Donald L. Siegel, MD, PhD

Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
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
Member, Executive Committee, Dept of Pathology & Lab Med, University of Pennsylvania School of Medicine
Attending Physician, Division of Transfusion Med, Dept. Pathology & Lab Med, Hospital of the University of PA
Founding Director, Division of Transfusion Medicine & Therapeutic Pathology, Hospital of the University of PA
Member, Cell & Vaccine Production Facility Advisory Committee, University of Pennsylvania School of Medicine
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
Clinical/Research Fellowship in Transfusion Medicine
Division of Transfusion Medicine & Therapeutic Pathology
Search PubMed for articles
Center for Cellular Immunotherapies research lab
Clinical/Research Fellowship in Transfusion Medicine
Division of Transfusion Medicine & Therapeutic Pathology
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
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.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.
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.
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.
Jung, I.-Y., Noguera-Ortega, E., Bartoszek, R., Collins, S.M., Williams, E., Davis, M., Jadlowsky, J.K., Plesa, G., Siegel, D.L., Chew, A., Levine, B.L., Berger, S.L., Moon, E.K., Albelda, S.M., Fraietta, J.A.: Tissue-resident memory CAR T cells with stem-like characteristics display enhanced efficacy against solid and liquid tumors. Cell Reports Medicine 4: 101053, 2023.
Garfall, A., Cohen, A., Susanibar-Adaniya, S., Hwang, W.-T., Vogl, D., Waxman, A., Lacey, S., Gonzalez, V., Fraietta, J.A., Gupta, M., Kulikovskaya, I., Tian, L., Chen, F., Koterba, N., Bartoszek, R.L., Patchin, M., Xu, R., Plesa, G., Siegel, D.L., Brennan, A., Nelson, A.-M., Ferthio, R., Cosey, A., Shea, K.-M., Leskowitz, R., Four, M., Wilson, W., Miao, F., Lancaster, E., Carreno, B., Linette, G., Hexner, E., Young, R., Bu, D., Mansfield, K., Brogdon, J., June, C., Milone, M.C., Stadtmauer, E.: Anti-BCMA/CD19 CAR T Cells with early immunomodulatory maintenance for multiple myeloma responding to initial or later-line therapy. Blood Cancer Discovery 4: 118-133, 2023.
Yoshimoto, S., Chester, N., Xiong, A., Radaelli, E., Wang, H., Brillantes, M., Gulendran, G., Glassman, P., Siegel, D.L., Mason, N.J: Development and pharmacokinetic assessment of a fully canine anti-PD-1 monoclonal antibody for comparative translational research in dogs with spontaneous tumors. mAbs 15: e2004638-1 to e2004638-11, 2023.
Jung, I.-Y., Bartoszek, R.L., Rech, A., Collins, S.M., Ooi, S.-K., Williams, E.F., Hopkins, C., Narayan, V., Haas, N.B., Frey, N.V., Hexner, E.O., Siegel, D.L., Plesa, G., Porter, D.L., Cantu, A., Everett, J.K., Guedan, S., Berger, S.L., Bushman, F.D., Herbst, F., Fraietta, J.A.: Type I interferon signaling via the EGR2 transcriptional regulator potentiates CAR T cell-intrinsic dysfunction. Cancer Discovery 13: 1636-1655, 2023.