Dean Kedes Research Interests
The research in my laboratory focuses on a recently described human herpesvirus associated with Kaposi's sarcoma (KS), the most common AIDS-associated malignancy. This tumor has a complex pathology exhibiting mixed cellularity and abnormal angiogenesis and its genesis likely depends on viral replication within an immunologically impaired host. Epidemiological evidence has long implicated a transmissible agent in the etiology of Kaposi's sarcoma. Its high prevalence in homosexual men with AIDS and relative scarcity in their hemophiliac counterparts is one such suggestive observation. Kaposi's sarcoma-associated herpesvirus (KSHV) also termed human herpesvirus 8 (HHV-8) has been implicated by our work and that of others as the major etiologic agent in the development of this disease. In addition, KSHV, a gammaherpesvirus, is associated with a rare type of AIDS-associated body-cavity based B cell lymphoma (BCBL) also known as primary effusion lymphoma (PEL). These lymphomas have allowed the development of cell lines that, with appropriate stimuli, produce KSHV in culture.
Our investigations include two major areas. The first is the determination of the protein composition, spatial arrangement and assembly of both enveloped virions and subviral particles with special emphasis on the inner icosahedral capsid. This structure represents the completion of the first step in viral assembly and its formation is absolutely essential for replication. Our approaches include the coupling of classical molecular biology and biochemistry with electron microscopy (EM), immuno-EM and cryo-EM. The second is the isolation and characterization of viral genes and their protein products that are potentially involved in KSHV pathogenesis. In particular we are interested in the mechanisms underlying the virus's ability to evade host cell defenses, including apoptosis, the self-induced death of infected cells. We approach these aims by examining viral gene expression and viral-host protein interactions.
