Modeling BK Virus Infection in Renal Transplant Recipients.
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2024-12
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Abstract
Kidney transplant recipients require a lifelong protocol of immunosuppressive therapy to prevent graft rejection. However, these same medications leave them susceptible to opportunistic infections. One pathogen of particular concern is human polyomavirus 1, also known as BK virus (BKPyV). This virus attacks kidney tubule epithelial cells and is a direct threat to the health of the graft. Current standard of care in BK virus-infected transplant recipients is reduction in immunosuppressant therapy, to allow the patient's immune system to control the virus. This requires a delicate balance; immune suppression must be strong enough to prevent rejection, yet weak enough to allow viral clearance. We seek to model viral and immune dynamics with the ultimate goal of applying optimal control methods to this problem. In this paper, we begin with a previously published model and make simplifying assumptions that reduce the number of parameters from 20 to 14. We calibrate our model using newly available patient data and a detailed sensitivity analysis. Numerical results for multiple patients are given to show that the newer model reflects observed dynamics well.
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Myers, Nicholas, Dana Droz, Bruce W Rogers, Hien Tran, Kevin B Flores, Cliburn Chan, Stuart J Knechtle, Annette M Jackson, et al. (2024). Modeling BK Virus Infection in Renal Transplant Recipients. Viruses, 17(1). p. 50. 10.3390/v17010050 Retrieved from https://hdl.handle.net/10161/32119.
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Scholars@Duke
Chi Wei Cliburn Chan
Computational immunology (stochastic and spatial models and simulations, T cell signaling, immune regulation)
Statistical methodology for immunological laboratory techniques (flow cytometry, CFSE analysis, receptor-ligand binding and signaling kinetics)
Informatics of the immune system (reference and application ontologies, meta-programming, text mining and machine learning)
Stuart Johnston Knechtle
During my career as an academic surgeon, I have had the privilege of leading and/or participating in a diverse portfolio of hypothesis-driven research projects. These projects have centered on the immunology of surgery and transplantation, including both cellular and antibody-mediated immune responses. During my training I studied the response of hyper-sensitized recipients to allogeneic liver transplantation, and am currently studying means of reducing immunologic memory that might allow more successful transplantation in sensitized recipients. This immune response involves pathways of coagulation, antibody-mediated rejection, and cellular rejection and current work in my lab involves these three pathways. The other major focuses of my work have been co-stimulation blockade and immune cell depletion as approaches to immunologic unresponsiveness or tolerance. My research group has been involved in translational and clinical research to develop these mechanistic tools for the benefit of human organ transplant recipients.
Recent Publications
Knechtle SJ, Shaw JM, Hering BJ, Kraemer K, Madsen JC. Translational impact of NIH-funded nonhuman primate research in transplantation. Sci Transl Med. 2019 Jul 10;11(500). pii: eaau0143. Reprint | Full Text
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