Donald L. Siegel, MD, PhD
Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Attending Physician, Blood Bank/Transfusion Medicine, Dept. Pathology & Lab Med, Hospital of the University of PA
Attending Physician, Dept. Pathology & Lab Med, Penn-Presbyterian Medical Center
Director, ACGME-accredited Fellowship Program in Blood Banking/Transfusion Medicine, Hospital of the University of PA
Medical Director, AABB-accredited Blood Bank and Apheresis Unit, Hospital of the University of Pennsylvania
Member for Oversight of Blood Usage, Clinical Effectiveness and Quality Improvement Committee, Hospital of the University of PA
Medical Director, FACT-accredited cell collection and processing facilities for Hematopoietic Stem Cell Transplant Program, Hospital of the University of Pennsylvania
Founding Director, Division of Transfusion Medicine & Therapeutic Pathology, Hospital of the University of PA
Director, Clinical Cell and Vaccine Production Facility, Center for Advanced Cellular Therapeutics, University of Pennsylvania School of Medicine
Department: Pathology and Laboratory Medicine
Contact information
9-112 South Tower, Big 421
3400 Civic Center Blvd
Philadelphia, PA 19104
3400 Civic Center Blvd
Philadelphia, PA 19104
Office: (215) 662-3942
Lab: (215) 898-9655
Lab: (215) 898-9655
Publications
Links
Search PubMed for articles
Center for Cellular Immunotherapies research lab
Division of Transfusion Medicine & Therapeutic Pathology
Clinical/Research Fellowship in Transfusion Medicine
Search PubMed for articles
Center for Cellular Immunotherapies research lab
Division of Transfusion Medicine & Therapeutic Pathology
Clinical/Research Fellowship in Transfusion Medicine
Education
Sc.B. (Biophysics)
Brown University, 1977.
Ph.D. (Biophysics)
Harvard University, 1983.
M.D.
University of Pennsylvania, 1987.
Permanent linkSc.B. (Biophysics)
Brown University, 1977.
Ph.D. (Biophysics)
Harvard University, 1983.
M.D.
University of Pennsylvania, 1987.
Description of Research Expertise
Research InterestsDiscovery 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.
Description of Clinical Expertise
transfusion medicine, blood banking, apheresis, hematopoietic stem cell collection/processing, cGMP manufacture of cellular therapies for phase I first-in-human clinical trialsSelected Publications
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.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.
93. Scholler, J., Song, A., Deshmukh, M., Song, D., Gabunia, K., Ji, M., Fan, T.J., June, C.H., Siegel, D.L.: Engineering a juxtamembrane-targeting CAR T-cell against mesothelin: A novel binder resilient to shed antigen for enhanced efficacy against ovarian and pancreatic cancer. Frontiers in Immunology 17:1805950, 2026.
Gu, M., Read, K., Bhardwaj, V., Carvalho, E., Nardo, D., Shayne, J., Shukla, D., Liu, W., Siegel, D.L., Sheppard, N., Milone, M., Cohen, A., Garfall, A., Riley, J.L.: Rab5 improves CAR T cell efficacy via reducing fratricide and maintaining surface CAR levels. Journal of Experimental Medicine 223 (6): e20252564, 2026.
Paruzzo, L. Chong, E.R., Chong, E.A., Zheng, Z., Guruprasad, P., Landsburg, D.J., Nasta, S.D., Stella, F., Ramasubramanian, R., de Souza, V.B., Alkhatib, M.H., Ho, M., Imparato, A., Chen, G.M., Siegel, D.L., Plesa, G., Dai, A., Mackey, S., Das, P., Michener, P., Jadlowsky, J., Bushman, F.D., Patel, V., Carturan, A., Napier, E.B., Gonzalez, V.E., Jarocha, D., Xu, R., Levine, B.L., Porazzi, P., Frey, N., Porter, D.L., Svoboda, J., Fraietta, J.A., June, C.H., Schuster, S.J., Ruella, M.: Decade-long persistence of CD19 CAR T-cells in B-cell lymphomas. Nature Medicine in press, 2026.
Noll, J.H., Dersh, D., Li, J.Y., Hemani, H., Lavorando, M., Bartoszek, R., Amses, K., Jain, A., Minehart, J., Ho, M., Ramirez-Fernandez, A., Paruzzo, L., Shestov, M., Camerini, E., Peters, Huang, X., Loren, A., Woyach, J., Goronzy, J., Kater, A.P., Ruella, M., Byrd, J., Powell, D., Gill S., Porter, D., Schuster, S., Bushman, F.D., Siegel, D.L., Levine, B.L., June, C.H., Frey, N., Cohen, A., Garfall, A., Long, M., Maus, M., Weng, N.-P., Diorio, C., Fraietta, J.A.: T-cell immunosenescence limits CD19 CAR T-cell function in chronic lymphocytic leukemia. Blood in press, 2026.
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(10.1038/s41551-026-01633-7), 2026.
Ramírez-Fernández, A., Bear, A., Kamali, E., Bartoszek, R., Ho, M., Chen, G., Dersh, D., Cordoba-Espejo, L., Liu, J., Deng, M., Velasco-Sidro, M., Jain, A., Noll, J.H., Hopkins, C., Koucky, O., Minehart, J., Dimitri, A., Williams, E., Lavorando, M., Segura-Tudela, A., Scholler, J., Barber-Rotenberg, J., Jadlowsky, J., Powell, D., Gonzalez, V., Siegel, D.L., Bruce Levine, B., Lotze, M., June, C., Riley, J., Vonderheide, R., Herbst, F., Fraietta, J.A.: A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection. J. Hematology Oncology in press, 2026.
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.
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.