Professor, Microbiology-Immunology; Feinberg School of Medicine
Cancer Cell Biology,Hematologic Malignancies
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Research in the Longnecker laboratory focuses on herpes simplex virus (HSV) and Epstein-Barr virus (EBV). Both of these viruses, which are members of the herpesvirus family, typically cause self-limiting disease within the human population but both can be associated with serious complications. The most notable disease associated with EBV infection is infectious mononucleosis which is a self-limiting lymphoproliferative disease that occurs in normal adolescents upon primary infection. Children are normally able to resolve primary EBV infection with few or no symptoms. By the age of 25 most individuals are EBV seropositive. EBV is associated with variety of hematopoietic cancers such as African Burkitt's lymphoma, Hodgkin's and adult T-cell leukemia. EBV-associated lymphoproliferative disease occurs in individuals with congenital or acquired cellular immune deficiencies. The two notable epithelial diseases associated with EBV infection are nasopharyngeal cancer, a malignancy endemic to southern China; and oral hairy leukoplakia, an epithelial hyperplasia of the lingual squamous epithelium in AIDS patients. Similar to EBV, HSV latent infections are very common in humans. HSV typically does not cause severe disease but is associated with localized mucocutaneous lesions, but in some cases can cause meningitis and encephalitis. The Longnecker laboratory focuses on several aspects of EBV and HSV pathogenesis. First, the laboratory is interested in transformation. Specifically, research is being conducted to understand the molecular basis of the ability of EBV to transform and provide anti-apoptotic signals to primary B lymphocytes. These studies are particularly important since EBV is associated with a variety of malignancies in the human host. The laboratory is currently screening selective inhibitors that may be beneficial in EBV-associated cancers such as Hodgkin's lymphoma and proliferative disorders that occur in HIV/AIDS and transplant patients. Second, the laboratory is interested in understanding the ability of the virus to persist and remain latent in human host. In this regard, the laboratory is developing animal models for EBV latent infections. Finally, the laboratory is investigating the function of herpesvirus (HSV and EBV) encoded proteins that are important in herpesvirus infection and the interactions required with cellular receptors required for infection. Specifically viral genes important for virus binding, entry, and maturation from susceptible cells and being studied. Ultimately, studies by the Longnecker may provide insight for the development of novel therapeutics for the treatment of herpesvirus infections in humans and better understanding of the herpesvirus life cycle in the human host.