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Donald L. Siegel, MD, PhD
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Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
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Attending Physician, Blood Bank/Transfusion Medicine, Dept. Pathology & Lab Med, Hospital of the University of PA
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Attending Physician, Dept. Pathology & Lab Med, Penn-Presbyterian Medical Center
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Director, ACGME-accredited Fellowship Program in Blood Banking/Transfusion Medicine, Hospital of the University of PA
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Medical Director, AABB-accredited Blood Bank and Apheresis Unit, Hospital of the University of Pennsylvania
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Member for Oversight of Blood Usage, Clinical Effectiveness and Quality Improvement Committee, Hospital of the University of PA
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Medical Director, FACT-accredited cell collection and processing facilities for Hematopoietic Stem Cell Transplant Program, Hospital of the University of Pennsylvania
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Founding Director, Division of Transfusion Medicine & Therapeutic Pathology, Hospital of the University of PA
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Director, Clinical Cell and Vaccine Production Facility, Center for Advanced Cellular Therapeutics, University of Pennsylvania School of Medicine
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Department: Pathology and Laboratory Medicine
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Contact information
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9-112 South Tower, Big 421
39 3400 Civic Center Blvd
Philadelphia, PA 19104
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39 3400 Civic Center Blvd
Philadelphia, PA 19104
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Office: (215) 662-3942
40 Lab: (215) 898-9655
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40 Lab: (215) 898-9655
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Publications
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Links
99 Search PubMed for articles
c4 Division of Transfusion Medicine & Therapeutic Pathology
83 Center for Cellular Immunotherapies research lab
b2 Clinical/Research Fellowship in Transfusion Medicine
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99 Search PubMed for articles
c4 Division of Transfusion Medicine & Therapeutic Pathology
83 Center for Cellular Immunotherapies research lab
b2 Clinical/Research Fellowship in Transfusion Medicine
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Education:
21 a Sc.B. 17 (Biophysics) c
29 Brown University, 1977.
21 a Ph.D. 17 (Biophysics) c
2b Harvard University, 1983.
21 9 M.D. c
33 University of Pennsylvania, 1987.
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Permanent link21 a Sc.B. 17 (Biophysics) c
29 Brown University, 1977.
21 a Ph.D. 17 (Biophysics) c
2b Harvard University, 1983.
21 9 M.D. c
33 University of Pennsylvania, 1987.
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5a Discovery and characterization of diagnostic and therapeutic monoclonal antibodies
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19 Research Summary
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2b2 My laboratory studies human immune repertoires in health and disease using phage display technologies for the production of human and non-human monoclonal antibodies relevant to transfusion medicine, benign hematology, infectious diseases, and oncology. Current studies focus on developing targeted drug delivery methods using red cell antibodies coupled to novel anti-thrombotic/anti-inflammatory molecules; cloning monoclonal primate neutralizing Dengue, Ebola, MERS and Zika virus antibodies for human in vivo antibody gene expression therapy; and isolating recombinant human and humanized antibody fragments for the design of T-cell chimeric antigen receptors for cancer therapy.
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Description of Research Expertise
23 Research Interests8
5a Discovery and characterization of diagnostic and therapeutic monoclonal antibodies
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19 Research Summary
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2b2 My laboratory studies human immune repertoires in health and disease using phage display technologies for the production of human and non-human monoclonal antibodies relevant to transfusion medicine, benign hematology, infectious diseases, and oncology. Current studies focus on developing targeted drug delivery methods using red cell antibodies coupled to novel anti-thrombotic/anti-inflammatory molecules; cloning monoclonal primate neutralizing Dengue, Ebola, MERS and Zika virus antibodies for human in vivo antibody gene expression therapy; and isolating recombinant human and humanized antibody fragments for the design of T-cell chimeric antigen receptors for cancer therapy.
