Notch activates gene transcription in the nucleus of cells, and depending on the biochemical context, it turns certain pathways on, and others off. "To the extent that we know where, and in which cells Notch is acting, we may be able to figure out how Notch works in the thymus," says co-lead author Arivazhagan Sambandam, PhD, Research Associate, also in the Department of Pathology and Laboratory Medicine.
"Studying events in the thymus is important because intrathymic events may be a bottleneck in T-cell reconstitution, which is deficient in post-transplant patients," says co-lead author Ivan Maillard, MD, PhD, Research Associate in the Division of Hematology-Oncology and the Abramson Family Cancer Research Institute. "What the study allows us to do is begin to define exactly where intrathymic Notch signaling happens and where to look for problems and for the relevant molecular interactions."
In many clinical situations, early T-cell progenitors are likely to be deficientespecially in patients undergoing bone marrow or hematopoietic stem cell transplantation, in whom new T cells fail to be produced for long periods of time. In some, especially elderly patients, there is never true recovery of T cells, and such non-recovery is associated with problems such as infections. To improve the outcome of transplant patients, the process of T-cell development needs to be better understood. This may also be important in cancer patients who get profound immunosuppression from treatments and in AIDS patients when T cells are not made at a sufficient rate to replenish the T-cell pool.
The Pear and Bhandoola labs plan to apply the knowledge gained in their basic scientific studies to the clinic. According to Maillard, "In humans, it's more difficult to look inside the thymus, but we plan to use our unique Notch reagents in model system
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
6-Jul-2005