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David C. Fajgenbaum, MD, MBA, MSc
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Associate Professor of Medicine (Translational Medicine and Human Genetics)
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Department: Medicine
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Graduate Group Affiliations
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- Immunology e
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Contact information
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David C. Fajgenbaum
3f University of Pennsylvania, Perelman School of Medicine
3b Division of Translational Medicine & Human Genetics
3f Center for Cytokine Storm Treatment & Laboratory (CSTL)
1b 3535 Market Street
36 Suite 700, Room 717
Philadelphia, PA 19104
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3f University of Pennsylvania, Perelman School of Medicine
3b Division of Translational Medicine & Human Genetics
3f Center for Cytokine Storm Treatment & Laboratory (CSTL)
1b 3535 Market Street
36 Suite 700, Room 717
Philadelphia, PA 19104
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Fax: 877-991-9674
32 Lab: 215-614-0935
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32 Lab: 215-614-0935
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Email:
cstl@pennmedicine.upenn.edu
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cstl@pennmedicine.upenn.edu
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Publications
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Links
b5 Search PubMed for articles
b5 "Chasing My Cure: A Doctor's Race to Turn Hope Into Action;" A Memoir
73 For More Information About My Work & Mission
4b Every Cure
65 Castleman Disease Collaborative Network
81 Center for Cytokine Storm Treatment & Laboratory (CSTL)
6e Twitter handle: @DavidFajgenbaum
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b5 Search PubMed for articles
b5 "Chasing My Cure: A Doctor's Race to Turn Hope Into Action;" A Memoir
73 For More Information About My Work & Mission
4b Every Cure
65 Castleman Disease Collaborative Network
81 Center for Cytokine Storm Treatment & Laboratory (CSTL)
6e Twitter handle: @DavidFajgenbaum
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Education:
21 7 BS 44 (Honors Human Sciences with Distinction, Magna Cum Laude) c
3e Georgetown University, Washington, DC, 2007.
21 8 MSc 1a (Public Health) c
39 University of Oxford, Oxford, UK, 2008.
21 7 MD 15 (Medicine) c
4f University of Pennsylvania Perelman School of Medicine, 2013.
21 8 MBA 2b (Health Care Management Program) c
4f Wharton School of Business, University of Pennsylvania, 2015.
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Permanent link21 7 BS 44 (Honors Human Sciences with Distinction, Magna Cum Laude) c
3e Georgetown University, Washington, DC, 2007.
21 8 MSc 1a (Public Health) c
39 University of Oxford, Oxford, UK, 2008.
21 7 MD 15 (Medicine) c
4f University of Pennsylvania Perelman School of Medicine, 2013.
21 8 MBA 2b (Health Care Management Program) c
4f Wharton School of Business, University of Pennsylvania, 2015.
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1b Research interests:
181 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
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11 Keywords:
51 IL-6, cytokine storm, stromal cells; chemokines, PI3K/Akt/mTOR, JAK/STAT3
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19 Research summary:
c1 1) Elucidating the etiology, dysregulated cell types, signaling pathways, and effector cytokines in idiopathic multicentric Castleman disease (iMCD) and related cytokine storm disorders
245 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.
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3d 2) Identifying effective treatments for iMCD patients
1b1 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.
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37 3) PI3K/Akt/mTOR and JAK/STAT signaling in iMCD
480 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.
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49 4) Investigating the role of stromal cells and chemokines in iMCD
2dd 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.
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33 Rotation Projects are available in all areas
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Description of Research Expertise
4a See https://www.med.upenn.edu/CSTL/ for more information.8
1b Research interests:
181 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
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11 Keywords:
51 IL-6, cytokine storm, stromal cells; chemokines, PI3K/Akt/mTOR, JAK/STAT3
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19 Research summary:
c1 1) Elucidating the etiology, dysregulated cell types, signaling pathways, and effector cytokines in idiopathic multicentric Castleman disease (iMCD) and related cytokine storm disorders
245 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.
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3d 2) Identifying effective treatments for iMCD patients
1b1 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.
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37 3) PI3K/Akt/mTOR and JAK/STAT signaling in iMCD
480 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.
8
49 4) Investigating the role of stromal cells and chemokines in iMCD
2dd 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.
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33 Rotation Projects are available in all areas
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20d Mizuna Otsuka, Tomohiro Koga, Remi Sumiyoshi, Shoichi Fukui, Yuko Kaneko, Takayuki Shimizu, Atsushi Katsube, Shingo Yano, Yasufumi Masaki, Makoto Ide, Hajime Yoshifuji, Masayasu Kitano, Yasuharu Sato, Naoki Sawa, Hiroaki Niiro, Naoya Nakamura, David C. Fajgenbaum, Frits van Rhee, Atsushi Kawakami: Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns. American Journal of Hematology. 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 32 2025 (online ahead of print).