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Description of Clinical Expertise
c0 transfusion medicine, blood banking, apheresis, hematopoietic stem cell collection/processing, cGMP manufacture of cellular therapies for phase I first-in-human clinical trials1a 29
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27c Barber-Rotenberg, J.S., Haas, A.R., Aggarwal, C., O'Hara, M.H., Hexner, E., Pequignot, E., Dowd, E., Ndeupen, S., Thai, E., Chen, F., Oner, B.S., Czuczman, C., Gonzalez, V.E., Fraietta, J.A., Hwang, W.-T., Chew, A., Jadlowsky, J.K., Marshall, A., Shea, K.-M., Jiang, Y., Cosey, A., Ferthio, R., Plesa, G., Siegel, D.L., Young, R.M., Sheppard, N.C., Albelda, S.M., June, C.H., Tanyi, J.L.: Phase I study of autologous T cells bearing fully human chimeric antigen receptors targeting mesothelin in mesothelin-expressing cancers. Molecular Therapy in press, 2026.
47d Jadlowsky, J.K., Hexner, E.O., Marshall, A., Grupp, S.A., Frey, N.V., Riley, J.L., Veloso, E., McConville, H., Rogal, W., Czuczman, C., Hwang, W.-T., Li, Y., Leskowitz, R.M., Farrelly, O., Karar, J., Christensen, S., Barber-Rotenberg, J., Gaymon, A., Aronson, N., Bernstein, W., Melenhorst, J.J., Roche, A.M., Everett, J.K., Zolnoski, S.A., McFarland, A.G., Reddy, S., Petrichenko, A., Cook, E.J., Lee, C., Gonzalez, V.E., Alexander, K., Kulikovskaya, I., Ramírez-Fernández, A., Minehart, J.C., Ruella, M., Gill, S.I., Schuster, S.J., Cohen, A.D., Garfall, A.L., Shah, P.D., Porter, D.L., Maude, S.L., Levine, B.L., Siegel, D.L., Chew, A., McKenna, S., Lledo, L., Davis, M.M, Plesa, G., Herbst, F., Stadtmauer, E.A., Tebas, P., DiNofia, A., Haas, A., Haas, N.B., Myers, R., O’Rourke, D.M., Svoboda, J., Tanyi, J.L., Aplenc, R., Jacobson, J.M., Ko, A.H., Cohen, R.B., June, C.H., Bushman, F.D., Fraietta, J.A.: Long-term safety analysis in 783 patients treated with lentiviral or gammaretroviral gene-modified T-cells. Nature Medicine doi.10.1038/s41591-024-03478-6, 2025.
168 Bloch, E.M., Triulzi, D., Sachais, B.S., Hod, E.A., Cushing, M., Jacobs, J.W., Tobian, A.A.R., Shan, H., Leonard N. Chen, L.N., McGonigle, A.M., Tormey, C.A., Szczepiorkowski, Z.M., Siegel, D.L.: The incompatible match for transfusion medicine fellowships. Transfusion 65: 246-248, 2025.
2d7 Chen, G.M., Gering, D., Satulovsky, J., Datta, S., Lai, P., Karar, J., Gonzalez, V.E., Alexander, K., Chew, A., Jadlowsky, J.K., Ruella, M., Paruzzo, L., Amses, K.R., Rech, A.J., Stadtmauer, E.A., Frey, N.V., Hexner, E.O., Porter, D.L., Cohen, A.D., Gill, S.I., Garfall, A.L., Schuster, S.J., Mo, K.C., Liang, S.I., Spasic, M., Levine, B.L., Siegel, D.L., Ramírez- Fernández, A., Mackall, C.L., Bushman, F.D., Good, Z., E. John Wherry, E.J., June, C.H., Jain, A., Cabanski, C., Fraietta, J.A.: Predictive biomarkers of response to chimeric antigen receptor (CAR) T-cell therapy for pan-hematologic cancer. Nature Biomedical Engineering in press, 2025.
273 Svoboda, J., Landsburg, D.J., Gerson, J., Nasta, S.D., Barta, S.K., Chong, E.A., Cook, M., Frey, N.V., Shea, J., Cervini, A., Marshall, A., Four, M., Davis, M.M., Jadlowski, J.K., Chew, A., Pequignot, E., Gonzalez, V., Noll, J.H., Paruzzo, L., Rojas-Levine, J., Plesa, G., Schollar, J., Siegel, D.L., Levine, B., Porter, D.L., Ghassemi, S., Ruella, M., Rech, A., Leskowitz, R.M., Fraietta, J.A., Hwang, W.-T., Hexner, E., Schuster, S.J., June, C.H.: Enhanced CAR T-cell therapy for lymphoma after previous failure. New England J Med 392: 1824-1835, 2025.
