Stephan A. Grupp, MD, PhD

faculty photo
Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
The Children's Hospital of Philadelphia
Colket Translational Research Building, Room 3006
3501 Civic Center Boulevard
Philadelphia, PA 19104
Office: 215-590-5475
Fax: (215) 590-3770
University of Cincinnati (Magna cum laude), 1981.
University of Cincinnati College of Medicine, 1985.
University of Cincinnati College of Medicine, 1987.
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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

Haydar Frangoul, M.D., David Altshuler, M.D., Ph.D., M. Domenica Cappellini, M.D., Yi-Shan Chen, Ph.D., Jennifer Domm, M.D., Brenda K. Eustace, Ph.D., Juergen Foell, M.D., Josu de la Fuente, M.D., Ph.D., Stephan Grupp, M.D., Ph.D., Rupert Handgretinger, M.D., Tony W. Ho, M.D., Antonis Kattamis, M.D., Andrew Kernytsky, Ph.D., Julie Lekstrom-Himes, M.D., Amanda M. Li, M.D., Franco Locatelli, M.D., Markus Y. Mapara, M.D., Ph.D., Mariane de Montalembert, M.D., Damiano Rondelli, M.D., Akshay Sharma, M.B., B.S., Sujit Sheth, M.D., Sandeep Soni, M.D., Martin H. Steinberg, M.D., Donna Wall, M.D., Angela Yen, Ph.D., and Selim Corbacioglu, M.D.: CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. The New England Journal of Medicine Dec 2020 Notes: Epub ahead of print.

Marcelo C. Pasquini, Zhen-Huan Hu, Kevin Curran, Theodore Laetsch, Frederick Locke, Rayne Rouce, Michael A. Pulsipher, Christine L. Phillips, Amy Keating, Matthew J. Frigault, Dana Salzberg, Samantha Jaglowski, Joshua P. Sasine, Joseph Rosenthal, Monalisa Ghosh, Daniel Landsburg, Steven Margossian, Paul L. Martin, Manali K. Kamdar, Peiman Hematti, Sarah Nikiforow, Cameron Turtle, Miguel-Angel Perales, Patricia Steinert, Mary M. Horowitz, Amy Moskop, Lida Pacaud, Lan Yi, Raghav Chawla, Eric Bleickardt, Stephan Grupp: Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Advances 4(21): 5414–5424, Nov 2020.

Caroline Diorio, Sarah E Henrickson, Laura A Vella, Kevin O McNerney, Julie Chase, Chakkapong Burudpakdee, Jessica H Lee 1, Cristina Jasen 1 3, Fran Balamuth 6, David M Barrett 1 2, Brenda L Banwell, Kathrin M Bernt, Allison M Blatz, Kathleen Chiotos, Brian T Fisher, Julie C Fitzgerald, Jeffrey S Gerber, Kandace Gollomp, Christopher Gray, Stephan A Grupp, Rebecca M Harris, Todd J Kilbaugh, Audrey R Odom John, Michele Lambert, Emily J Liebling, Michele E Paessler, Whitney Petrosa, Charles Phillips, Anne F Reilly, Neil D Romberg, Alix Seif, Deborah A Sesok-Pizzini, Kathleen E Sullivan, Julie Vardaro, Edward M Behrens, David T Teachey, Hamid Bassiri: Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. Journal of Clinical Investigation (JCI) 130(11): 5967-5975, Nov 2020.

Caroline Diorio, Pamela A. Shaw, Edward Pequignot, Alena Orlenko, Fang Chen, Richard Aplenc, David M. Barrett, Hamid Bassiri, Edward Behrens, Amanda M. DiNofia, Vanessa Gonzalez, Natalka Koterba, Bruce L. Levine, Shannon L. Maude, Nuala J. Meyer, Jason H. Moore, Michele Paessler, David L. Porter, Jenny L. Bush, Don L. Siegel, Megan M. Davis, Donglan Zhang, Carl H. June, Stephan A. Grupp, J. Joseph Melenhorst, Simon F. Lacey, Scott L. Weiss, David T. Teachey: Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children. Blood Advances 4(20): 5174–5183, Oct 2020.

Rajat K Das, Roddy S O'Connor, Stephan A Grupp, David M Barrett: Lingering effects of chemotherapy on mature T cells impair proliferation. Blood Adv. 4(19): 4653-4664, Oct 2020.

Paul G Richardson, Angela R Smith, Nancy A Kernan, Leslie Lehmann, Robert J Ryan, Stephan A Grupp: Analysis of Time to Complete Response after Defibrotide Initiation in Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant S1083-8791(20): 30596-6, Sept 2020.

Asnani M, Hayer KE, Naqvi AS, Zheng S, Yang SY, Oldridge D, Ibrahim F, Maragkakis M, Gazzara MR, Black KL, Bagashev A, Taylor D, Mourelatos Z, Grupp SA, Barrett D, Maris JM, Sotillo E, Barash Y, Thomas-Tikhonenko A.: Retention of CD19 intron 2 contributes to CART-19 resistance in leukemias with subclonal frameshift mutations in CD19. Leukemia 34(4): 1202-1207, Apr 2020.

Singh N, Lee YG, Shestova O, Ravikumar P, Hayer KE, Hong SJ, Lu XM, Pajarillo R, Agarwal S, Kuramitsu S, Orlando EJ, Mueller KT, Good CR, Berger SL, Shalem O, Weitzman MD, Frey NV, Maude SL, Grupp SA, June CH, Gill S, Ruella M.: Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction. Cancer Discovery 10(4): 552-567, Apr 2020.

Arnold DE, Maude SL, Callahan CA, DiNofia AM, Grupp SA, Heimall JR.: Subcutaneous immunoglobulin replacement following CD19-specific chimeric antigen receptor T-cell therapy for B-cell acute lymphoblastic leukemia in pediatric patients. Pediatr Blood Cancer. 67(3): e28092, Mar 2020.

Tal Schechter-Finkelstein, Evelio Perez-Albuerne, Lin TF, Meredith S. Irwin, Essa M, Desai AV, Frangoul H, Gregory A. Yanik, L. Lee Dupuis, David A. Jacobsohn, Morris Kletzel, Ranalli M, Soni S, Seif AE, Stephan A. Grupp, Christopher C. Dvorak: Veno-occlusive disease after high-dose busulfan-melphalan in neuroblastoma. Bone Marrow Transplantation 55(3): 531-537, Mar 2020.

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Last updated: 01/07/2021
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