218 Allan Feng, Michael V. Gonzalez, Muge Kalaycioglu, Xihui Yin, Melanie D. Mumau, Saishravan Shyamsundar, Mateo Bustamante Sarmiento, Sarah E. Chang, Dhingra Shaurya, Tea Dodig-Crnkovic, Jochen M. Schwenk, Tarun Garg, Kazuyuki Yoshizaki, Frits van Rhee, David C. Fajgenbaum, Paul J. Utz: Common connective tissue disorder and anti-cytokine autoantibodies are enriched in idiopathic multicentric castleman disease patients. Frontiers in Immunology 16(1528465), 2025.
177 Ira D. Miller, Melanie D. Mumau, Saishravan Shyamsundar, Mateo Sarmiento Bustamante, Pedro Horna, Michael V. Gonzalez, David C. Fajgenbaum: No evidence for active viral infection in unicentric and idiopathic multicentric Castleman disease by Viral-Track analysis. Scientific Reports. 15(1): 1676, 2025.
189 Melanie D. Mumau, Michael V. Gonzalez, Chunyu Ma, Abiola H. Irvine, Mateo Sarmiento Bustamante, Saishravan Shyamsundar, Luke Y.C. Chen, David Koslicki, David C. Fajgenbaum: Identifying and Targeting TNF Signaling in Idiopathic Multicentric Castleman's Disease. The New England Journal of Medicine. 392(6): 616-618, 2025.
254 Asami Nishikori, Midori Filiz Nishimura, David C. Fajgenbaum, Yoshito Nishimura, Kanna Maehama, Tomoka Haratake, Tetsuya Tabata, Mitsuhiro Kawano, Naoya Nakamura, Shuji Momose, Remi Sumiyoshi, Tomohiro Koga, Hidetaka Yamamoto, Frits van Rhee, Atsushi Kawakami, Yasuharu Sato: Diagnostic challenges of the idiopathic plasmacytic lymphadenopathy (IPL) subtype of idiopathic multicentric Castleman disease (iMCD): Factors to differentiate from IgG4-related disease. Journal of Clinical Pathology. 2024 (online ahead of print).
1b0 Marley Blommers, Sorin Selegean, Richard K Wood, Mateo Sarmiento Bustamante, Saishravan Shyamsundar, E. Ashley Wiley, Emilie Comeau, Allam A. Shawwa, Stefan Rose-John, David C. Fajgenbaum, Luke Y. C. Chen.: Idiopathic multicentric Castleman disease with marrow fibrosis and extramedullary hematopoiesis. European Journal of Haematology. 113(6): 833-841, 2024.
119 Gordan Srkalovic, Sally Nijim, Maya Blanka Srkalovic, David C. Fajgenbaum: Increase in Vascular Endothelial Growth Factor (VEGF) Expression and the Pathogenesis of iMCD-TAFRO. Biomedicines. 12(6): 1328, 2024.
1a1 Madelaine Beckett, Caroline Spaner, Mariam Goubran, John Wade, Juan Antonio Avina-Zubieta, Audi Setiadi, Lori Tucker, Kam Shojania, Sheila Au, Andre Mattman, Agnes Y. Y. Lee, David C. Fajgenbaum, Luke Y. C. Chen: CRP and sCD25 help distinguish between adult-onset Still's disease and HLH. European Journal of Haematology. 113(5): 576-583, 2024.
e8 Christian Hoffmann, Eric Oksenhendler, Sarah Littler, Lisa Grant, Karan Kanhai, David C. Fajgenbaum: The clinical picture of Castleman disease: a systematic review and meta-analysis 40 Blood Advances. 8(18): 4924-4935, 2024.
