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Pillai Lab

Innate Immune Regulation, Transplantation Tolerance, and Immunotherapy

Research

Research is to see what everybody else has seen, and to think what nobody else has thought.
 Albert Szent-Gyorgyi 

 

The Pillai laboratory studies regulatory cell populations in mice and man and their role in transplantation tolerance. We use murine models of successful transplant tolerance induction regimens to study immune mechanisms and the effects of commonly used clinical transplantation agents on the immune regulatory process in both transplant recipient and donor. We study novel pathways of regulatory induction of immune allo-transplant tolerance through conduct of transplants into wild-type and regulatory T cell deficient host strains, across major histocompatibility barriers. We apply the immune tolerance induction strategies to both wild-type and mutant mice with β-thalassemia major and intermedia as pre-clinical proof of principle for their potential application in pediatric non-malignant blood disorders.

Blood Cells

We also expand and study key human immune regulatory cell populations including Foxp3+ Treg and invariant natural killer T (iNKT) cells and regulatory antigen presenting cells (APC) for application in immunotherapy, both in pediatric allo-transplantation and in the non-transplant setting, as an adjunct to chemo-/radio-therapy. We are developing immunologically sound protocols for ex vivo expansion of key immune regulatory populations from human cellular therapy products, including peripheral blood (PB), bone marrow (BM), and umbilical cord blood (UCB). We are particularly interested in signal transduction in innatte and adaptive regulatory T cells and the pathways governing regulatory cytokine secretion and cytotoxicity in these cells.

Aims

A major goal of current murine pre-clinical work is to optimize non-myeloablative transplantation protocols for children with non-malignant disorders including bone marrow failure syndromes and hemoglobinopathies, and to institute clinical trials of these therapies for children and adults globally. 

4 M Sykes Nat Med Figure

The goals of each cellular product expansion protocol we have developed vary and range from induction of bidirectional (donor-host) tolerance by Treg/iNKT/APC in transplants for non-malignant disorders to augmentation of iNKT cell cytolytic effector function in transplants for pediatric malignancies, or as part of pre-transplant consolidation therapy.

The approaches used within the lab are designed to allow us to maintain a (largely) seamless transition from clinical application to laboratory basic research and back to clinic, with the goal of maximizing potential for meaningful translational application.