Arnold B. Rabson, MD

Arnold B. Rabson is Professor of Pediatrics, Pharmacology and Pathology and Laboratory Medicine. After completing his MD 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 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 HIV/AIDS and cancer. His laboratory elucidated the roles of the NF-kappaB transcription factors in the regulation of HIV. Dr. Rabson moved to Rutgers-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 the Cancer Institute for Basic Sciences. In 2002, he founded a division of Cancer Genomics and Molecular Oncology at the Cancer Institute and he became Deputy Director of Cancer Institute in 2005. He also served as Chair of the NIH Cancer Molecular Pathobiology Study Section. Dr. Rabson was appointed Interim Director of the Child Health Institute of New Jersey in 2007 and permanent Director in 2009. Under his direction, the Child Health Institute has established a vibrant research program and recruited outstanding scientists focused in the four major research areas of inflammation, immune and infectious diseases of childhood; neurodevelopment and autism; pediatric cancers and stem cells; and childhood obesity and metabolism.

Pathogenesis of human retroviral diseases including AIDS, and gene regulation in cancer and development.

Over the last four decades, the Rabson laboratory has made important research contributions in areas ranging from the regulation of gene expression in infections by the Human Immunodeficiency Virus (HIV) and the Human T Cell Leukemia/Lymphoma Virus type 1 (HTLV-1), to the roles of transcription factors in human cancers, to the identification of new proteins involved in the survival and growth of human cancer and stem cells. Major research accomplishments include:

• Discovery of the NF-kB transcription factors as a major regulator of HIV latency and reactivation.
• Discovery of alterations in the non-canonical NF-kB family in human T cell lymphomas.
• Characterization of the roles of the NF-kB transcription factors in prostate cancer progression.
• Identification of RNA stability as a major regulator of HTLV-1 gene expression.
• Characterization of PDCD2, a regulator of ribosome biogenesis, as a key regulator of cell cycle in development and cancer.

The Rabson laboratory has several areas of research focus spanning the molecular pathogenesis of human retroviral infections to the functions and roles of essential genes and gene regulatory pathways in stem cells, immune cells and cancer. 

• Mechanisms of pathogenesis of diseases caused by infection with HTLV-1.  HTLV-1 infection causes disease in 5-10% of infected individuals, and even asymptomatically infected people experience adverse health consequences and premature mortality. HTLV-1 associated diseases include a devastating malignancy of CD4 T cells, adult T cell leukemia/lymphoma (ATL) as well as a variety of chronic inflammatory diseases including a neurological disease called HTLV-Associated Myelopathy or Tropical Spastic Paraparesis (HAM/TSP).  The balance between active expression of HTLV-1 genes, such as the Tax transcriptional activator, and latent infection with little to no HTLV-1 gene expression likely plays a critical role in determining if HTLV- 1 infection is controlled by the immune response or progresses to clinical manifestations. Our laboratory has been studying the mechanisms of control of the integrated HTLV-1 provirus in infected cells. We have found that immune activation of infected T cells through the T cell receptor signaling-associated mechanisms activates expression of latent HTLV-1. Furthermore, this activation proceeds through a unique mechanism involving increased stability of the mRNA encoding Tax and a feedback activation of the HTLV-1 long terminal repeat (LTR) promoter (Figure 1, below). Current studies are addressing the mechanisms responsible for HTLV-1 mRNA stabilization and its consequences for viral and cellular gene expression and cellular proliferation.

• Mechanisms of HIV-associated neurological disease. In collaboration with the laboratories of Dr. Zhiping Pang (CHINJ) and Drs. Hart and Jeang (RU SAS), we are examining the infection of induced pluripotent stem cell (iPSC)-derived, human microglia by HIV. These studies are aimed at better understanding the pathogenic mechanisms responsible for HIV-associated neurocognitive disorders that affect large numbers of HIV-infected individuals, including many whose HIV infection is well-controlled by anti-retroviral drugs. We have developed a model system whereby we can reproducibly infect iPSC-derived, human microglia, resulting in a major induction of host cellular inflammatory responses. Furthermore, we have demonstrated that we can incorporate these infected microglial cells into iPSC-derived human cerebral organoids, providing a new model to examine perturbations in brain cell functions and interactions induced by HIV infection.  

• Functions of PDCD2 in development and disease. PDCD2 is an evolutionarily conserved, essential gene expressed at high levels in stem cells, cancer and development. Knockout of PDCD2 in mice leads to early lethality with a failure of blastocyst development and implantation, associated with a marked induction of the p53 pathway and cell cycle arrest (Figure 2, below). Studies from our lab, in collaboration with Drs. Steward (RU) and Pestov (Rowan U) have shown that PDCD2 interacts with ribosomal proteins and its loss leads to defects in ribosome biogenesis. Our current studies are focused on the mechanisms by which PDCD2 loss leads to altered cell phenotype and the consequences of PDCD2 expression for development, immune function and cancer.

• Regulation of cancer cell phenotype by epigenetic modifications. Our laboratory has developed a system to attenuate the malignant phenotype of colon cancer cells through induction of stable changes in histone modifications in chromatin induced by long-term treatment with histone deacetylase inhibitors. We are currently examining the mechanisms and consequences of this attenuation and its potential generalizability to other human cancer types, including pediatric cancers.

Duh EJ, Maury WJ, Folks TM, Fauci AS, Rabson AB. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974-8. PubMed Central PMCID: PMC297754.

Thakur S, Lin HC, Tseng WT, Kumar S, Bravo R, Foss F, Gélinas C, Rabson AB. Rearrangement and altered expression of the NFKB-2 gene in human cutaneous T-lymphoma cells. Oncogene. 1994 Aug;9(8):2335-44. PubMed PMID: 8036016. 

Swaims AY, Khani F, Zhang Y, Roberts AI, Devadas S, Shi Y, Rabson AB. Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells. Blood. 2010 Oct 21;116(16):2994-3003. PubMed Central PMCID: PMC2974607.

Granier CJ, Wang W, Tsang T, Steward R, Sabaawy HE, Bhaumik M, Rabson AB. Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest. Biol Open. 2014 Aug 22;3(9):821-31. PubMed Central ID: PMC4163659. 

Lin HC, Simon PJ, Ysla RM, Zeichner SL, Brewer G, Rabson AB. RNA stability regulates human T cell leukemia virus type 1 gene expression in chronically-infected CD4 T cells. Virology. 2017 Aug;508:7-17. PubMed Central PMCID: PMC5522752.

Krzyzanowska A, Haynes II RAH, Kovalovsky D, Lin H-C, Osorio L, Edelblum, KL, Corcoran LM, Rabson AB, Denzin LK, and Sant’Angelo DB.  Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis. Science Immunology, 2022, May 6; 7(71). PMID: 35522722