Robert Wood Johnson Medical School
Dept of Pharmacology
The Child Health Institute of NJ
89 French Street, Room 3210
New Brunswick, NJ 08903
Gene regulation in cancer, human retroviral infections
Our laboratory is interested in the roles of altered gene expression in human cancer and in human retroviral infections. One set of projects focuses on the controls of gene expression of HIV and of the human T cell leukemia virus type 1 (HTLV-1) in infected T cells. We have previously demonstrated the important roles of the NF-kappaB transcription factors in the activation of latent HIV infection. More recently, we identified models of latent HTLV-1 infection and have shown that immune activation stimuli will induce HTLV gene expression. This suggests important models for the activation of HTLV during disease pathogenesis. Other experiments in the laboratory have focused on the roles of the NF-kappaB transcription factors in human cancer. We have identified mutations of the NF-kB-2 gene that occur in 5-30% of human cutaneous T cell lymphomas and are associated with altered transcriptional regulation leading to increased T cell activation. proliferation, and survival, that may contribute to T cell lymphomagenesis. We have also observed very high levels of constitutive NF-kB activation in androgen-independent human prostate cancer cell lines and are studying the responsible mechanisms as well as the consequences for prostate cancer progression.