Arnold B. Rabson M.D.
Professor and Director
UMDNJ-Robet Wood Johnson Medical School
Child Health Institute of NJ
89 French Street, 3rd floor, room 3211
New Brunswick, NJ 08901
Dr. Rabson is Professor of Molecular Genetics, Microbiology, and Immunology, and of Pathology and Laboratory Medicine. After completing his M.D. at Brown University, Dr. Rabson moved to Harvard Medical School, where he pursued residency training in anatomic pathology at the Brigham and Women's Hospital,(including a stint) in pediatric pathology at Boston Children's Hospital. He then moved to the National Institutes of Health where he studied the molecular biology and pathogenesis of retroviral diseases including HIV/AIDS and cancer. His laboratory elucidated the roles of the NF-kappaB transcription factors in the regulation of HIV infection and was also the first to demonstrate infection of placental cells by HIV, thus identifying important mechanisms of infection in pediatric AIDS. Dr. Rabson moved to UMDNJ-Robert Wood Johnson Medical School in 1990 as a Resident member of the Center for Advanced Biotechnology and Medicine, where he continued his research on the molecular pathogenesis of human retroviral infections and also discovered roles for the NF-kappaB pathway in the pathogenesis of human lymphomas. He was the founding leader of The Cancer Institute of New Jersey's Transcriptional Regulation and Oncogenesis Program, and in 1997, he became Associate Director of CINJ for Basic Sciences. In 2002, he was asked to found a division of Cancer Genomics and Molecular Oncology at CINJ, and he became Deputy Director of CINJ in 2005. He is also the Chair of the NIH Cancer Molecular Pathobiology Study Section. Thus, Dr. Rabson brings extensive research and scientific administrative experience to his new role as Director of the Child Health Institute of New Jersey.
Our laboratory is interested in the molecular basis of human disease pathogenesis. Our research focuses on gene regulation in human cancer and on the regulation and on the pathogenesis of human retroviral infections.
Several projects in the lab focus on the roles of the NF-kB family of transcription factors in human diseases, particularly cancer and immune diseases. The NF-kB transcription factors play critical roles in all immune and inflammatory responses and are central in the pathogenesis of many human diseases ranging from inflammatory diseases such as asthma and autoimmune disorders, to metabolic, proliferative and degenerative diseases. Our laboratory has been studying the roles of NF-kB in the development of human lymphomas for a number of years. NF-kB plays an important role in the control of normal immune activation and T-cell proliferation. Previous studies from our laboratory identified alterations of the NF-kB transcription factor in a subset of T-cell lymphomas. We demonstrated that the NF-kB2 protein is truncated in patients with cutaneous T cell lymphoma (CTCL), a malignant disease of T lymphocytes involving the skin, lymph nodes, and blood. Alterations of this gene result in constitutive activation of the NF-kB transcription factor, which may lead to unrestrained T-cell proliferation and the eventual development of malignancy. Studies in the laboratory are aimed at understanding the mechanisms by which alterations of the NF-kB2 gene leads to uncontrolled T cell proliferation and cancer. We have shown that NF-kB2 alterations result in both loss of an "IkB-like" inhibitory function associated with the full-length NF-kB2 molecule as well as a gain of function of the truncated, tumor-associated molecules in enhancing T-cell viability and proliferation, as well as the expression of potent anti-apoptotic genes. We are also continuing to pursue collaborative studies with Dr. Gélinas at the CABM to further understand the roles of various NF-kB and IkB proteins in lymphomas. Further experiments are also examining the functions of the Bcl-3 protein, an IkB-like protein that cooperates with NF-kB2 proteins to increase the expression of NF-kB target genes. Bcl-3 is a protooncogene whose expression is deregulated in a subset of chronic lymphocytic leukemias. We have shown that Bcl-3 mediated transcription is regulated by immune activation stimuli, thus Bcl-3 overexpression may activate genes involved in immune cell survival and proliferation, thus contributing to lymphomagenesis.
In collaborative translational research studies with Drs. Roger Strair and Daniel Medina at the The Cancer Institute of New Jersey, we have also examined the potential utility of NF-kB as a target for therapy of acute leukemias and have been able to show inhibition of NF-kBin leukemic blasts following treatment of patients therapy with available anti-inflammatory agents.
Our laboratory also studies the molecular biology and pathogenesis of the human retroviruses, HTLV-1 and HIV. HTLV-1 infects human T cells. HTLV-1 infection often occurs in infants and young children. Infected individuals either remain asymptomatic, or develop either aggressive T-cell leukemias and lymphomas (ATL) or a central nervous system disease, HTLV-associated myelopathy (HAM/TSP). The variable outcome of HTLV-1 infection suggests that host factors such as the host immune response or intracellular factors that control HTLV-1 gene expression may contribute to the pathogenesis of HTLV-1 infection. Our laboratory identified models of HTLV-1 latent infection of human T cells, and showed that HTLV-1 gene expression can be induced by treatment of the cells with immune activation stimuli. This suggests that immune system activation may directly regulate the replication of HTLV-1and expression of viral transforming proteins, possibly contributing to the pathogenesis of HTLV-1-associated disease. We have also shown that immune activation of cells containing the HTLV-1 Tax transactivator gene is sufficient to induce oncogenic Tax expression leading to T-cell immortalization, modeling early steps in HTLV-induced leukemia/lymphoma. The cellular mechanisms responsible for HTLV-1 activation and viral pathogenesis are currently under study. Our lab is also continuing studies of the roles of cellular transcription factors in the regulation of HIV gene expression. We identified the critical role of NF-kB in activating latent HIV and demonstrated the effects of Sp1 on viral replication. Studies of the replication of HIV LTR promoter mutants are on-going. We are also studying the efficacy of novel anti-HIV therapeutic agents.