David C. Fajgenbaum, MD, MBA, MSc

faculty photo
Associate Professor of Medicine (Translational Medicine and Human Genetics)
Associate Director, Patient Impact, Orphan Disease Center, University of Pennsylvania
Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania
Member, Orphan Disease Center, University of Pennsylvania
Senior Fellow, Leonard Davis Institute for Health Economics, University of Pennsylvania
Member, Institute for Immunology, University of Pennsylvania
Founding Director, Center for Cytokine Storm Treatment & Laboratory (CSTL), University of Pennsylvania
Member, Medical Scientist Training Program Admissions Committee, University of Pennsylvania
Chair, Strategic Planning Research Committee, Division of Translational Medicine & Human Genetics, University of Pennsylvania
Leadership Council Member, Colton Center for Autoimmunity, University of Pennsylvania
Department: Medicine
Graduate Group Affiliations

Contact information
David C. Fajgenbaum
University of Pennsylvania, Perelman School of Medicine
Division of Translational Medicine & Human Genetics
Center for Cytokine Storm Treatment & Laboratory (CSTL)
3535 Market Street
Suite 700, Room 717
Philadelphia, PA 19104
Fax: 877-991-9674
Lab: 215-614-0935
BS (Honors Human Sciences with Distinction, Magna Cum Laude)
Georgetown University, Washington, DC, 2007.
MSc (Public Health)
University of Oxford, Oxford, UK, 2008.
MD (Medicine)
University of Pennsylvania Perelman School of Medicine, 2013.
MBA (Health Care Management Program)
Wharton School of Business, University of Pennsylvania, 2015.
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Description of Other Expertise

David Fajgenbaum, MD, MBA, MSc, FCPP, is an Associate Professor of Medicine in Translational Medicine & Human Genetics at the University of Pennsylvania, Founding Director of the Center for Cytokine Storm Treatment & Laboratory (CSTL), Associate Director, Patient Impact of the Penn Orphan Disease Center, and Co-Founder/President of the Castleman Disease Collaborative Network (CDCN). He is also the national bestselling author of 'Chasing My Cure: A Doctor's Race to Turn Hope Into Action' (http://www.ChasingMyCure.com) and a patient battling idiopathic multicentric Castleman disease (iMCD). He is in his longest remission ever thanks to a precision treatment that he identified, which had never been used before for iMCD. He has also identified and/or advanced 15 other treatment approaches for iMCD and cancer. He recently co-founded Every Cure, a nonprofit organization on a mission to unlock the full potential of FDA-approved drugs to treat every disease they possibly can.

One of the youngest tenured professors in the history of Penn Medicine and one of the youngest awardees of multiple top NIH and FDA grants, Fajgenbaum has published scientific papers in high-impact journals such as the New England Journal of Medicine, Journal of Clinical Investigation, and Lancet, been recognized with awards such as the 2016 Atlas Award along with then Vice President Joe Biden and the 2021 NDRI Service to Science Award along with Nobel Laureates Katalin Kariko and Drew Weissman, and profiled in a cover story by The New York Times as well as by Good Morning America, CNN, Forbes 30 Under 30, and the Today Show. Fajgenbaum serves on the Board of Directors for the Reagan-Udall Foundation for the FDA, co-Chair of the Advisory Board for the CURE Drug Repurposing Collaboratory, and co-Chair of the Scientific Advisory Board for the CDCN.

Dr. Fajgenbaum earned a BS in Human Sciences with Distinction from Georgetown University, where he was USA Today Academic All-USA First Team and a Quarterback on the Division I football team, a MSc in Public Health from the University of Oxford as the 2007 Joseph L. Allbritton Scholar, a MD from the Perelman School of Medicine at the University of Pennsylvania, where he was a 21st Century Gamble Scholar, and a MBA from The Wharton School, where he was awarded the Joseph Wharton Award, Core Value Leadership Award, Kissick Scholarship, Wharton Business Plan Competition Social Impact Prize, Eilers Health Care Management Award, Mandel Fellowship, and Commencement Speaker.

