have recently found a unique mutation in tumor-derived MCV that sheds light on tumor cell evolution and the fundamental mechanism for Merkel cell carcinogenesis. Recent studies by others have confirmed our initial findings for the role of MCV in MCC. Our laboratory has now discovered and characterized two of the seven known viral causes of human cancer. We are actively examining other cancers to search for additional human cancer viruses.
Dr. Moore conducts his research through the University of Pittsburgh Cancer Institute.
Kathleen Richards - Post Doctoral Associate
Erdong Cheng - Post Doctoral Associate