Research Overview
MOLECULAR IMMUNOLOGY OF LYMPHOCYTE PROLIFERATION AND APOPTOSIS
The primary objective of Dr. Lious research is to investigate the mechanism of gene regulation and signal transduction pathways that are crucial for shaping immune responses. A better understanding of the regulatory mechanisms of immune response will provide rationale and strategies for combating pathogenic infection as well as intervening unwanted immunopathological conditions such as chronic inflammation, autoimmune diseases, and graft rejection. Dr. Lious research has focused on the role of NF-kB/Rel transcription factors in the development and effector functions of immune cells. By using transgenic and knockout mouse models as well as molecular and cellular biology tools, her laboratory has demonstrated that c-Rel member of the NF-kB/Rel family is crucial for clonal expansion of lymphocytes in response to antigens. Subsequently the molecular mechanism has been defined to show that c-Rel is essential for lymphocyte proliferation and survival via the regulation of cell cycle regulators and pro-survival proteins. In addition to its pivotal role in lymphocytes, c-Rel is also essential for dendritic cell function as supported by the observation that dendritic cells lacking c-Rel are compromised for their ability to costimulate T cell responses. The physiological role of c-Rel in host defense and immune response has been further supported by studies using the c-Rel knockout mice. In general, the immune responses to antigenic and pathogenic challenge are compromised in the c-Rel knockout mice. On the other hand, deletion of c-Rel also proves to be beneficial for preventing hyperactive immune responses such as allergic inflammation and autoimmune disease. In addition, c-Rel suppression leads to tolerant environment in the immune system so that c-Rel knockout mice are able to accept allografts in several transplantation models. The future directions of Dr. Lious laboratory is to (i) identify c-Rel responsive genes in immune cells, (ii) develop specific c-Rel inhibitors, (iii) design strategies to dampen hyperactive immune responses or enhance host immune responses to pathogenic infection by modulating NF-kB activities in the immune system.