Description of Research Expertise

See https://www.med.upenn.edu/CSTL/ for more information.

Research interests:
Elucidating the etiology, dysregulated cell types, signaling pathways, and effector cytokines in idiopathic multicentric Castleman disease (iMCD) and related cytokine storm disorders; identifying effective treatments for iMCD patients; PI3K/Akt/mTOR signaling in iMCD; role of stromal cells and chemokines in iMCD; methods for accelerating drug development and drug repurposing

IL-6, cytokine storm, stromal cells; chemokines, PI3K/Akt/mTOR

Research summary:
1) Elucidating the etiology, dysregulated cell types, signaling pathways, and effector cytokines in idiopathic multicentric Castleman disease (iMCD) and related cytokine storm disorders
iMCD is a poorly-understood and deadly hematologic disorder. A proinflammatory cytokine storm and reactive lymphoproliferation occur for an unknown etiology. The poor understanding of etiology and pathogenesis has limited the development of effective treatments and contributed to the significant morbidity and mortality associated with iMCD (55-77% 5-year overall survival). Currently, we leverage a variety of techniques to study the etiology and pathogenesis of iMCD. In addition, we leverage a biobank (CastleBank) to collect samples to fuel our translational research.

2) Identifying effective treatments for iMCD patients
The poor understanding of iMCD pathogenesis has slowed the development of treatment approaches. Currently, there is only one FDA-approved treatment for iMCD, which is effective in approximately one-third or patients. We run an international Natural History Study of Castleman Disease (ACCELERATE) to collect in-depth data on patients around the world to identify effective treatment approaches currently being used off-label.

3) PI3K/Akt/mTOR signaling in iMCD
Proteomic, flow cytometric, and immunostaining studies revealed upregulation of Vascular Endothelial Growth Factor (VEGF), activated CD8+ T cells, and uncontrolled PI3K/Akt/mTOR signaling in iMCD. Whole genome sequencing of an iMCD patient and both parents revealed rare compound heterozygous missense mutations in both alleles of a negative regulator of T cell activation and a candidate etiological mechanism. These novel findings led to the first-ever use of sirolimus in iMCD and a prolonged remission for a refractory patient (manuscript in submission). Drawing upon the world’s largest collection of iMCD patients and their biospecimens in ACCELERATE, we are employing whole genome sequencing, transcriptomics, proteomics, flow cytometry and phospho-flow, and cellular signaling assays to continue to elucidate the role of PI3K/Akt/mTOR signaling in iMCD. As there are no animal models, we are also performing extensive correlative studies to quantify changes in VEGF, T cell activation, PI3K/Akt/mTOR signaling, and other immunological markers following in vivo sirolimus administration to patients and documenting treatment efficacy.

4) Investigating the role of stromal cells and chemokines in iMCD
Quantification of 1,129 plasma proteins in iMCD revealed highly up-regulated acute phase reactants and chemokines. The chemokines that were most upregulated are essential for normal lymph node morphology/function and typically produced by lymph node stromal cells. The most up-regulated chemokine, CXCL13, is responsible for homing B cells into the germinal center. This is interesting, because the pathological hallmark of iMCD is dysmorphic lymph node germinal centers with either too few (atrophic) or too many B cells (hyperplastic). Immunohistochemistry confirmed significantly increased germinal center expression of CXCL13. We are exploring the mechanisms of lymph node stromal cell activation and chemokine signaling.

Rotation Projects are available in all areas

Lab personnel:
Josh Brandstadter, MD, PhD, Director of Clinical Research
Melanie Mumau, PhD, Associate Director of Translational Research
Michael Gonzalez, PhD, Associate Director of Computational Research
Daniel Korn, PhD, Data Scientist
Tracey Sikora, Associate Director of Drug Repurposing
Bridget Austin, Biobank Program Manager
Abiola Irvine, Research Specialist
Ira Miller, Research Specialist
Saishravan Shyamsundar, Data Analyst
Mateo Sarmiento Bustamante, Data Analyst
Criswell Lavery, Research Administration Coordinator
Amber Cohen, Executive Administrator
Brent Shaw, Medical Communications Fellow
Sally Nijim, 2023-2024 Biomedical Leadership Fellow, MS3

The Center for Cytokine Storm Treatment & Laboratory and Fajgenbaum Lab are currently searching for multiple new roles. Visit https://www.cstlupenn.org/joinus for more information.

