{"id":2,"date":"2017-11-08T16:53:11","date_gmt":"2017-11-08T16:53:11","guid":{"rendered":"https:\/\/fs.wp.odu.edu\/pkraj\/?page_id=2"},"modified":"2017-12-11T23:25:49","modified_gmt":"2017-12-11T23:25:49","slug":"sample-page","status":"publish","type":"page","link":"https:\/\/fs.wp.odu.edu\/pkraj\/","title":{"rendered":"Research Interests"},"content":{"rendered":"
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Kraj Lab People 2016<\/p><\/div>\n

The laboratory of Dr. Kraj studies the development and function of CD4+<\/sup> T lymphocytes and mechanisms of immunological tolerance. A number of cellular, molecular and bioinformatics tools are used. The goal of this research is to uncover how tolerance mechanisms could be modulated to augment immune responses in cancer and control these responses in autoimmunity.<\/p>\n

The discovery of regulatory T cells (TR<\/sub>) expressing transcription factor Foxp3 brought a new paradigm that immune tolerance is established and maintained by active suppression. TR<\/sub> cells maintain immunological tolerance; sustain homeostasis of the immune system and control antigenic responses of effector T cells. However, these cells are also responsible for suppressing immune responses to tumor cells allowing cancer to grow. Dr. Kraj investigates how thymic development of TR<\/sub> cells is regulated, what factors control maintenance and generation of TR<\/sub> cells in the periphery, and what is the mechanism of TR<\/sub> suppressor function.<\/p>\n

To discriminate TR<\/sub> cells, a reporter mouse was produced that expresses green fluorescent protein controlled by the Foxp3 regulatory sequences and was used to show that the peripheral population of TR<\/sub> cells is heterogeneous and TR<\/sub> subsets differentially respond to antigenic stimulation with conventional and tumor-associated antigens. Comparison of the global gene expression profiles of conventional CD4+<\/sup> T cells and TR<\/sub> cells identified genes that are TR<\/sub> cell-specific and that could be targeted to modulate TR<\/sub> cell function.<\/p>\n

One of the identified genes, which controls TR<\/sub> cell suppressor function, is connexin 43, a gap junction protein. By deleting connexin 43 in T cells, Dr. Kraj\u2019s laboratory found that it controls Foxp3 expression and thymic generation of TR<\/sub> cells. Recently, we found that compromised suppression mediated by TR<\/sub> cells was associated with decreased expression of Cx43 in NOD mice, a mouse model of diabetes. The suppressor function of TR<\/sub> cells can be corrected in vitro<\/em>, even in T cells isolated from mice with advanced diabetes, by a novel reagent, which facilitates gap junction formation.<\/p>\n

The laboratory is also investigating how Bone Morphogenic Protein Receptor 1\u03b1 (BMPR1\u03b1) signaling controls functions of conventional and TR<\/sub> cells. BMPR1\u03b1 (Alk-3), expressed by activated effector and TR<\/sub> cells modulates functions of both cell types. Bone Morphogenic Proteins (BMPs) belong to the TGF-\u03b2 family of cytokines, which also includes TGF-\u03b2 and activins. BMPs play crucial roles in embryonic development, tissue differentiation and homeostasis, and development of cancer. It was demonstrated that BMPs and activins synergize with TGF-\u03b2 to regulate thymic T cell development, and maintain TR<\/sub> cells and peripheral tolerance, but the precise mechanism of their function is not known. BMPR1\u03b1 ligands, BMPs, are produced by multiple tumors and we hypothesized that BMPR1\u03b1 augments suppressor function of existing TR<\/sub> cells, promotes conversion of activated conventional CD4+<\/sup> T cells into adaptive TR<\/sub> cells and modulates balance between the subsets of effector CD4+<\/sup> T cells. We have recently shown BMPR1\u03b1 gene deficient CD4+<\/sup> T cells. Mice where BMPR1\u03b1 is deleted in T cells (BMPR1\u03b1T-<\/sup> mice) had a decreased proportion of TR<\/sub> cells and activated T cells did not produce adaptive TR<\/sub> cells but preferentially to develop into pro-inflammatory Th17 cells. Moreover, B16 melanoma tumors grew smaller in BMPR1\u03b1T-<\/sup> mice and tumors had very few infiltrating TR<\/sub> cells and a higher proportion of CD8+<\/sup> T cells.<\/p>\n","protected":false},"excerpt":{"rendered":"

The laboratory of Dr. Kraj studies the development and function of CD4+ T lymphocytes and mechanisms of immunological tolerance. A number of cellular, molecular and bioinformatics tools are used. The goal of this research is to uncover how tolerance mechanisms… Continue Reading →<\/a><\/p>\n","protected":false},"author":8511,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"open","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/fs.wp.odu.edu\/pkraj\/wp-json\/wp\/v2\/pages\/2"}],"collection":[{"href":"https:\/\/fs.wp.odu.edu\/pkraj\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/fs.wp.odu.edu\/pkraj\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/fs.wp.odu.edu\/pkraj\/wp-json\/wp\/v2\/users\/8511"}],"replies":[{"embeddable":true,"href":"https:\/\/fs.wp.odu.edu\/pkraj\/wp-json\/wp\/v2\/comments?post=2"}],"version-history":[{"count":2,"href":"https:\/\/fs.wp.odu.edu\/pkraj\/wp-json\/wp\/v2\/pages\/2\/revisions"}],"predecessor-version":[{"id":17,"href":"https:\/\/fs.wp.odu.edu\/pkraj\/wp-json\/wp\/v2\/pages\/2\/revisions\/17"}],"wp:attachment":[{"href":"https:\/\/fs.wp.odu.edu\/pkraj\/wp-json\/wp\/v2\/media?parent=2"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}