Dean H. Kedes
Primary AppointmentProfessor, Microbiology, Immunology, and Cancer Biology
- BS, Biology, Stanford University
- MD, Yale School of Medicine
- PhD, Molecular Biophysics and Biochemistry , Yale University
Human Herpes virus associated with malignancy, including Kaposi's Sarcoma
Kaposi's sarcoma (KS) remains one of the two most common AIDS-associated malignancies and is caused by the human herpesvirus, KSHV, first discovered in 1994. Nevertheless, many details of KSHV infection and pathogenesis remain unclear. A rare type of B cell lymphoma (PEL) also arising from KSHV infection, has allowed the development of cell lines that produce KSHV in culture. These lines, along with a manipulable bacterial artificial chromosome of the approximately 165kbp viral genome, have allowed the study of viral structure, assembly, gene expression and pathogenesis. Examining both KSHV and its close non-human primate pathogen, rhesus monkey rhadinovirus (RRV), we have focused on the following four major areas:
1. Viral gene culprits: Isolation and characterization of viral genes and their protein products involved in KSHV pathogenesis. In particular we are interested in the mechanisms underlying a) the activation of cellular signaling during viral entry and b) the pathway of viral egress, including the affects of viral gene products on the cytoskeleton. 2. Viral structure and proteomics: Determination of the protein composition, spatial arrangement and assembly of viral and subviral particles. Our approaches include the coupling of classical molecular biology and virology with biochemistry, electron microscopy (EM), and, through collaborations with colleagues that include Pew Scholar, Z. Hong Zhu (UCLA), immuno-EM and cryo-EM. 3. Viral tropism in patients: Identification of the cell types initially infected during primary transmission of KSHV in humans.
4. Investigations into the structural connection between viral and human genomes during latent (chronic) infection, in a collaborative effort with the laboratory of Mitchell Smith and using sub-nanometer microscopy.