Signal transduction pathways and signal transduction inhibitors in ALL, cellular therapeutics.
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)
- Barrett David M, Liu Xiaojun, Jiang Shuguang, June Carl H, Grupp Stephan A, Zhao Yangbing. Regimen-Specific Effects of RNA-Modified Chimeric Antigen Receptor T Cells in Mice with Advanced Leukemia. Human gene therapy. Vol 24(8) . 2013 Aug:717-27.
- Hale G A, Arora M, Ahn K W, He W, Camitta B, Bishop M R, Bitan M, Cairo M S, Chan K, Childs R W, Copelan E, Davies S M, Perez M A D, Doyle J J, Gale R P, Vicent M G, Horn B N, Hussein A A, Jodele S, Kamani N R, Kasow K A, Kletzel M, Lazarus H M, Lewis V A, Myers K C, Olsson R, Pulsipher M, Qayed M, Sanders J E, Shaw P J, Soni S, Stiff P J, Stadtmauer E A, Ueno N T, Wall D A, Grupp S A. Allogeneic hematopoietic cell transplantation for neuroblastoma: the CIBMTR experience. Bone Marrow Transplantation. Vol 48(8) . 2013 Aug:1056-64.
- Kreissman Susan G, Seeger Robert C, Matthay Katherine K, London Wendy B, Sposto Richard, Grupp Stephan A, Haas-Kogan Daphne A, Laquaglia Michael P, Yu Alice L, Diller Lisa, Buxton Allen, Park Julie R, Cohn Susan L, Maris John M, Reynolds C Patrick, Villablanca Judith G. Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial. The Lancet Oncology. 2013 Jul.
- Seif A E, Naranjo A, Baker D L, Bunin N J, Kletzel M, Kretschmar C S, Maris J M, McGrady P W, von Allmen D, Cohn S L, London W B, Park J R, Diller L R, Grupp S A. A pilot study of tandem high-dose chemotherapy with stem cell rescue as consolidation for high-risk neuroblastoma: Children's Oncology Group study ANBL00P1. Bone marrow transplantation. Vol 48(7) . 2013 Jul:947-52.
- Schultz Kirk R, Baker K Scott, Boelens Jaap J, Bollard Catherine M, Egeler R Maarten, Cowan Mort, Ladenstein Ruth, Lankester Arjan, Locatelli Franco, Lawitschka Anita, Levine John E, Loh Mignon, Nemecek Eneida, Niemeyer Charlotte, Prasad Vinod K, Rocha Vanderson, Shenoy Shalini, Strahm Brigitte, Veys Paul, Wall Donna, Bader Peter, Grupp Stephan A, Pulsipher Michael A, Peters Christina. Challenges and Opportunities for International Cooperative Studies in Pediatric Hematopoeitic Cell Transplantation: Priorities of the Westhafen Intercontinental Group. Biology of blood and marrow transplantation. 2013 Jul.
- Teachey David T, Rheingold Susan R, Maude Shannon L, Zugmaier Gerhard, Barrett David M, Seif Alix E, Nichols Kim E, Suppa Erica K, Kalos Michael, Berg Robert A, Fitzgerald Julie C, Aplenc Richard, Gore Lia, Grupp Stephan A. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. Vol 121(26) . 2013 Jun:5154-7.
- Grupp Stephan A, Dvorak Christopher C, Nieder Michael L, Levine John E, Wall Donna A, Langholz Bryan, Pulsipher Michael A. Children's Oncology Group's 2013 blueprint for research: stem cell transplantation. Pediatric Blood & Cancer. Vol 60(6) . 2013 Jun:1044-7.
- Grupp Stephan A, Kalos Michael, Barrett David, Aplenc Richard, Porter David L, Rheingold Susan R, Teachey David T, Chew Anne, Hauck Bernd, Wright J Fraser, Milone Michael C, Levine Bruce L, June Carl H. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. The New England Journal of Medicine. Vol 368(16) . 2013 Apr:1509-18.
- Goyal Rakesh K, Han Kelong, Wall Donna A, Pulsipher Michael A, Bunin Nancy, Grupp Stephan A, Mada Sripal R, Venkataramanan Raman. Sirolimus pharmacokinetics in early postmyeloablative pediatric blood and marrow transplantation. Biology of Blood and Marrow Transplantation. Vol 19(4) . 2013 Apr:569-75.
- Goyal, RK, K Han, DA Wall, MA Pulsipher, N Bunin, SA Grupp, SR Mada, and R Venkataramanan.. Sirolimus pharmacokinetics in early post myeloablative pediatric blood and marrow transplantation.. Biology of Blood and Marrow Transplantation. 2012 Dec.