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
University of Pennsylvania Perelman School of Medicine

Contact Information510 Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 898-9655


Specialty Division

Transfusion Medicine & Therapeutic Pathology, Immunobiology and Experimental Pathology

Research Expertise

Research Interests

Production and characterization of pathogenic human monoclonal auto- and alloantibodies

Research Summary

My laboratory is interested in characterizing the human immune response to auto- and alloantigens on a molecular level in order to understand more about human immune repertoire development. Our goal is to use this information to develop specific therapeutic agents that down-regulate immune responses in the settings of autoimmune disease such as immune hemolytic anemias and thrombocytopenias, transfusion reactions, hemolytic disease of the newborn, and acute rejection of solid organ allografts.
To approach these problems experimentally, we have combined Fab/phage-display technology with a novel cell-surface panning method to isolate large arrays of clinically significant human monoclonal antibodies from individual patients. This approach has enabled us to study the genetic and immunological properties of pathogenic auto- and alloantibodies.

Clinical Expertise

transfusion medicine, blood banking, apheresis, hematopoietic stem cell collection/processing

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

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
National Blood Foundation Research Award, 1991-1992
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
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

Memberships and Professional Organizations

American Association for Cell Biology, 1981 - Present
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 - Present
NIH/AABB-Sponsored Scientific Think Tank on "Setting the Research Agenda for Immunobiology in Transfusion Medicine", 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
Scientific Subsection Committee, American Association of Blood Banks, 1999 - Present
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
Hema-Quebec, Quebec City, Canada, 2004 - Present
Clinical Applications and Standards Committee, American Society for Apheresis, 2004 - Present
FDA Workshop on Molecular Methods in Transfusion Medicine, 2006 - Present
NIH Hematology Small Business Activities [SBIR/STTR] Special Emphasis Panel, 2006 - Present
Hema-Quebec, Quebec City, Canada, 2006 - Present
NIH NHLBI Strategic Planning Meeting "Research in Global Blood Safety and Availability, Domestic and International", 2006 - Present
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
NIH, 2010 - Present

Web Links

Selected Publications

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

Immunotherapy of medullary thyroid carcinoma by GDNF family receptor alpha 4 (GFRalpha4)-targeted adoptive T cell immunotherapy

Bhoj V., Nunez-Cruz S., Feldman M.D., Mansfield K., Rader C., Siegel D.L., Milone M.C., American Association for Cancer Research 2016 Annual Meeting, New Orleans, LA., 2016

CAR-T cell therapies from the transfusion medicine perspective

Fesnak, A., Chie, Y.L., Siegel, D.L., Maus, M., Transfusion Medicine Reviews 30(): 139-145, 2016

A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

Fuentes, R.E., Zaytsev, S., Sook Ahn, H., Hayes, V., Kowalska, M.A., Lambert, M.P., Wang, Y., Siegel, D.L., Bougie, D.W., Aster, R.H., Myers, D.D., Stepanova, V., Cines, D.B., Muzykantov, V.R., Poncz, M., J Clin Invest 126(): 483-494, 2016

Mitochondrial DNA released following necroptosis accumulates on RBCs

Mei J., Qing D., Hotz M., Siegel D.L., Sondheimer N., Mangalmurti N.S., American Thoracic Society 2016 Conference, San Francisco, CA, 2016

Rh and LW Blood Groups

Siegel D.L., Westhoff, C, Rossi’s Principles of Transfusion Medicine, 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

Delivery of drugs bound to erythrocytes: new avenues for an old intravascular carrier

Villa CH., Pan DC., Zaitsev S., Cines D.B., Siegel D.L., Muzykantov, V.R., Therapeutic Delivery 6(): 795-826, 2015

Persistence of anti-desmoglein 3 IgG+ B-cell clones in pemphigus patients over years

Hammers, C.M., Chen, J., Lin, C., Kacir, S., Siegel, D.L., Payne, A.S., Stanley, J.R., J Invest Dermatol 135(): 742-749, 2015

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