Donald L. Siegel, PhD, MD
Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Director, Division of Transfusion Medicine and Therapeutic Pathology
Director, Fellowship Program in Transfusion Medicine
Director, Clinical Cell and Vaccine Production Facility (CVPF)
Center for Advanced Cellular Therapeutics (CACT)
University of Pennsylvania Perelman School of Medicine
Contact Information9-112 South Tower, Big 421
3400 Civic Center Blvd
Philadelphia, PA, 19104
Office: (215) 662-3942
Email: siegeld@pennmedicine.upenn.edu
Specialty Division
Transfusion Medicine & Therapeutic Pathology, Cancer and Immunobiology
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.
Clinical Expertise
transfusion medicine, blood banking, apheresis, hematopoietic stem cell collection/processing, cGMP manufacture of cellular therapies for phase I first-in-human clinical trials
Itmat Expertise
Dr. Siegel's research focuses on the study of human auto and alloimmune repertoires in health and disease using repertoire cloning approaches (phage and yeast display technologies) for the production of monoclonal antibodies relevant to transfusion medicine, benign hematology, infectious diseases, and oncology. Current studies focus on developing targeted drug delivery methods using blood cell antibodies coupled to novel anti-thrombotic/anti-inflammatory molecules; cloning monoclonal non-human primate viral neutralizing antibodies for human in vivo antibody gene expression therapy; and isolating recombinant human, humanized, and canine antibody fragments for the design of T-cell chimeric antigen receptors and other therapies for cancer.
Education
Sc.B. (Biophysics), Brown University, 1977
Ph.D. (Biophysics), Harvard University, 1983
M.D. University of Pennsylvania, 1987
Specialty Certification
The American Board of Pathology, 1992
Postgraduate Training
Resident in Clinical Pathology, HUP, Philadelphia, PA, 1987-1989
Chief Resident, Division of Laboratory Medicine, HUP, Philadelphia, PA, 1989-1990
Fellowship, Transfusion Medicine, HUP, Philadelphia, PA, 1990-1991
Academic Medical Leadership Program, The Wharton School of the University of Pennsylvania, Philadelphia, PA, 2007-2008
Penn Medicine Leadership Forum, The Wharton School of the University of Pennsylvania, Philadelphia, PA, 2008-2009
Awards and Honors
Sigma Xi, 1977
NIH Pre-Doctoral Fellowship in the laboratory of Dr. Daniel Branton, Harvard University, Ph.D. dissertation: "Purification and characterization of human erythrocyte band 4.9, an actin bundling protein", 1977-1983
Honors in Biophysics, Brown University, undergraduate thesis: "Application of non-equilibrium thermodynamics to plasma membrane transport", 1977
Young Investigator Award, First Prize Recipient, Boston Blood Club, Harvard Medical School, 1983
Measey Foundation Scholar, University of Pennsylvania School of Medicine, 1983-1985
2 Young Investigator Awards, Academy of Clinical Laboratory Physicians and Scientists, 1988 Annual Meeting, 1988
Berwick Resident Teaching Award, Department of Pathology & Laboratory Medicine, University of Pennsylvania, 1990
Julius Erving Research Award of the Lupus Foundation of the Delaware Valley, 1991-1992
National Blood Foundation Research Award, 1991-1992
Clinical Investigator Award (K08), National Heart, Lung, and Blood Institute, NIH, 1991-1994
Basil O'Connor Scholar Research Award, March of Dimes Birth Defects Foundation, 1993-1995
National Blood Foundation Research Award, 1996-1997
National Blood Foundation Scholar, 1996
Peter C. Nowell Teaching Award, Department of Pathology & Laboratory Medicine, University of Pennsylvania, 1998
Leonard Berwick Memorial Teaching Award, University of Pennsylvania School of Medicine, 2000
Elected to John Morgan Society, 2001
Pennsylvania Biotechnology Greenhouse Award (translational research), 2003-2005
Christian R. and Mary F. Lindback Foundation Award for Distinguished Teaching, University of Pennsylvania, 2003
Philadelphia Antiques Show Proceeds Awardee, Board of Women’s Visitors, University of Pennsylvania Medical Center, 2003
Patient Health Care Hero, Penn Medicine, 2010
Elected to The Academy of Master Clinicians, Penn Medicine, 2013
Patient Health Care Hero, Penn Medicine, 2015
UPenn Health System Quality & Patient Safety Award, “Blood Delivery and Wastage in the PeriOperative Setting”, 2016
RISE (Research Innovation in Scientific Excellence) Award from AABB for best original research article published in Transfusion in 2016, 2017
Gift of Life Award, Lee Wynn Foundation, 2018
Francis S. Morrison, MD Memorial Lectureship, American Association for Apheresis, 2018
Robert de Villiers Spiral of Life Award, Leukemia & Lymphoma Society, 2020
Honorary Lecturer Award, American Association of Apheresis, 2020
SITC Team Science Award, Society for Immunotherapy of Cancer, 2020
Dale E. Smith Memorial Award, National Blood Foundation, American Association of Blood Banks, 2020
Patient Health Care Hero, Penn Medicine, 2020
Tibor Greenwalt Memorial Award and Lectureship, American Association of Blood Banks, 2021