305 Bagley, S.J., Desai, A.S., Fraietta, J.A., Silverbush, D., Chafamo, D., Freeburg, N.F., Gopikrishna, G.K., Rech, A.J., Nabavizadeh, A., Bagley, L.J., Park, J., Jarocha, D., Martins, R., Sarmiento, N., Maloney, E., Lledo, L., Stein, C., Marshall, A., Leskowitz, R.M., Jadlowsky, J.K., Mackey, S., Christensen, S., Oner, B.S., Plesa, G., Brennan, A., Gonzalez, V. Chen, F., Barrett, D., Colbourn, R., Nasrallah, M.P., Mourelatos, Z., Hwang, W.-T., Alanio, C., Siegel, D.L., June, C.H., Hexner, E.O., Binder, Z.A., O'Rourke, D.M.: Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial. Nature Medicine doi/10.1038/s41591-025-03745-0, 2025.
24b Ramirez-Fernández, A., Dimitri, A., Chen, F., Bartoszek, R., Chen, G., Córdoba-Espejo, L., Zhou, Y., Tang, Y.H., Lin, C.-T., Acosta, R., Scholler, J., Ghilardi, G., Porazzi, P., Pellicer, M., Profitós-Pelejà, N., Barta, S., Chew, A., Jadlowsky, J., Vanessa Gonzalez, V., Siegel, D.L., Levine, B., Roué, G., Ruella, M., Lotze, M., June, C.H., Riley, J., Fraietta, J.: CCR5-targeted allogeneic gamma-delta CD19 CAR T cells for HIV-associated B cell malignancy immunotherapy. Nature Biomedical Engineering 2025.
2a9 Myers, R.M., DiNofia, A.M., Li, Y., Diorio, C., Liu, H., Wertheim, G., Fraietta, J.A., Gonzalez, V., Plesa, G., Siegel, D.L., Iannone, E., Shinehouse, L., Brogdon, J.L., Taylor, C., Jadlowsky, J.K., Hexner, E.O., Engels, B., Baniewicz, D., Callahan, C., Ruella, M., Aplenc, R., Leahy, A.B., McClory, S.E., Rheingold, S.R., Wray, L., June, C.H., Maude, S.L., Frey, N.V., Grupp, S.A.: CD22-targeted chimeric antigen receptor-modified T cells for children and adults with relapse of B-cell acute lymphoblastic leukemia after CD19-directed immunotherapy. J Immunoherapy Cancer doi:10.1136/jitc-2025-011549, 2025.
27b Aznar, M.A., Good, C.R., Barber-Rotenberg, J.S., Agarwal, S., Wilson, W., Watts, A., Zhang, Z., Gonzales, D., Donahue, G., Hwang, W.-T., Rennels, A.K., Rech, A.J., Kuramitsu, S., Glastad, K.M., Alexander, K.A., Plesa, G., Brennan, A., Siegel, D.L., Tanyi, J., Haas, A., Drew Torigian, D., Nadolski, G., Gonzalez, V.E., Hexner, E.O., Fraietta, J.A., Jadlowsky, J.K., Young, R.M., Berger, S.L., June, C.H., O’Hara, M.H.: Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer. Cell Reports Medicine doi/10.1016/j.xcrm.2025.102301, 2025.
