Abstract

This project focuses on a G protein-coupled receptor of HHV-8 which was found to be associated with Kaposi's sarcoma. It has recently been shown that this receptor functions via the phosphoinositide-inositol 1,4,5-triphosphate-calcium-protein kinase C signal transduction pathway, to induce cell proliferation and transformation; suggesting that HHV-8/GPCR may play a necessary, if not sufficient role in the abnormal proliferation exhibited by KS cells or lymphomatous B cells. The objectives of this research are to understand the biology of HHV-8 GPCR, and its role in the pathogenesis of KS.
Three specific aims are proposed. The first is to delineate the signaling mechanisms and modes of potential regulation of HHV-8 GPCR, and the biological consequences of HHV-8 GPCR expression in various cell types, such as cos, 293T, NIH 3T3, epithelial and B cells. The second is to discover high affinity, specific ligands for HHV-8 GPCR based on analogy to known chemokines. The third is to determine the roles of HHV-8 GPCR in disease pathogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA075918-05
Application #
6513130
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
1998-04-01
Project End
2004-06-30
Budget Start
2002-03-01
Budget End
2004-06-30
Support Year
5
Fiscal Year
2002
Total Cost
$349,642
Indirect Cost

  Institution

Name
Weill Medical College of Cornell University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Ashlock, Brittany M; Ma, Qi; Issac, Biju et al. (2014) Productively infected murine Kaposi's sarcoma-like tumors define new animal models for studying and targeting KSHV oncogenesis and replication. PLoS One 9:e87324
Mesri, Enrique A; Cavallin, Lucas E; Ashlock, Brittany M et al. (2013) Molecular studies and therapeutic targeting of Kaposi's sarcoma herpesvirus (KSHV/HHV-8) oncogenesis. Immunol Res 57:159-65
Ma, Qi; Cavallin, Lucas E; Leung, Howard J et al. (2013) A role for virally induced reactive oxygen species in Kaposi's sarcoma herpesvirus tumorigenesis. Antioxid Redox Signal 18:80-90
Mesri, Enrique A; Cesarman, Ethel; Boshoff, Chris (2010) Kaposi's sarcoma and its associated herpesvirus. Nat Rev Cancer 10:707-19
Sarosiek, Kristopher A; Cavallin, Lucas E; Bhatt, Shruti et al. (2010) Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma. Proc Natl Acad Sci U S A 107:13069-74
Ma, Qi; Cavallin, Lucas E; Yan, Bin et al. (2009) Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma. Proc Natl Acad Sci U S A 106:8683-8
Muratori, Claudia; Cavallin, Lucas E; Kratzel, Kirsten et al. (2009) Massive secretion by T cells is caused by HIV Nef in infected cells and by Nef transfer to bystander cells. Cell Host Microbe 6:218-30
Mutlu, Agata D'Agostino; Cavallin, Lucas E; Vincent, Loic et al. (2007) In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: a cell and animal model of virally induced Kaposi's sarcoma. Cancer Cell 11:245-58
Cesarman, E; Mesri, E A (2007) Kaposi sarcoma-associated herpesvirus and other viruses in human lymphomagenesis. Curr Top Microbiol Immunol 312:263-87
Ho, H H; Du, D; Gershengorn, M C (1999) The N terminus of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor is necessary for high affinity chemokine binding but not for constitutive activity. J Biol Chem 274:31327-32

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