PhD Grad: MacKenzie D. Williams
Mentor: Dr. Mark Atkinson
Dr. MacKenzie Williams’ role within the University of Florida Diabetes Institute followed a unique evolution: first as a “friend of the lab” while working as a barista at Opus Coffee, then a brief time as a research technician in Dr. Mark Atkinson’s laboratory, and finally as a student in the Biomedical Sciences graduate program at UF in the Atkinson lab. MacKenzie should be commended, not only for her important contributions to the field of biomedical research and more specifically type 1 diabetes, but beyond that, for her unparalleled work ethic. She initially tackled the notion of how genes forming susceptibility to type 1 diabetes might contribute to the disease through their function. Specifically, she sought to determine whether a genetic variant associated with two proteins known as Toll-like receptor 7 and Toll-like receptor 8, which are responsible for viral sensing by the immune system, would modulate immune cell signaling and function, thereby contributing to the development of the autoimmune disease, type 1 diabetes. Dr. Williams put forth an exceptional effort involving a number of well-planned and well-executed experiments. Though the data did not support the hypothesis that TLR7/8 gene-specific effects might drive aberrant immune responses or type 1 diabetes, her findings have expanded our knowledge of genetic regulation of viral sensing pathways and downstream immune cell functions. From there, MacKenzie explored the hypothesis that islet autoantibody titers might serve as biomarkers to predict and monitor the rate of decline of residual insulin production in patients with type 1 diabetes, with a multifactorial genetic risk score potentially modulating this dynamic relationship. She assayed hundreds of serum samples for three islet autoantibodies, as well as the insulin production marker C-peptide, and developed an impressive knowledge of both the genetics of type 1 diabetes and statistical modeling methods. The resulting data support a model wherein the probability of detecting insulin production in patients with type 1 diabetes is best predicted by titers of all three autoantibodies, as well as the genetic risk score over the course of disease duration. We see this information as a critical step toward precision medicine for type 1 diabetes patients, with applications for this model seeing relevance in guiding subject enrollment and outcomes-monitoring for clinical trials, and potentially guiding treatment decisions in the clinical setting thereafter. We are delighted that Dr. Williams will be staying on as a post-doctoral associate in Dr. Clive Wasserfall’s lab within the UF Diabetes Institute.