PEOPLE

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

Email: siegeld@pennmedicine.upenn.edu

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.

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
Measey Foundation Scholar, University of Pennsylvania School of Medicine, 1983-1985
Young Investigator Award, First Prize Recipient, Boston Blood Club, Harvard Medical School, 1983
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
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

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
NIH/AABB-Sponsored Scientific Think Tank on "Setting the Research Agenda for Immunobiology in Transfusion Medicine", 1999 - 2000
Scientific Subcommittee on Hemoglobin/Red Cell, American Society of Hematology, 1999 - 2003
"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
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 - 2005
Clinical Applications and Standards Committee, American Society for Apheresis, 2004 - present
NIH NHLBI Strategic Planning Meeting "Research in Global Blood Safety and Availability, Domestic and International", 2006 - 2007
NIH Hematology Small Business Activities [SBIR/STTR] Special Emphasis Panel, 2006 - 2010
FDA Workshop on Molecular Methods in Transfusion Medicine, 2006 - 2007
Hema-Quebec, Quebec City, Canada, 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
International Society for Cellular Therapy, 2017 - present
Board of Scientific Counselors, Department of Transfusion Medicine, National Institutions of Health, 2017 - 2017

Web Links


Selected Publications

Delayed Viral rebound during ATI after infusion of CCR5 ZFN-treated CD4 T cells.

Tebas, P., Jadlowsky, J., Shaw, P., Lee, G., Ando, D., Kim, S., Naing, S.Y., Lacey, S., Levine, B.L., Siegel, D.L., June, C.H., Riley, J.L., 2019 Conference on Retroviruses and Opportunistic Infections (CROI), 2019

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

Prospective clinical trial of anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia shows a high response rate

Gill, S.I., Vides, V., Frey, N.V., Metzger, S., O'Brien, M., Hexner, E., Mato, A.R., Lacey, S.F., Melenhorst, J.J., Pequignot, E., Gladney, W.L., Hwang, W-T, Lamontagne, A., Davis, M., Byrd, J.C., Schuster, S.J., Siegel, D.L., Isaacs, R.E., June, C.H., Porter, D.L., Blood 132(): 298, 2018

Cloning and analysis of bullous pemphigoid anti-BP180 IgG and IgE autoantibodies indicates predominance of VL1-47 gene usage and direct (from IgM) and indirect (through IgG) class switching to IgE

Hammers, C.M., Yuan, H., Lin, C., Tang, H.Y., Siegel, D.L., Stanley, J.R., Exp Dermatol 27(): E64-E65, 2018

Clinical predictors of T cell fitness for CAR T cell manufacturing and efficacy in multiple myeloma

Dancy, E., Garfall, A.L., Cohen, A.D., Fraietta, J.A., Davis, M., Levine, B.L., Siegel, D.L., Stadtmauer, E.A., Vogl, D.T., Waxman, A., Rapoport, A.P., Milone, M.D., June, C.H., Melenhorst, J.J., Blood 132(): 1886, 2018

CD19-directed CAR T-cell (CTL019) product viability and clinical outcomes in non-Hodgkin lymphomas and B-cell acute lymphoblastic leukemia

Chong, E.A., Levine, B.L., Grupp, S.A., Davis, M., Siegel, D.L., Maude, S.L., Gladney, W.L., Frey, N.V., Porter, D.L., June, C.H., Schuster, S.J., Blood 132(): 197, 2018

Vector integration and efficacy of CD19-directed CAR T cell therapy in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL).

Nobles, C.L., Everett, J.K., Reddy, S., Fraietta, J.A., Porter, D.L., Frey, N.V., Grupp, S.A., Siegel, D.L., Lacey, S.F., June, C.H., Bushman, F.D., Melenhorst, J.J., Blood 132(): 4548, 2018

Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma

Garfall, A., Stadtmauer, E., Hwang, W.-T., Lacey, S., Melenhorst, J., Krevvata, M., Carroll, M., Matsui, W., Wang, Q., Dhodapkar, M., Dhodapkar,K., Das, R., Vogl, D., Weiss, B., Cohen, A., Mangan, P., Ayers, E., Nunez-Cruz , S., Kulikovskaya, I., Davis, M., Lamontagne, A., Dengel, K., Kerr, N., Young, R., Siegel, D.L., Levine, B., Milone, M.C., Maus, M., June, C.H., JCI Insight 3(): e120505, 2018

Ohayon, Y., Corl, C.M., Leskowitz, R.M., Malykhin, A., Arostegui, S.M., Hennesy, N.A, Ngo, S., Levine, B.L., Siegel, D.L., Fesnak, A., Davis, M.M.

Robust automated cell counter and viability measurement for engineered T cell product release,, Cytotherapy 20(): S69, 2018

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, Nature Medicine 24(): 563-571, 2018

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