“Startup of the Year” award for Founder of Vetigenics, LLC, Penn Center for Innovation, 2021
Hall of Fame, National Blood Foundation of the AABB, 2022
Press Ganey Pinnacle of Excellence Human Experience Award for Outpatient Practices, Apheresis Center, HUP, 2022
Press Ganey Pinnacle of Excellence Human Experience Award for Outpatient Practices, Apheresis Center, HUP, 2023
Memberships and Professional Organizations
American Association for Cell Biology, 1981 - 2008
American Society of Hematology, 1987 - present
AABB, 1989 - Present
Scientific Review Panel, Program Project on Prion Diseases, National Institute on Aging, 1998 - 1998
"Structural Analysis of Monoclonal Antibodies to Blood Group Antigens" for 4th International Workshop on Monoclonal Antibodies Against Human Red Blood Cells and Related Antigens, Paris, 1999 - 2001
Scientific Subcommittee on Hemoglobin/Red Cell, American Society of Hematology, 1999 - 2003
NIH/AABB-Sponsored Scientific Think Tank on "Setting the Research Agenda for Immunobiology in Transfusion Medicine", 1999 - 2000
Scientific Subsection Committee, American Association of Blood Banks, 1999 - present
Medical Advisory Committee, Penn-Jersey Division of the American Red Cross, 2000 - present
John Morgan Society, 2001 - present
American Society for Apheresis, 2001 - present
PhenoTech, Inc. (UPenn start-up), 2003 - 2009
Clinical Applications and Standards Committee, American Society for Apheresis, 2004 - present
Hema-Quebec, Quebec City, Canada, 2004 - 2005
FDA Workshop on Molecular Methods in Transfusion Medicine, 2006 - 2007
Hema-Quebec, Quebec City, Canada, 2006 - 2007
NIH Hematology Small Business Activities [SBIR/STTR] Special Emphasis Panel, 2006 - 2010
NIH NHLBI Strategic Planning Meeting "Research in Global Blood Safety and Availability, Domestic and International", 2006 - 2007
Executive Committee of the Medical Advisory Board, Penn-Jersey Division of the American Red Cross, 2008 - present
NIH Study Section "Selected Topics in Transfusion Medicine" (ZRG1 VH-E 50R), 2010 - Present
NIH, Member, Selected Topics in Transfusion Medicine Study Section, 2010 - Present
International Society for Cellular Therapy, 2017 - present
Department of Transfusion Medicine, National Institutes of Health, 2017 - Present
NIH NHLBI NITM NRSA Institution Research Training Grant (T32), 2019 - Present
NIH NHLBI NITM NRSA Institution Research Training Grant (T32), 2020 - 2026
Society for Immunotherapy of Cancer, 2021 - present
AABB, 2024 - Present
Web Links
Clinical/Research Fellowship in Transfusion Medicine
Division of Transfusion Medicine and Therapeutic Pathology
Selected Publications
Cytokine-mediated CAR T therapy resistance in AML
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., Nature Medicine in press(): , 2024
Red cell exchange for rapid leukoreduction in adults with hyperleukocytosis and leukostasis
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., Blood 143(): 1049-1054, 2024
Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: Phase 1 trial interim results
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., Nature Medicine 30(): 1320-1329, 2024
Tissue-resident memory CAR T cells with stem-like characteristics display enhanced efficacy against solid and liquid tumors
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., Cell Reports Medicine 4(): 101053, 2023
Mechanisms of inhibition of human monoclonal antibodies in immune thrombotic thrombocytopenic purpura
Halkidis, K., Meng, C., Liu, S., Mayne, L., Siegel, D.L., Zheng, X.L., Blood 141(): 2993-3005, 2023
Development and pharmacokinetic assessment of a fully canine anti-PD-1 monoclonal antibody for comparative translational research in dogs with spontaneous tumors
Yoshimoto, S., Chester, N., Xiong, A., Radaelli, E., Wang, H., Brillantes, M., Gulendran, G., Glassman, P., Siegel, D.L., Mason, N.J, mAbs 15(): e2004638-1 to e2004638-11, 2023
Anti-BCMA/CD19 CAR T Cells with early immunomodulatory maintenance for multiple myeloma responding to initial or later-line yherapy
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., Blood Cancer Discovery 4(): 118-133, 2023
Type I interferon signaling via the EGR2 transcriptional regulator potentiates CAR T cell-intrinsic dysfunction
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., Cancer Discovery 13(): 1636-1655, 2023
Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues
Feng, Z., He, X., Zhang, X., Wu, Y., Xing, B., Knowles, A., Shan, Q., Miller, S., Hojnacki, T., Ma, J., Katona, B.W., Gade, T.P.F., Siegel, D.L., Schrader, J., Metz, D.C., June, C.H., Hua X., Nature Cancer 3(): 581-594, 2022
Anti-CD19 CAR T cells in combination with Ibrutinib for the treatment of chronic lymphocytic leukemia
Gill, S., Vides, V., Frey, N.V., Hexner, E., Metzger, S., O'Brien, M., Hwang, W-T, Brogdon, J.L., Davis, M.M., Fraietta, J.A., Gaymon, A.L., Gladney, W.L., Lacey, S.F., Lamontagne, A., Mato, A.R., Maus, M.V., Melenhorst, J.J., Pequignot, E., Ruella, M., Shestov, M., Byrd, J.C., Schuster, S.J., Siegel, D.L., Levine, B.L., June, C.H., Porter, D.L., Blood Advances 6(): 5774-5785, 2022
