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My lab has had a long-standing interest in understanding the basis of immunological tolerance and humoral immunity following allogeneic transplantation. We have been collaborating extensively with Dr. Marisa Alegre in studying how infections prevent the induction of transplantation tolerance or destabilize established tolerance, and understanding the fundamental mechanisms of robust transplantation tolerance. We recently have developed new approaches to track a defined population of endogenous allospecific T (CD4+effectors (Th1 and Tfh), CD4+Tregs and CD8 effector) and B cells (Class I and Class II reactive), and are now asking how each of these subsets of cells behave under conditions of rejection, memory/sensitization and tolerance, with the goal of identifying new biomarkers of tolerance and rejection.
We also actively investigating the behavior of memory alloreactive B cells in the setting of transplantation, and in identifying how these cells differ from naïve B cells, with the goal of identifying immunosuppressive and tolerance inducing strategies to control this clinically important subset of cells. We are conducting these studies in experimental rodent models, and also testing our findings in humans. These studies are performed in collaboration with Dr. Roger Sciammas at UCDavis, and the clinical transplant faculty at the University of Chicago and Ohio State University.
In addition, we have stretched our research into the prevention of infections through vaccination, with the long-term goal of using this strategy as an indirect but cost-effective means of stabilizing tolerance. Towards this goal, my lab has been collaborating with Dr. Chris Montgomery, a physician scientist in the Department of Pediatrics, to identify sub-unit vaccine candidates and to investigate the immunobiology of protection from Staphylococcus aureus skin infections. My lab also has a strong program of collaborative research with Dr. Joel Collier, a bioengineer at Duke University, to develop of nanoparticulate adjuvant-free vaccines that can elicit protective immune responses with minimal inflammation. Such a vaccine that elicits minimal inflammation may be ideal for tolerant patients, as we now appreciate that inflammation can destabilize established tolerance.
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