Engineered T cell therapy
Signal transduction in lymphoid malignancies
Role of the B cell receptor complex in B cell signaling and lymphoid development
Basic Science. The primary focus of my lab?s work is the development of targeted cell therapies and study of molecular signaling pathways in ALL. Our group has leveraged studies using primary human ALL xenografts into treatments being tested in a number of clinical trials.
We have demonstrated the importance of the mTOR pathway in leukemia and lymphoma, and demonstrated that inhibitors of mTOR signal transduction (such as sirolimus) are effective agents against pre-B ALL and against the lymphoproliferative disorder ALPS. These findings have direct translational significance in both ALL and ALPS, leading to Phase I, II, III (ASCT0431) and pilot trials in these diseases. We also demonstrated that signaling through the IL-7 receptor is key in the response of early B ALL cells to mTOR inhibitors. IL-7 and a related molecule called TSLP reverse the effect of mTOR inhibitors on pre-B ALL cells, providing insights into the potential mechanisms of the mTOR effect and a further opportunity for signal transduction inhibition in ALL. We are the ALL Xenograft Core Lab for the COG.
Translational. As the CCCR Director of Translational Research, I oversee research into clinical use of hematopoietic stem cells and T cell-based therapies. As an example, we have performed trials to improve outcome in neuroblastoma (NBL), a disease that has
- Assistant Professor of Pediatrics at University of Pennsylvania School of Medicine (1996 – 2006)
- Professor of Pediatrics at University of Pennsylvania School of Medicine (2012– present)
- Associate Professor of Pediatrics at University of Pennsylvania School of Medicine (2006 – 2012)
- M.D., University of Cincinnati College of Medicine (1987)
- Ph.D., University of Cincinnati College of Medicine (1985)
- B.S., University of Cincinnati (Magna cum laude) (1981)