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Pillai Lab: About Us

Pillai Lab (from left): Taren Ong, Marie van der Merwe, Ursula Leflore (admin), Asha Pillai,
Wioleta Luszczek, Vanessa Morales-Krafcik.

About Us

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.

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 innate 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 at St. Jude.

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.

Peripheral blood smear of murine HW-80 (H-2^b) β-thalassemic mouse before (left) and 28 days after (right) immunomodulatory pre-transplant conditioning and transplantation of bone marrow and high-doses of peripheral CD3+ T cells from major histocompatibility complex (MHC)-mismatched BALB/c (H-2^d) donors. Transplanted mice develop stable mixed donor-host hematopoietic chimerism and are free from lethal GVHD. Photographs courtesy Peter Vogel, DVM

Funding

Support for the murine transplant tolerance projects is provided by:

• National Heart Lung and Blood Institute (NIH K08)

• ALSAC/St. Jude - the fundraising organization of St. Jude Children's Research Hospital

• Sumara Endowed Fellowship in Cellular and Gene Therapy (to Marie van der Merwe)

Support for human regulatory T cell expansions is provided by:

• ALSAC/St. Jude - the fundraising organization of St. Jude Children's Research Hospital

• National Cancer Institute/St Jude (Cancer Center Support Grant)

• Hyundai Foundation (Hyundai Scholars Program)

• The Assissi Foundation

• Dunbar Foundation