Donald L. Siegel, MD, PhD

faculty photo
Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Department: Pathology and Laboratory Medicine

Contact information
9-112 South Tower, Big 421
3400 Civic Center Blvd
Philadelphia, PA 19104
Office: (215) 662-3942
Lab: (215) 898-9655
Education:
Sc.B. (Biophysics)
Brown University, 1977.
Ph.D. (Biophysics)
Harvard University, 1983.
M.D.
University of Pennsylvania, 1987.
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Description of Research Expertise

Research Interests

Discovery and characterization of diagnostic and therapeutic monoclonal antibodies

Research Summary

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.

Selected Publications

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 2025.

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.

94. 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 epitope 806 and IL-13Rα2 in recurrent glioblastoma: a phase 1 dose finding study. Nature Medicine in press, 2025.

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.: Gene-targeted universal allogeneic gamma-delta CAR T cells for cancer immunotherapy. Nature Biomedical Engineering in press, 2025.

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 ImmunoTherapy Cancer in press, 2025.

Bhagwat, A.S., Torres, L., Shestova, O., Shestov, M., Mellors, P.W., Fisher, H.R., Farooki, S.N., Frost, B.F., Loken, M.R., Gaymon, A.L., , Frazee, D., Rogal, W., Frey, N., Hexner, E.O., Luger, S.M., Loren, A.W., Martin, M.E., McCurdy, S.R., Perl, A.E., Stadtmauer, E., Brogdon, J.L., Fraietta, J.A., Hwang, W.T., Siegel, D.L., Plesa, G., Aplenc, R., Porter, D.L., June, C.H., Gill, S.I.: Cytokine-mediated CAR T therapy resistance in AML. Nature Medicine 2024.

Bhagwat, A.S., Torres, L., Shestova, O., Shestov, M., Mellors, P.W., Fisher, H.R., Farooki, S.N., Frost, B.F., Loken, M.R., Gaymon, A.L., , Frazee, D., Rogal, W., Frey, N., Hexner, E.O., Luger, S.M., Loren, A.W., Martin, M.E., McCurdy, S.R., Perl, A.E., Stadtmauer, E., Brogdon, J.L., Fraietta, J.A., Hwang, W.T., Siegel, D.L., Plesa, G., Aplenc, R., Porter, D.L., June, C.H., Gill, S.I.: Cytokine-mediated CAR T therapy resistance in AML. Nature Medicine( ), 2024 Notes: doi.org/10.1038/s41591-024-03271-5

Mack, E.A., Dougher, M.C., Ginda, A., Cahill, C., Murter, M., Schell, K., Tanhehco, Y.C., Siegel, D.L., Bhoj, V., Fesnak, A.D., Kambayashi, T., Aqui, N., O’Doherty, U.: Red cell exchange for rapid leukoreduction in adults with hyperleukocytosis and leukostasis. Blood 143: 1049-1054, 2024.

Logun, M., Wang, X., Sun, Y., Bagley, S.J., Li, N., Desai, A., Zhang, D.Y., Nasrallah, M.P., Pai, E. L.-L., Oner, B.S., Plesa, G., Siegel, D.L., Binder, Z.A., Ming, G-I, Song, H., O'Rourke, D.M.: Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy. Cell Stem Cell 32:: 1-10, 2024.

Bagley, S.J., Logun, M., Fraietta, J.A., Wang, X., Desai, A.S., Bagley, L.J., Nabavizadeh, A., Jarocha, D., Martins, R., Maloney, E., Lledo, L., Stein, C., Marshall, A., Leskowitz, R., Jadlowsky, J.K., Christensen, S., Oner, B.S., Plesa, G., Brennan, A., Gonzalez, V., Chen, F., Sun, Y., Gladney, W., Barrett, D., Nasrallah, M.P., Hwang, W.-T., Ming, G.-L., Song, H., Siegel, D.L., June, C.H., Hexner, E.O., Binder, Z.A., O'Rourke, D.M.: Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: Phase 1 trial interim results. Nature Medicine 30: 1320-1329, 2024.

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Last updated: 05/14/2025
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