Dean H. Kedes, MD, PhD
Graduate School: Yale University
Primary Appointment: Associate Professor, Medicine, Infectious Diseases and International Health
Human Herpes virus Associated with Kaposi's Sarcoma
Email Address: email@example.com
Pathogenesis of Kaposi’s Sarcoma-Associated Herpesvirus: using
approaches from virology, infectious diseases, immunology, and both
cell and molecular biology.
Kaposi's sarcoma (KS), the most common AIDS-associated malignancy, is caused by the human herpesvirus, KSHV. Nevertheless, the 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 have allowed the study of viral structure, assembly, gene expression and pathogenesis. Our investigations involve four major areas:
- 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 the virus’s ability to evade host cell defenses as well as to activate and potentially exploit host signal transduction pathways.
- 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), immuno-EM and cryo-EM.
- Animal models of viral infection: Development of a transgenic and xenograft (humanized) mouse models of KSHV infection that will allow us to monitor the cellular immune response to viral proteins, taking advantage of a transgenic mice expressing human HLA molecules.
- Viral tropism in patients: Identification of the cell types initially infected during primary transmission of KSHV in humans, including understanding better the intracellular milieu favoring latent versus lytic stages of the viral life cycle.
Borah S, Nichols LA, Hassman LM, Kedes DH, Steitz JA. Tracking expression and subcellular localization of RNA and protein species using high-throughput single cell imaging flow cytometry. RNA. 2012 Aug;18(8):1573-9. doi: 10.1261/rna.033126.112. Epub 2012 Jun 28.
Woodson EN, Kedes DH. Distinct roles for extracellular signal-regulated kinase 1 (ERK1) and ERK2 in the structure and production of a primate gammaherpesvirus. J Virol. 2012 Sep;86(18):9721-36. doi: 10.1128/JVI.00695-12. Epub 2012 Jun 27.
Nichols LA, Adang LA, Kedes DH. Rapamycin blocks production of KSHV/HHV8: insights into the anti-tumor activity of an immunosuppressant drug. PLoS One. 2011 Jan 14;6(1):e14535. doi: 10.1371/journal.pone.0014535.
Hassman LM, Ellison TJ, Kedes DH. KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation. J Clin Invest. 2011 Feb;121(2):752-68. doi: 10.1172/JCI44185. Epub 2011 Jan 18.
Deng B, O'Connor CM, Kedes DH, Zhou ZH. Cryo-electron tomography of Kaposi's sarcoma-associated herpesvirus capsids reveals dynamic scaffolding structures essential to capsid assembly and maturation. J Struct Biol. 2008 Mar;161(3):419-27. doi: 10.1016/j.jsb.2007.10.016. Epub 2007 Nov 17.
Adang LA, Tomescu C, Law WK, Kedes DH. Intracellular Kaposi's sarcoma-associated herpesvirus load determines early loss of immune synapse components. J Virol. 2007 May;81(10):5079-90. Epub 2007 Feb 28.
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