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Selected Publications
288 Bhoj, V.G., Kaminski, M., Zhao, H., Jackson, K., Montgomery, R.A., Ali, N., Mangiola, M., Spitzer, T.R., Safa, K., Pattanayak, V., Taj, R., Joy Chiu, J., Bui, T.-M., Sonnenberg, E.M., Markmann, J.F., Milone, M.C., June, C.H., Siegel, D.L., Fraietta, J.A., Gonzalez, V., Locci, M., Palmer, M., Monos, D., Hwang, W.-T .Sledge, T., Bridges, N.D., Goldstein, J.S., Odim, J., Sweet, S.C., Besharatian, B.D., Hussain, S.M., Brown, N.K., Kamoun, M., Garfall, A.L., Naji, A.: Kidney transplant in two highly-sensitized candidates post-CAR T cell therapy. N Engl J Med in press, 2026.27c Barber-Rotenberg, J.S., Haas, A.R., Aggarwal, C., O'Hara, M.H., Hexner, E., Pequignot, E., Dowd, E., Ndeupen, S., Thai, E., Chen, F., Oner, B.S., Czuczman, C., Gonzalez, V.E., Fraietta, J.A., Hwang, W.-T., Chew, A., Jadlowsky, J.K., Marshall, A., Shea, K.-M., Jiang, Y., Cosey, A., Ferthio, R., Plesa, G., Siegel, D.L., Young, R.M., Sheppard, N.C., Albelda, S.M., June, C.H., Tanyi, J.L.: Phase I study of autologous T cells bearing fully human chimeric antigen receptors targeting mesothelin in mesothelin-expressing cancers. Molecular Therapy in press, 2026.
47d Jadlowsky, J.K., Hexner, E.O., Marshall, A., Grupp, S.A., Frey, N.V., Riley, J.L., Veloso, E., McConville, H., Rogal, W., Czuczman, C., Hwang, W.-T., Li, Y., Leskowitz, R.M., Farrelly, O., Karar, J., Christensen, S., Barber-Rotenberg, J., Gaymon, A., Aronson, N., Bernstein, W., Melenhorst, J.J., Roche, A.M., Everett, J.K., Zolnoski, S.A., McFarland, A.G., Reddy, S., Petrichenko, A., Cook, E.J., Lee, C., Gonzalez, V.E., Alexander, K., Kulikovskaya, I., Ramírez-Fernández, A., Minehart, J.C., Ruella, M., Gill, S.I., Schuster, S.J., Cohen, A.D., Garfall, A.L., Shah, P.D., Porter, D.L., Maude, S.L., Levine, B.L., Siegel, D.L., Chew, A., McKenna, S., Lledo, L., Davis, M.M, Plesa, G., Herbst, F., Stadtmauer, E.A., Tebas, P., DiNofia, A., Haas, A., Haas, N.B., Myers, R., O’Rourke, D.M., Svoboda, J., Tanyi, J.L., Aplenc, R., Jacobson, J.M., Ko, A.H., Cohen, R.B., June, C.H., Bushman, F.D., Fraietta, J.A.: Long-term safety analysis in 783 patients treated with lentiviral or gammaretroviral gene-modified T-cells. Nature Medicine doi.10.1038/s41591-024-03478-6, 2025.
168 Bloch, E.M., Triulzi, D., Sachais, B.S., Hod, E.A., Cushing, M., Jacobs, J.W., Tobian, A.A.R., Shan, H., Leonard N. Chen, L.N., McGonigle, A.M., Tormey, C.A., Szczepiorkowski, Z.M., Siegel, D.L.: The incompatible match for transfusion medicine fellowships. Transfusion 65: 246-248, 2025.
2d7 Chen, G.M., Gering, D., Satulovsky, J., Datta, S., Lai, P., Karar, J., Gonzalez, V.E., Alexander, K., Chew, A., Jadlowsky, J.K., Ruella, M., Paruzzo, L., Amses, K.R., Rech, A.J., Stadtmauer, E.A., Frey, N.V., Hexner, E.O., Porter, D.L., Cohen, A.D., Gill, S.I., Garfall, A.L., Schuster, S.J., Mo, K.C., Liang, S.I., Spasic, M., Levine, B.L., Siegel, D.L., Ramírez- Fernández, A., Mackall, C.L., Bushman, F.D., Good, Z., E. John Wherry, E.J., June, C.H., Jain, A., Cabanski, C., Fraietta, J.A.: Predictive biomarkers of response to chimeric antigen receptor (CAR) T-cell therapy for pan-hematologic cancer. Nature Biomedical Engineering in press, 2025.