Selected Publications

Luke Y. C. Chen, Brian F. Skinnider, Don Wilson, David C. Fajgenbaum: Adrenalitis and anasarca in idiopathic multicentric Castleman’s disease. The Lancet. 397(10286): 1749, 2021.

Sheila K. Pierson, Sushila Shenoy, Ana B. Oromendia, Alexander Gorzewski, Ruth-Anne Langan, Christopher Shield Nabel, Jason R Ruth, Sophia A. T. Parente, Daniel J. Arenas, Mary Guilfoyle, Manjula Reddy, Michael Weinblatt, Nancy Shadick, Mark Bower, Alessia Dalla Pria, Yasufumi Masaki, Laura Katz, Jason Mezey, Philip Beineke, David Lee, Craig Tendler, Taku Kambayashi, Alexander Fossa, Frits van Rhee, David C. Fajgenbaum: Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease. Blood Advances. 5(17): 3445-3456, 2021.

David C. Fajgenbaum & Carl H. June: Cytokine Storm. New England Journal of Medicine. 383(23): 2255–2273, 2020.

Daniel J. Arenas, Katherine Floess, Dale Kobrin, Ruth-Anne Langan Pai, Maya B. Srkalovic, Mark-Avery Tamakloe, Rozena Rasheed, Jasira Ziglar, Johnson Khor, Sophia A. T. Parente, Sheila K. Pierson, Daniel Martinez, Gerald B. Wertheim, Taku Kambayashi, Joseph Baur, David T. Teachey, David C. Fajgenbaum: Increased mTOR activation in idiopathic multicentric Castleman disease. Blood. 135(19): 1673–1684, 2020.

Sheila K. Pierson, Johnson S. Khor, Jasira Ziglar, Amy Liu, Katherine Floess, Erin NaPier, Alexander Gorzewski, Mark-Avery Tamakloe, Victoria Powers, Faizaan Akhter, Eric Haljasmaa, Raj Jayanthan, Arthur Rubenstein, Mileva Repasky, Kojo Elenitoba-Johnson, Jason Ruth, Bette Jacobs, Matthew Streetly, Linus Angenendt, Jose Luis Patier, Simone Ferrero, Pier Luigi Zinzani, Louis Terriou, Corey Casper, Elaine Jaffe, Christian Hoffmann, Eric Oksenhendler, Alexander Fossa, Gordan Srkalovic, Amy Chadburn, Thomas S. Uldrick, Megan Lim, Frits van Rhee, David C. Fajgenbaum: ACCELERATE: A Patient-Powered Natural History Study Design Enabling Clinical and Therapeutic Discoveries in a Rare Disorder. Cell Reports Medicine. 1(9): 100158, 2020.

Ruth-Anne Langan Pai, Alberto Sada Japp, Michael Gonzalez, Rozena F. Rasheed, Mariko Okumura, Daniel Arenas, Sheila K. Pierson, Victoria Powers, Awo Akosua Kesewa Layman, Charlly Kao, Hakon Hakonarson, Frits van Rhee, Michael R. Betts, Taku Kambayashi, David C. Fajgenbaum: Type I IFN response associated with mTOR activation in the TAFRO subtype of idiopathic multicentric Castleman disease. JCI Insight. 5(9): e135031, 2020.

Angela Dispenzieri & David C. Fajgenbaum: Overview of Castleman Disease. Blood. 135(16): 1353–1364, 2020.

