John Driver, Ph.D.
My laboratory is focused on strengthening the immune system of young animals. Enhancing immunity to pathogens has wide ranging benefits for both humans and domestic animals during early life when the immune system is underdeveloped and often incapable of efficiently controlling infection. The vulnerability of young animals to microbes and their ability to respond to vaccinations depends largely on how quickly the developing immune system colonizes lymphoid organs. This can vary significantly between individuals due to a multitude of genetic and environmental effects. Our laboratory seeks to understand these factors in order to develop strategies to improve the resistance of young animals to infection and to promote the development of a robust immune system that will endure in adults. We focus on a particular type of leukocyte called natural killer T (NKT) cells that profoundly affects how cells of the immune system identify and destroy pathogens. The development of NKT cells is strongly influenced by specific nutrients the young animal is exposed to during gestation and lactation. One of our principle objectives is to establish how early nutrition affects the maturation of these cells. This work may help to identify mechanisms that predispose some individuals to infectious agents, and hence reveal dietary and pharmaceutical interventions that prevent disease.
My laboratory also investigates genetic control mechanisms that underlie the development of the autoimmune disease type-1 diabetes (T1D), otherwise unknown as juvenile onset or insulin dependant diabetes. T1D results because genes that normally elicit immune responses to foreign organisms sometimes provide inappropriate signals that direct immune cells to destroy the body’s own insulin-producing pancreatic beta cells. Some of these genes have been identified; however, many remain unaccounted for. An important resource used to identify genes involved in T1D is the NOD (non-obese diabetic) inbred mouse strain that develops the disease in much the same way humans do. However, this strain harbors only a subset of genes that can potentially contribute to T1D. Our laboratory is focused on identifying additional disease-susceptibility genes carried by other inbred mouse strains. Many additional susceptibility genes exist in T1D-resistant mouse strains but the large number of disease-protective genes these stocks possess masks their effects. We have developed techniques to show that a disease resistant strain C57BL/6J harbors a T1D-susceptibility gene(s) with potent effects on how a specific type of immune cell called CD8 T cells destroy beta cells. Identifying the gene(s) responsible for this effect may present new targets for therapeutic interventions and aid in predicting which humans will develop T1D. We are also investigating how vitamin D contributes to the development of T1D in NOD mice. Vitamin D insufficiency has been identified as a potential environmental factor that increases the risk of disease. Our work has shown that vitamin D compounds help to prevent T1D by maintaining the correct balance of calcium in circulation, which promotes healthy beta cell function. These findings may help to identify how disease outcomes may be improved in some T1D-prone individuals that are calcium deficient.
Rivas EI, Driver JP, Garabatos MN, Presa M, Mora C, Rodriguez F, Serreze DV, Stratmann T. 2011. Targeting of a T Cell Agonist Peptide to Lysosomes by DNA Vaccination Induces Tolerance in the Non-Obese Diabetic Mouse. J. Immunol. 186:4078-87.
Driver JP, Chen Y-G, Zhang W, Serreze DV. 2011. Unmasking genes in a type 1 diabetes resistant mouse strain that enhance the peripheral activation of pathogenic CD8 T-cells. Diabetes. 60:1354-9.
Chen Y-G, Scheuplein F, Driver JP, Hewes A, Reifsnyder P, Leiter EH, Serreze DV. 2011, Testing the role of P2X7 receptors in the development of type 1 diabetes in NOD mice. J. Immunol. 186:4278-84.
Serreze DV, Chapman HD, Niens M, Dunn R, Kehry MR, Driver JP, Haller M, Wasserfall C, Atkinson MA. 2011. Loss of Intra-Islet CD20 Expression May Complicate Efficacy of B-Cell-Directed Type 1 Diabetes Therapies. Diabetes. 2011; 60:2914-21.
Driver JP, Lamont DJ, Gysemans C, Mathieu C, Serreze DV. 2011. Calcium Insufficiency Accelerates Type 1 Diabetes in Vitamin D Receptor-Deficient Nonobese Diabetic (NOD) Mice. Endocrinology. 2011; 152:4620-9.