Office: SRB 2
Ph.D., University of North Carolina, Chapel Hill
Postdoctoral Fellow: Rockefeller University (93-94), MIT (94-96)
Research in the Beg laboratory is focused on the following three areas:
1) T cell activation pathways. T lymphocytes play a critically important role in the immune response to infectious agents and cancer. Working together, T cells and dendritic cells (DCs) are crucial for initiating an immune response. Antigens displayed on the surface of DCs are recognized by the T cell receptor present on T cells to initiate T cell activation. Focusing on the NF-kappa B family of transcription factors, we are investigating the specific role played by different NF-kappa B subunits in T cell activation. Our studies utilize mice in which different subunits of NK-kappa B subunits or potential activators of NF-kappa B such as PKC-theta/alpha have been knocked-out. We are investigating the role played by the NF-kappa B pathway both in early stages of T cell activation as well as in effector functions important for allo-reactivity/GVHD and anti-tumor responses.
2) Regulation of tumor immune surveillance by NF-kappa B. NF-kappa B is activated in many cancer types and functions as an important mediator of tumor-associated inflammation and metastasis. The presence of T cells in tumors can be associated with immune surveillance functions as well as improved patient survival. We are investigating whether in addition to known pro-tumor functions, NF-kappa B activity in cancer cells is also associated with T cell-mediated anti-tumor responses. This project specifically focuses on NF-kappa B function in tumor cells, unlike the above project aimed at studying NF-kappa B function in T cells. Our findings indicate that tumor NF-kappa B activity is strongly associated with T cell infiltration and anti-tumor immune responses. The goals of this study are to define fundamental mechanisms and develop pharmacological approaches to boost NF-kappa B immune surveillance functions in tumors.
3) Modulating the immune response to adenovirus vectors by intracellular adjuvants. Adenovirus vector (AdV) vaccines have received considerable attention because of their relative safety and ability to induce immune responses. In previous studies, we identified key roles of NF-kappa B and IRF transcription factors in immune responses to viruses. We are currently investigating whether the vaccine potential of AdV can be significantly enhanced through expression of these molecules i.e., intracellular adjuvants. If successful, these studies can have a major impact on the future design of potent AdV and potentially non-AdV vaccines against infectious agents and cancer.
Recent Journal Articles
Honors and Award
Search for publications by: Beg AA
This search will be conducted at the US National Library of Medicine (NLM) and PubMed.
1) Valenzuela JO, Iclozan C, Hossain MS, Prlic M, Hopewell E, Bronk CC, Wang J, Celis E, Engelman RW, Blazar BR, Bevan MJ, Waller EK, Yu XZ, Beg AA. PKC-theta is required for alloreactivity and GVHD but not for immune responses toward leukemia and infection in mice. J Clin Invest. 2009 Dec; 119(12):3774-86.
2)Wang J, Basagoudanavar SH, Wang X, Hopewell E, Albrecht R, García-Sastre A, Balachandran, S, Beg AA. NF-kappa B RelA subunit is crucial for early IFN-beta expression and resistance to RNA virus replication. J Immunol. 2010 Aug 1; 185(3):1720-9.
3) Ruan Q, Kameswaran V, Zhang Y, Zheng S, Sun J, Wang J, DeVirgiliis J, Liou HC, Beg AA, Chen YH. The Th17 immune response is controlled by the Rel-ROR?-ROR? T transcriptional axis. J Exp Med. 2011 Oct 24; 208(11):2321-33.
4)Balachandran S, Beg AA. Defining emerging roles for NF-?B in antivirus responses:revisiting the interferon-ß enhanceosome paradigm. PLoS Pathog. 2011 Oct; 7(10):e1002165.
5) Hopewell EL, Bronk CC, Massengill M, Engelman RW, Beg AA. IKKß-induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector. Eur J Immunol. 2012 Mar; 42(3):681-7.