Frits van Rhee, Eric Oksenhendler, Gordan Srkalovic, Peter Voorhees, Megan Lim, Makoto Ide, Sophia Parente, Stephen Schey, Matthew Streetly, Raymond Wong, David Wu, Ivan Maillard, Joshua Brandstadter, Nikhil Munshi, Angela Dispenzieri, Kojo S. Elenitoba-Johnson, Alexander Fössa, Mary Jo Lechowicz, Shanmuganathan Chandrakasan, Sheila K. Pierson, Amy Greenway, Sunita Nasta, Kazuyuki Yoshizaki, Razelle Kurzrock, Thomas S. Uldrick, Corey Casper, David C. Fajgenbaum: International, evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman Disease. Blood Advances. 4(23): 6039-6050, 2020.

David C. Fajgenbaum: Chasing My Cure: A Doctor's Race to Turn Hope Into Action. Ballantine (an imprint of Penguin Random House). 2019.

David C. Fajgenbaum, Ruth-Anne Langan, Alberto Sada Japp, Helen L. Partridge, Sheila K. Pierson, Amrit Singh, Daniel J. Arenas, Jason R. Ruth, Christopher S. Nabel, Katie Stone, Mariko Okumura, Anthony Schwarer, Fabio Freire Jose, Nelson Hamerschlak, Gerald B. Wertheim, Michael B. Jordan, Adam D. Cohen, Vera Krymskaya, Arthur Rubenstein, Michael R. Betts, Taku Kambayashi, Frits van Rhee, Thomas S. Uldrick: Identifying and targeting pathogenic PI3K/AKT/mTOR signaling in IL-6-blockade-refractory idiopathic multicentric Castleman disease. Journal of Clinical Investigation. 129(10): 4451-4463, 2019.

David C. Fajgenbaum, Thomas S. Uldrick, Adam Bagg, Dale Frank, David Wu, Gordan Srkalovic, David Simpson, Amy Y. Liu, David Menke, Shanmuganathan Chandrakasan, Mary Jo Lechowicz, Raymond S.M. Wong, Sheila Pierson, Michele Paessler, Jean-Francois Rossi, Makoto Ide, Jason Ruth, Michael Croglio, Alexander Suarez, Vera Krymskaya, Amy Chadburn, Gisele Colleoni, Sunita Nasta, Raj Jayanthan, Christopher S. Nabel, Corey Casper, Angela Dispenzieri, Alexander Fossa, Dermot Kelleher, Razelle Kurzrock, Peter Voorhees, Ahmet Dogan, Kazuyuki Yoshizaki, Frits van Rhee, Eric Oksenhendler, Elaine S. Jaffe, Kojo S.J. Elenitoba-Johnson, Megan S. Lim: International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 129(12): 1646-1657, 2017.

Frits van Rhee, Peter Voorhees, Angela Dispenzieri, Alexander Fossa, Gordan Srkalovic, Makoto Ide, Nikhil Munshi, Stephen Schey, Matthew Streetly, Sheila K. Pierson, Helen L. Partridge, Sudipto Mukherjee, Dustin Shilling, Katie Stone, Amy Greenway, Jason Ruth, Mary Jo Lechowicz, Shanmuganathan Chandrakasan, Raj Jayanthan, Elaine S. Jaffe, Heather Leitch, Naveen Pemmaraju, Amy Chadburn, Megan S. Lim, Kojo S. Elenitoba-Johnson, Vera Krymskaya, Aaron Goodman, Christian Hoffmann, Pier Luigi Zinzani, Simone Ferrero, Louis Terriou, Yasuharu Sato, David Simpson, Raymond Wong, Jean-Francois Rossi, Sunita Nasta, Kazuyuki Yoshizaki, Razelle Kurzrock, Thomas S. Uldrick, Corey Casper, Eric Oksenhendler, David C. Fajgenbaum: International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 132(20): 2115-2124, 2018.

David C. Fajgenbaum: HHV-8-negative/idiopathic multicentric Castleman disease. UpToDate. 2018-Present. Notes: https://www.uptodate.com/contents/hhv-8-negative-idiopathic-multicentric-castleman-disease/

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Last updated: 03/29/2024
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