Virol & Micro: Marriott
Baylor College of Medicine
Houston, TX, US
Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas, United States


Advanced Training from National Institutes Of Health
Ph.D. from Kansas State University
B.S. from Iowa State University Of Science & Technology

Professional Interests

  • Viral transformation and transcription control

Professional Statement

Viral Transformation and Transcription Control

Human T-cell leukemia virus (HTLV-I) is the etiologic agent of at least two human diseases, adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). The viral genome encodes a regulatory protein, Tax, which functions as a transcriptional transactivator of viral and cellular gene expression, and is the transforming protein of HTLV-I. The primary interest of my laboratory is to use Tax as a model system to understand cellular transformation. Our efforts are focused on:

Defining the mechanism of Tax transactivation of the HTLV-I promoter located in the long terminal repeat (LTR). Tax does not bind DNA directly; however, it can associate with the cellular transcription factors including CREB, NF-kB, and SRF. We are investigating the molecular mechanisms of Tax transactivation of viral and cellular promoters with specific interest in the effect of Tax on chromatin remodeling through recruitment of histone acetyltransferases.

Determining the effect of Tax on cell cycle progression and DNA replication/repair. The ability of Tax to transform cells is thought to depend on its ability to activate expression of a select group of cellular genes. Tax activates transcription of the proliferating cell nuclear antigen (PCNA) promoter. PCNA is an essential co-factor of DNA polymerase delta and thus is intimately linked to DNA replication and repair. We have demonstrated that Tax can inhibit the cell’s ability to repair DNA damage. In cells expressing Tax, we propose that PCNA overexpression inhibits DNA repair and stimulates DNA replication, thus fixing mutations in the genome. Supporting this model, Tax stimulates cell cycle progression even in the presence of DNA damage. We have mapped this cell cycle defect to the G1/S checkpoint. The disruption of cellular mechanisms that coordinate DNA replication and repair may allow accumulation of DNA damage and thus play an important role in transformation