Dean H. Kedes

Education

  • MD, Yale School of Medicine
  • PhD, Yale University

Primary Appointment

  • Associate Professor, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

Human Herpes virus associated with Kaposi's Sarcoma

Research Description



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:

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 the virus’s ability to evade host cell defenses as well as to activate and potentially exploit host signal transduction pathways.

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), immuno-EM and cryo-EM.

3. 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. 

4. 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.

Selected Publications

  • Woodson E, Anderson M, Loftus M, Kedes D. Progressive Accumulation of Activated ERK2 within Highly Stable ORF45-Containing Nuclear Complexes Promotes Lytic Gammaherpesvirus Infection. PLoS pathogens. 2014;10(4): e1004066. PMID: 24722398 | PMCID: PMC3983062
  • Borah S, Nichols L, Hassman L, Kedes D, Steitz J. Tracking expression and subcellular localization of RNA and protein species using high-throughput single cell imaging flow cytometry. RNA (New York, N.Y.). 2012;18(8): 1573-9. PMID: 22745225 | PMCID: PMC3404377
  • Woodson E, Kedes D. Distinct roles for extracellular signal-regulated kinase 1 (ERK1) and ERK2 in the structure and production of a primate gammaherpesvirus. Journal of virology. 2012;86(18): 9721-36. PMID: 22740395 | PMCID: PMC3446570
  • Hassman L, Ellison T, Kedes D. KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation. The Journal of clinical investigation. 2011;121(2): 752-68. PMID: 21245574 | PMCID: PMC3026728
  • Nichols L, Adang L, Kedes D. Rapamycin blocks production of KSHV/HHV8: insights into the anti-tumor activity of an immunosuppressant drug. PloS one. 2011;6(1): e14535. PMID: 21264294 | PMCID: PMC3021514
  • Deng B, O'Connor C, Kedes D, Zhou Z. Cryo-electron tomography of Kaposi's sarcoma-associated herpesvirus capsids reveals dynamic scaffolding structures essential to capsid assembly and maturation. Journal of structural biology. 2008;161(3): 419-27. PMID: 18164626 | PMCID: PMC2692512
  • Adang L, Tomescu C, Law W, Kedes D. Intracellular Kaposi's sarcoma-associated herpesvirus load determines early loss of immune synapse components. Journal of virology. 2007;81(10): 5079-90. PMID: 17329329 | PMCID: PMC1900224
  • Adang L, Parsons C, Kedes D. Asynchronous progression through the lytic cascade and variations in intracellular viral loads revealed by high-throughput single-cell analysis of Kaposi's sarcoma-associated herpesvirus infection. Journal of virology. 2006;80(20): 10073-82. PMID: 17005685 | PMCID: PMC1617294
  • O'Connor C, Kedes D. Mass spectrometric analyses of purified rhesus monkey rhadinovirus reveal 33 virion-associated proteins. Journal of virology. 2006;80(3): 1574-83. PMID: 16415032 | PMCID: PMC1346966
  • O'Connor C, Kedes D. Rhesus monkey rhadinovirus: a model for the study of KSHV. Current topics in microbiology and immunology. 2006;312 43-69. PMID: 17089793
  • Parsons C, Adang L, Overdevest J, O'Connor C, Taylor J, Camerini D, Kedes D. KSHV targets multiple leukocyte lineages during long-term productive infection in NOD/SCID mice. The Journal of clinical investigation. 2006;116(7): 1963-73. PMID: 16794734 | PMCID: PMC1481659