273 Svoboda, J., Landsburg, D.J., Gerson, J., Nasta, S.D., Barta, S.K., Chong, E.A., Cook, M., Frey, N.V., Shea, J., Cervini, A., Marshall, A., Four, M., Davis, M.M., Jadlowski, J.K., Chew, A., Pequignot, E., Gonzalez, V., Noll, J.H., Paruzzo, L., Rojas-Levine, J., Plesa, G., Schollar, J., Siegel, D.L., Levine, B., Porter, D.L., Ghassemi, S., Ruella, M., Rech, A., Leskowitz, R.M., Fraietta, J.A., Hwang, W.-T., Hexner, E., Schuster, S.J., June, C.H.: Enhanced CAR T-cell therapy for lymphoma after previous failure. New England J Med 392: 1824-1835, 2025.
305 Bagley, S.J., Desai, A.S., Fraietta, J.A., Silverbush, D., Chafamo, D., Freeburg, N.F., Gopikrishna, G.K., Rech, A.J., Nabavizadeh, A., Bagley, L.J., Park, J., Jarocha, D., Martins, R., Sarmiento, N., Maloney, E., Lledo, L., Stein, C., Marshall, A., Leskowitz, R.M., Jadlowsky, J.K., Mackey, S., Christensen, S., Oner, B.S., Plesa, G., Brennan, A., Gonzalez, V. Chen, F., Barrett, D., Colbourn, R., Nasrallah, M.P., Mourelatos, Z., Hwang, W.-T., Alanio, C., Siegel, D.L., June, C.H., Hexner, E.O., Binder, Z.A., O'Rourke, D.M.: Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial. Nature Medicine doi/10.1038/s41591-025-03745-0, 2025.
24b Ramirez-Fernández, A., Dimitri, A., Chen, F., Bartoszek, R., Chen, G., Córdoba-Espejo, L., Zhou, Y., Tang, Y.H., Lin, C.-T., Acosta, R., Scholler, J., Ghilardi, G., Porazzi, P., Pellicer, M., Profitós-Pelejà, N., Barta, S., Chew, A., Jadlowsky, J., Vanessa Gonzalez, V., Siegel, D.L., Levine, B., Roué, G., Ruella, M., Lotze, M., June, C.H., Riley, J., Fraietta, J.: CCR5-targeted allogeneic gamma-delta CD19 CAR T cells for HIV-associated B cell malignancy immunotherapy. Nature Biomedical Engineering 2025.
2a9 Myers, R.M., DiNofia, A.M., Li, Y., Diorio, C., Liu, H., Wertheim, G., Fraietta, J.A., Gonzalez, V., Plesa, G., Siegel, D.L., Iannone, E., Shinehouse, L., Brogdon, J.L., Taylor, C., Jadlowsky, J.K., Hexner, E.O., Engels, B., Baniewicz, D., Callahan, C., Ruella, M., Aplenc, R., Leahy, A.B., McClory, S.E., Rheingold, S.R., Wray, L., June, C.H., Maude, S.L., Frey, N.V., Grupp, S.A.: CD22-targeted chimeric antigen receptor-modified T cells for children and adults with relapse of B-cell acute lymphoblastic leukemia after CD19-directed immunotherapy. J Immunoherapy Cancer doi:10.1136/jitc-2025-011549, 2025.
27b Aznar, M.A., Good, C.R., Barber-Rotenberg, J.S., Agarwal, S., Wilson, W., Watts, A., Zhang, Z., Gonzales, D., Donahue, G., Hwang, W.-T., Rennels, A.K., Rech, A.J., Kuramitsu, S., Glastad, K.M., Alexander, K.A., Plesa, G., Brennan, A., Siegel, D.L., Tanyi, J., Haas, A., Drew Torigian, D., Nadolski, G., Gonzalez, V.E., Hexner, E.O., Fraietta, J.A., Jadlowsky, J.K., Young, R.M., Berger, S.L., June, C.H., O’Hara, M.H.: Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer. Cell Reports Medicine doi/10.1016/j.xcrm.2025.102301, 2025.
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