Associate Physician
Brigham and Women's Hospital

kkaye@rics.bwh.harvard.edu

Our laboratory investigates Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). KSHV has a causative role in Kaposi's sarcoma, primary effusion lymphomas and multicentric Castleman's disease, an aggressive lymphoproliferative disorder. KSHV infection is predominantly latent in tumors and tumor cell lines. In latently infected cells, KSHV persists as an extrachromosomal, multiple copy plasmid (episome).

The latency-associated nuclear antigen (LANA) mediates KSHV episome persistence by permitting viral DNA replication and then tethering KSHV episomes to mitotic chromosomes to ensure their efficient segregation to progeny nuclei. We are currently investigating the molecular mechanisms underlying these functions. An understanding of these mechanisms may allow the development of strategies that interrupt LANA function and lead to prevention and treatment of KSHV associated tumors.

Ballestas ME, Chatis PA, Kaye KM. Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science. 1999 Apr 23;284(5414):641-4. [abstract]

Ballestas ME, Kaye KM. Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mediates episome persistence through cis-acting terminal repeat (TR) sequence and specifically binds TR DNA. J Virol. 2001 Apr;75(7):3250-8. [abstract]

Li H, Komatsu T, Dezube BJ, Kaye KM. The Kaposi's sarcoma-associated herpesvirus K12 transcript from a primary effusion lymphoma contains complex repeat elements, is spliced, and initiates from a novel promoter. J Virol. 2002 Dec;76(23):11880-8. J Virol. 2002;76:11880-11888. [abstract]>

Barbera A, Ballestas ME, Kaye KM. The Kaposi’s sarcoma-associated herpesvirus latency-associated nuclear antigen 1 N-terminus is essential for chromosome association, DNA replication, and episome persistence. J Virol. 2004 Jan;78(1):294-301. [abstract]

Barbera AJ, Chodaparambil JV, Kelley-Clarke B, Joukov V, Walter JC, Luger K, Kaye KM. The nucleosomal surface as a docking station for Kaposi’s sarcoma herpesvirus LANA. Science. 2006 Feb 10;311(5762):856-61. [abstract]