Home | News | Directories | Calendar | Maps | Contact Us | Webmail
Perelman School of Medicine at the University of Pennsylvania Advanced Search

Stephan A. Grupp, MD, PhD

Stephan A. Grupp, MD, PhD

faculty photo
Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
Oncology/BMT CTRB 3006
3501 Civic Center Blvd.
Philadelphia, PA 19104
Office: 215-590-5476
Fax: (215) 590-3770
Education:
B.S.
University of Cincinnati (Magna cum laude), 1981.
Ph.D.
University of Cincinnati College of Medicine, 1985.
M.D.
University of Cincinnati College of Medicine, 1987.
Permanent link
 
Perelman School of Medicine > Faculty > Search

Description of Research Expertise

Research Interests

Role of the B cell receptor complex in B cell signaling and lymphoid development

Research Summary

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 <15% long-term survival with chemo and ~35% with single autologous stem cell transplant (SCT). This has also lead to a phase III trial (ANBL0532) in the COG.

More recently, our group has been working with Dr. Carl June and the Penn Translational Research Program on chimeric antigen receptor (CAR)-based engineered T cell therapies. One target is CD19 in ALL, where we have developed chimeric immunoreceptor-armed T cells in an ongoing basic and translational collaboration with the June group. This approach has now been taken into pilot trials at CHOP and Penn. The first three adult patients on this clinical trial experienced remarkable clinical responses and unprecedented persistence and expansion of the therapeutic cells. We are now seeing similar results in pediatric patients with ALL.

Selected Publications

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 24(8): 717-27, Aug 2013.

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 48(8): 1056-64, Aug 2013.

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 Jul 2013.

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 48(7): 947-52, Jul 2013.

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 Jul 2013.

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 121(26): 5154-7, Jun 2013.

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 60(6): 1044-7, Jun 2013.

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 368(16): 1509-18, Apr 2013.

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 19(4): 569-75, Apr 2013.

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 Dec 2012.

back to top
Last updated: 09/20/2013
The Trustees of the University of Pennsylvania