Eric Wieder, Ph.D.
Associate Professor of Medicine
Description of Research
Dr. Wieder’s current focus in cancer research is in immunology in the context of stem cell transplantation. His expertise is in complex multi-color flow cytometry and in assays of immune function. A major focus of his research is to develop strategies to reduce graft-versus-host disease in allogeneic stem cell transplant recipients. Graft-versus-leukemia effects need to be improved while reducing graft-versus-host disease. This can be accomplished through graft engineering. Dr. Wieder's laboratory has actively pursued in preclinical efforts the ex-vivo expansion of regulatory T cells (Tregs) for add-back to the stem cell graft to suppress graft-verus-host disease.
In addition, a major problem for cancer patients who could potentially benefit from stem cell transplant is the lack of a suitable donor. Cord blood (CB) has been used as a source of stem cells for transplant, but Dr. Wieder found that immune recovery is very slow in patients transplanted with CB stem cells. Using a 9-color flow cytometry approach to determining T cell differentiation, he also found reconstituted T cells in CB patients were highly enriched for late memory T cells (which are not good at proliferating) compared to other transplant patients. Therefore, Dr. Wieder is interested in pursuing strategies to improve both thymic output and T cell function in those patients. Since administration of immunosuppressive agents post-transplant can reduce immune recovery, he is also pursuing the use of expanded Tregs in cord blood patients as an alternative to immunosuppressive agents. Dr. Wieder has begun to explore the role of lymphoid or T progenitor cell dose during transplantation on T and overall immune reconstitution post-transplant.
Finally, because cells responsible for creating graft-versus-host disease (alloreactive) are mostly found in the naive or early memory T cell compartment, whereas virus-specific T cells in the host are mostly in late memory cells, Dr. Wieder is seeking targets to allow for selective suppression of naive and early T cells while sparing late memory T cells. With the appropriate target(s) it should be possible to reduce the initiation of graft-versus-host disease while preventing viral infection/activation in transplant patients.
- Has demostrated thousand-fold expansion of Tregs without loss of phenotype or function in pre-clinical experiments
- Showed that Vitamin D receptor is upregulated very early during alloreactive T cell activation and tracks closely with T cell function
- Found that late memory T cells have a distinct cytokine production profile with loss of IL-2 production and CC chemokine production