Burdine Laboratory Research Focus
The primary goal of the Burdine laboratory, which is a component of the UAMS Division of Surgical Research, is to fully define the immunological functions of the kinase DNA-PKcs. This kinase has long been known for its role in DNA damage repair but more recent studies have indicated a critical role for it in regulation of the immune system including the activation and function of both B and T cells. This new role has raised questions regarding its potential as therapy for immune-related disorders and its impact on cancer progression. Specifically, for us, we are interested in the ability of DNA-PKcs inhibitors to serve as immunosuppression therapy to prevent both acute and chronic solid-organ transplant rejection.
In our recently published paper, we determined that treatment with DNA-PKcs inhibitors prevented the rejection and extended survival of skin graft transplants in a mouse model. This was caused by inhibition of T cell infiltration into the grafts and the production of donor-specific antibodies. Going forward, we are investigating the molecular mechanisms used by DNA-PKcs to control lymphocyte function which include epigenetic mechanisms and control over T cell receptor signaling. We are also working to determine if DNA-PKcs inhibitors can prevent the rejection of allogeneic kidneys in pig kidney transplant studies.
Given its effects on T cells, we are also investigating how DNA-PKcs impacts cancer immunotherapy and the migration and cytotoxicity of T cells in melanoma mouse models. Additionally, we have preliminary data indicating that DNA-PKcs drives metastasis of primary tumor cells and are investigating this in pancreatic tumor models.
- Schluterman Burdine M, Kim Wiese A, , Turnage RH, Tackett AJ, Burdine LJ. DNA-PKcs controls calcineurin mediated IL-2 production in T lymphocytes. PLoS One. 2017 Jul 27;12(7):e0181608.
- Harrison D, Waldrip Z, Burdine L, Shalin S, Schluterman Burdine M. DNA-PKcs Inhibition Extends Allogeneic Skin Graft Survival. Transplantation, 2020, In Press.