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, 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


Specialty Division

Transfusion Medicine & Therapeutic Pathology, Immunobiology and Experimental Pathology

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 the molecular genetics of human auto- and alloantibodies responsible for blood cell-related disorders such as immune cytopenias (ITP, AIHA, TTP), hemolytic transfusion reactions, and hemolytic disease of the newborn. The Siegel laboratory has developed several phage display-related technologies for the cloning of human immune repertoires and the production of human monoclonal antibodies. These studies have led to the development of novel diagnostic reagents and antibodies with therapeutic potential.


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

Honors in Biophysics, Brown University, undergraduate thesis: "Application of non-equilibrium thermodynamics to plasma membrane transport", 1977
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
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
Clinical Investigator Award (K08), National Heart, Lung, and Blood Institute, NIH, 1991-1994
Julius Erving Research Award of the Lupus Foundation of the Delaware Valley, 1991-1992
National Blood Foundation Research Award, 1991-1992
Basil O'Connor Scholar Research Award, March of Dimes Birth Defects Foundation, 1993-1995
National Blood Foundation Scholar, 1996
National Blood Foundation Research Award, 1996-1997
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
Philadelphia Antiques Show Proceeds Awardee, Board of Women’s Visitors, University of Pennsylvania Medical Center, 2003
Christian R. and Mary F. Lindback Foundation Award for Distinguished Teaching, University of Pennsylvania, 2003
Pennsylvania Biotechnology Greenhouse Award (translational research), 2003-2005
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
Francis S. Morrison, MD Memorial Lectureship, American Association for Apheresis, 2018

Memberships and Professional Organizations

American Association for Cell Biology, 1981 - 2008
American Society of Hematology, 1987 - present
American Association of Blood Banks, 1989 - present
Scientific Review Panel, Program Project on Prion Diseases, National Institute on Aging, 1998 - 1998
Scientific Subsection Committee, American Association of Blood Banks, 1999 - present
"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
Medical Advisory Committee, Penn-Jersey Division of the American Red Cross, 2000 - present
American Society for Apheresis, 2001 - present
John Morgan Society, 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
Hema-Quebec, Quebec City, Canada, 2006 - 2007
FDA Workshop on Molecular Methods in Transfusion Medicine, 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, Member, Selected Topics in Transfusion Medicine Study Section, 2010 - Present
NIH Study Section "Selected Topics in Transfusion Medicine" (ZRG1 VH-E 50R), 2010 - Present
Board of Scientific Counselors, Department of Transfusion Medicine, National Institutions of Health, 2017 - 2017
International Society for Cellular Therapy, 2017 - present

Web Links

Selected Publications

Biocompatible coupling of therapeutic fusion proteins to human erythrocytes

Villa, C.H., Pan, D.C., Johnston, I., Greineder, C.F., Walsh, L., Hood, E., Cines, D.B., Poncz, M., Siegel, D.L., Muzykantov, V.R., Blood Advances 2(): 165-176, 2018

Red blood cell targeting of liposomes provides markedly enhanced circulation

Villa, C.H., Marcos-Contreras, O.A., Greineder, C.F., Hood, E., Shuvaeva, T., Walsh, L., Meyerson, J., Glassman, P., Brenner, J.S., Siegel, D.L., Muzykantov, V.R., Center for Targeted Therapeutics and Translation Nanomedicine Annual Symposium, 2017

Erythrocytes as carriers for drug delivery in blood transfusion and beyond

Villa C.H., Cines D.B., Siegel D.L., Muzykantov V.R., Transfusion Medicine Reviews 31(): 26-35, 2017

Identification of functional determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia

Fraietta J.A., Lacey S.F., Orlando E.J., Pruteanu-Malinici I., Gohil M., Lundh S., Boesteanu A.C., Wang Y., O’Connor R.S., Hwang W.-T., Pequignot E., Ambrose D.E., Zhang C., Wilcox N., Bedoya F., Dorfmeir C., Chen F., Tian L., Parakandi H., Gupta M., Young R.M., Johnson F.B., Kulikovskaya I., Liu L., Xu J., Kassim S.H., Suhoski-Davis M.M., Levine B.L., Frey N.V., Siegel D.L., Huang A.C., Wherry E.J., Bitter H., Brogdon J.L., Porter D.L., June C.H., Melenhorst J.J., Blood 130(): 3181, 2017

Targeting thrombomodulin to circulating red blood cells augments its protective effects in models of endotoxemia and ischemia-reperfusion injury

Carnemolla, R., Villa, C.H., Greineder, C.F., Zaitsev, S., Kowalska, A., Atochin, D.N., Cines, D.B., Siegel, D.L., Esmon, C.T. Muzykantov, V.R., FASEB J 31(): 761-770, 2017

Immune plasma for the treatment of severe influenza: an open-label, multicenter, phase 2 randomised study

Beigel, J.H., Tebas, P., Elie-Turenne, Marie-Carmelle, et al, The Lancet Respiratory Medicine 5(): 500-511, 2017

Proteomic analysis of pemphigus autoantibodies indicates a much larger, more diverse, and dynamic repertoire than determined by B-cell genetics

Chen, J., Zheng, Q., Hammers, C.M., Ellebrecht, C., Mukherjee, C., Tang, H-Y., Lin, C., Yuan, H-J., Pan, M., Langenhan, J., Komorowski, L., Siegel, D.L., Payne, A.S., Stanley, J.R., Cell Reports 18(): 237-247, 2017

ADAMTS13 Autoantibodies Cloned from Patients with Acquired Thrombotic Thrombocytopenic Purpura: 2. Pathogenicity in an animal model

Ostertag, E.M., Bdeir, K., Kacir, S., Thiboutot, M., Gulendran, G., Yunk, L., Hayes, V.M., Motto, D.G., Poncz, M., Zheng, X.L., Cines, D.B., Siegel, D.L., Transfusion 56(): 1775-1785, 2016

Phage antibody display libraries: a powerful antibody discovery platform for immunotherapy

Zhao A., Tohidkia M.R., Siegel D.L., Coukos G., Omidi Y., Critical Reviews in Biotechnology 36(): 276-289, 2016

ADAMTS13 Autoantibodies Cloned from Patients with Acquired Thrombotic Thrombocytopenic Purpura: 1. Structural and functional characterization in vitro

Ostertag, E.M., Kacir, S., Thiboutot, M., Gulendran, G., Zheng, X.L., Cines, D.B., Siegel, D.L., Transfusion 56(): 1763-1774, 2016

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