UPCI Cancer Virology Lab Findings

mvcIn 2008, The Al Copeland Foundation (ACF) in philanthropic partnership with the University of Pittsburgh Cancer Institute (UPCI) embarked on the goal to cure Merkel Cell Carcinoma (MCC), a rare and aggressive form of skin cancer, that took the life of Al Copeland.  ACF has generously supported basic and translational research in the Cancer Virology Laboratory of Drs. Chang and Moore who first identified a new human cancer virus in MCC in 2008.  The unrestricted gift from ACF has enabled research that has moved MCC from an enigmatic entity with no known cause, with no clear diagnostic criteria, and with no effective treatment to a cancer for which we now know has a clear viral etiology.  Armed with this knowledge, progress has now been made on detection of infected individuals at risk for the cancer, testing for diagnosis, and most importantly dissecting out mechanisms for MCC development and finding directed, effective treatments.  The funds from  ACF has supported over 20 papers from the Chang-Moore Laboratory in prominent scientific journals reporting new findings including:

  • Development of diagnostic antibodies to detect the Merkel Cell Polyomavirus (MCV) in MCC
  • Establishment of blood tests to detect infection by MCV.
  • Identification of MCV viral proteins that directly transform healthy cells into cancer cells.
  • Identification of a drug effective for treating MCC in an MCC mouse model.
  • Elucidation of normal cellular pathways hijacked by MCV to promote tumor outgrowth.

Program Bio

The work of our group (jointly directed by Patrick Moore and Yuan Chang) has focused on human tumor viruses since the early 1990’s 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 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.

 Overview of Merkel Cell Virus Research

ChangThe Chang-Moore Laboratory in the Cancer Virology Program at the University of Pittsburgh Cancer Institute is responsible for discovering the viral causes of four different human cancers. In 1994, Chang-Moore lab identified and isolated Kaposi’s sarcoma-associated herpesvirus (KSHV) causing this epidemic cancer among HIV/AIDS patients. In addition to KS, KSHV causes primary effusion lymphoma (PEL) and most cases of multicentric Castleman’s disease (MCD). The Chang-Moore lab also developed a new technology (digital transcriptome subtraction, or DTS) for identifying human cancer viruses and in 2008 discovered Merkel cell polyomavirus (MCV) causing most Merkel cell carcinomas.  Drs. Moore and Chang are a husband and wife research team. Research in the Chang-Moore laboratory ranges from basic biological investigations into how cells become cancerous to epidemiologic/clinical research into the diagnosis, treatment and prevention of cancers caused by viruses.

Click here to read Dr. Chang’s bio