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Selected Publications
228 Sheila K. Pierson, Joshua D. Brandstadter, Drew Torigian, Adam Bagg, Mary Jo Lechowicz, Daisy Alapat, Corey Casper, Amy Chadburn, Shanmuganathan Chandrakasan, Angela Dispenzieri, Alexander Fossa, Christian Hoffmann, Makoto Ide, Razelle Kurzrock, Sudipto Mukherjee, Sunita D. Nasta, José-Tomás Navarro, Ariela Noy, Eric Oksenhendler, Mateo Sarmiento Bustamante, Saishravan Shyamsundar, Matthew J. Streetly, Raymond Siu Ming Wong, Lu Zhang, Megan S. Lim, Gordan Srkalovic, Frits van Rhee, David C. Fajgenbaum c5 : Characterizing the heterogeneity of Castleman disease and oligocentric subtype: Findings from the ACCELERATE registry. Blood Advances. 2025 (online ahead of print).20d Mizuna Otsuka, Tomohiro Koga, Remi Sumiyoshi, Shoichi Fukui, Yuko Kaneko, Takayuki Shimizu, Atsushi Katsube, Shingo Yano, Yasufumi Masaki, Makoto Ide, Hajime Yoshifuji, Masayasu Kitano, Yasuharu Sato, Naoki Sawa, Hiroaki Niiro, Naoya Nakamura, David C. Fajgenbaum, Frits van Rhee, Atsushi Kawakami: Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns. American Journal of Hematology. 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 32 2025 (online ahead of print).
218 Allan Feng, Michael V. Gonzalez, Muge Kalaycioglu, Xihui Yin, Melanie D. Mumau, Saishravan Shyamsundar, Mateo Bustamante Sarmiento, Sarah E. Chang, Dhingra Shaurya, Tea Dodig-Crnkovic, Jochen M. Schwenk, Tarun Garg, Kazuyuki Yoshizaki, Frits van Rhee, David C. Fajgenbaum, Paul J. Utz: Common connective tissue disorder and anti-cytokine autoantibodies are enriched in idiopathic multicentric castleman disease patients. Frontiers in Immunology 16(1528465), 2025.
177 Ira D. Miller, Melanie D. Mumau, Saishravan Shyamsundar, Mateo Sarmiento Bustamante, Pedro Horna, Michael V. Gonzalez, David C. Fajgenbaum: No evidence for active viral infection in unicentric and idiopathic multicentric Castleman disease by Viral-Track analysis. Scientific Reports. 15(1): 1676, 2025.
189 Melanie D. Mumau, Michael V. Gonzalez, Chunyu Ma, Abiola H. Irvine, Mateo Sarmiento Bustamante, Saishravan Shyamsundar, Luke Y.C. Chen, David Koslicki, David C. Fajgenbaum: Identifying and Targeting TNF Signaling in Idiopathic Multicentric Castleman's Disease. The New England Journal of Medicine. 392(6): 616-618, 2025.
254 Asami Nishikori, Midori Filiz Nishimura, David C. Fajgenbaum, Yoshito Nishimura, Kanna Maehama, Tomoka Haratake, Tetsuya Tabata, Mitsuhiro Kawano, Naoya Nakamura, Shuji Momose, Remi Sumiyoshi, Tomohiro Koga, Hidetaka Yamamoto, Frits van Rhee, Atsushi Kawakami, Yasuharu Sato: Diagnostic challenges of the idiopathic plasmacytic lymphadenopathy (IPL) subtype of idiopathic multicentric Castleman disease (iMCD): Factors to differentiate from IgG4-related disease. Journal of Clinical Pathology. 2024 (online ahead of print).
1b0 Marley Blommers, Sorin Selegean, Richard K Wood, Mateo Sarmiento Bustamante, Saishravan Shyamsundar, E. Ashley Wiley, Emilie Comeau, Allam A. Shawwa, Stefan Rose-John, David C. Fajgenbaum, Luke Y. C. Chen.: Idiopathic multicentric Castleman disease with marrow fibrosis and extramedullary hematopoiesis. European Journal of Haematology. 113(6): 833-841, 2024.
119 Gordan Srkalovic, Sally Nijim, Maya Blanka Srkalovic, David C. Fajgenbaum: Increase in Vascular Endothelial Growth Factor (VEGF) Expression and the Pathogenesis of iMCD-TAFRO. Biomedicines. 12(6): 1328, 2024.
1a1 Madelaine Beckett, Caroline Spaner, Mariam Goubran, John Wade, Juan Antonio Avina-Zubieta, Audi Setiadi, Lori Tucker, Kam Shojania, Sheila Au, Andre Mattman, Agnes Y. Y. Lee, David C. Fajgenbaum, Luke Y. C. Chen: CRP and sCD25 help distinguish between adult-onset Still's disease and HLH. European Journal of Haematology. 113(5): 576-583, 2024.
e8 Christian Hoffmann, Eric Oksenhendler, Sarah Littler, Lisa Grant, Karan Kanhai, David C. Fajgenbaum: The clinical picture of Castleman disease: a systematic review and meta-analysis 40 Blood Advances. 8(18): 4924-4935, 2024.
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