David C. Fajgenbaum, MD, MBA, MSc

faculty photo
Assistant Professor of Medicine
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 714
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 Assistant 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.

An authority on cytokine storms and their treatment, Fajgenbaum launched the CORONA project in March 2020 to identify and track treatments for COVID-19. Today, CORONA is the world’s largest database of COVID-19 treatments, including 400+ medications that have been administered to 300,000+ patients, and a go-to resource for FDA, Google Health, and others. He serves on the treatment selection committee for the NIH’s ACTIV-6 trial as well as the Chair of the treatment selection committee for FDA/NIH/C-Path Institute’s CURE Drug Repurposing Collaboratory (CDRC) COVID-19 inpatient trial.

One of the youngest individuals ever appointed to the faculty at Penn Medicine and in the top 1 percent youngest awardees of an NIH R01 grant, Dr. Fajgenbaum leads over 20 translational research studies, including the CORONA project and a clinical trial of the drug that is saving his life. He has published scientific papers in high-impact journals such as the New England Journal of Medicine, Blood, and Journal of Clinical Investigation, including one paper selected by STAT News in 2020 as one of the best innovations in science and medicine.

Dr. Fajgenbaum co-founded the CDCN in 2012 to accelerate research and treatments for Castleman disease through a 'Collaborative Network Approach,' a business-inspired approach to biomedical research, which has become a blueprint for advancing rare disease research. He is also dedicated to advancing drug repurposing as co-director of the advisory committee for a FDA/NIH/C-Path public-private partnership called the CURE Drug Repurposing Collaboratory and lead investigator for a collaboration with the Chan Zuckerberg Initiative to advance rare disease drug repurposing. Dr. Fajgenbaum has been profiled in a cover story by The New York Times as well as by Good Morning America, CNN, Science, Reader's Digest, Forbes 30 Under 30, and the Today Show.

Dr. Fajgenbaum received 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. He studied for an MSc in Public Health from the University of Oxford as the 2007 Joseph L. Allbritton Scholar. Dr. Fajgenbaum earned his MD from the Raymond & Ruth Perelman School of Medicine at the University of Pennsylvania, where he was a 21st Century Gamble Scholar. He received his 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:
Patricia Tsao, MD, PhD, Director of Research
Sheila Pierson, MS, Associate Director of Clinical Research
Johnson Khor, Center/Registry Coordinator
Tori Powers, Data Analyst
Mark-Avery Tamakloe, Data Analyst
Alek Gorzewski, Data Analyst
Daniel Arenas, 2019-2020 Biomedical Leadership Fellow, MS3
Alexis Phillips, 2020-2021 Biomedical Leadership Fellow, MS3
Ruth-Anne Langan, Fourth year Immunology PhD student
Kunfeng Sun, PhD, Post-doctoral Fellow
Amber Cohen, Executive Administrator

The Center for Cytokine Storm Treatment & Laboratory and Fajgenbaum Lab is currently searching for multiple new roles. Visit https://www.med.upenn.edu/CSTL/job-opportunities.html for more information.

Selected Publications

Sheila K. Pierson, Aaron J. Stonestrom, Dustin Shilling, Jason Ruth, Christopher S. Nabel, Amrit Singh, Yue Ren, Katie Stone, Hongzhe Li, Frits van Rhee, David C. Fajgenbaum: Plasma proteomics identifies a 'chemokine storm' in idiopathic multicentric Castleman disease. American Journal of Hematology. 93(7): 902-912, 2018. Notes: identified a chemokine and cytokine storm in iMCD, CXCL13 as the most up-regulated protein, and lymph node stromal cells as the cellular source of CXCL13.

David C. Fajgenbaum & Dustin Shilling: Castleman Disease Pathogenesis. Chapter in: Hematology/Oncology Clinics of North America: Castleman’s Disease. Frits van Rhee, Nikhil C. Munshi (eds.). Elsevier, 32(1): 11-21, 2018.

Eric Oksenhendler, David Boutboul, David C. Fajgenbaum, Adrien Mirouse, Claire Fieschi, Marion Malphettes, Laetitia Vercellino, Veronique Meignin, Laurence Gerard, Lionel Galicier: The full spectrum of Castleman Disease: 273 patients studied over 20 years. British Journal of Hematology. 180(2): 206-216, 2018. Notes: contributed to the interpretation of clinical data analyses from the largest cohort of Castleman disease patients to date.

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. Notes: led panel and effort to establish the first-ever diagnostic criteria for iMCD.

Li Yu, Meifeng Tu, Jorge Cortes, Zijun Y. Xu-Monette, Roberto N. Miranda, Jun Zhang, Robert Z. Orlowski, Sattva Neelapu, Prajwal C. Boddu, Mary A. Akosile, Thomas S. Uldrick, Robert Yarchoan, L. Jeffrey Medeiros, Yong Li, David C. Fajgenbaum, Ken H. Young: Clinical and pathological characteristics of HIV- and HHV8- negative Castleman disease. Blood. 129(12): 1658-1668, 2017. Notes: largest study to date characterizing immunophenotypic and morphologic changes in tissue from iMCD patients.

Celine Louis, Sandrine Vijgen, Kaveh Samii, Yves Chalandon, Louis Terriou, David Launay, David C. Fajgenbaum, Jorg D. Seebach, Yannick D. Muller: TAFRO Syndrome in Caucasians: A Case Report and Review of the Literature. Frontiers in Medicine 4: 149, 2017 Notes: first study to characterize a cohort of TAFRO patients outside of Japan.

David C. Fajgenbaum, Jason R. Ruth, Dermot P. Kelleher, Arthur H. Rubenstein : The Collaborative Network Approach: A New Framework to Accelerate Castleman Disease and Other Rare Disease Research. The Lancet Haematology. 3(4): 150-152, 2016.

Noriko Iwaki, David C. Fajgenbaum, Christopher S. Nabel, Yuka Gion, Eisei Kondo, Mitsuhiro Kawano, Taro Masunari, Isao Yoshida, Hiroshi Moro, Koji Nikkuni, Kazue Takai, Kosei Matsue, Mitsutoshi Kurosawa, Masao Hagihara, Akio Saito, Masataka Okamoto, Kenji Yokota, Shinichiro Hiraiwa, Naoya Nakamura, Shinji Nakao, Tadashi Yoshino, Yasuharu Sato: Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. American Journal of Hematology. 91(2): 220-226, 2016. Notes: co-led analyses and interpretation of the data, which was the largest ever clinicopathologic analysis of the most deadly subtype of iMCD.

Amy Y. Liu, Christopher S. Nabel, Brian S. Finkelman, Jason R. Ruth, Razelle Kurzrock, Frits van Rhee, Vera P. Krymskaya, Dermot P. Kelleher, Arthur H. Rubenstein, David C. Fajgenbaum: Idiopathic Multicentric Castleman's Disease: A Systematic Literature Review. The Lancet Haematology. 3(4): 163-175, 2016. Notes: first study to uncover an association between iMCD and risk of malignancy which was also found to be associated with poor survival.

David C. Fajgenbaum, Frits van Rhee, Chris Nabel: HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 123(19): 2924-2933, 2014.

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Last updated: 01/22/2022
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