BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Roland W. Herzog
Professor of Pediatrics
eRA COMMONS USER NAME (credential, e.g., agency login)
HERZOG
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
University of Kaiserslautern (Germany)
Auburn University, AL
The Children’s Hospital of Philadelphia
(BS)
PhD
postdoc
07/92
08/96
06/00
Biology
Microbiology
Gene Therapy
A. Personal Statement
The goals of my research program are to develop a gene therapy for hemophilia using AAV vectors, to develop
immune tolerance protocols for coagulation factors and other therapeutic proteins used in treatment of genetic
disease, and to understand the role of immune regulation in tolerance induction. We are engaged in
development of oral tolerance protocols for hemophilia, drug-based immune tolerance protocols, tolerogenic
cell therapies, and improved gene therapy protocols based on AAV gene transfer. My laboratory is
investigating the mechanism of tolerance induction by hepatic gene transfer, the role of regulatory T cells in
tolerance to therapeutic protein antigens, mechanisms of innate immunity to AAV vectors, and the mechanism
of oral tolerance induction using transgenic plant derived antigen. Some of our work on tolerance induction was
summarized in Nature: 515: S166-S167. We are collaborating with several laboratories at the University of
Florida and other institutions to accomplish these goals.
B. Positions and Honors
Positions and Employment
1996-2000
Postdoctoral fellow, The Children’s Hospital of Philadelphia, Philadelphia, PA
2000-2005
Assistant Professor, Dept. Pediatrics, University of Pennsylvania, Philadelphia, PA
2005-2011
Associate Professor, Dept. Pediatrics, University of Florida (UF), Gainesville, FL
2006-2011
Associate Professor, Dept. Molecular Genetics and Microbiology, UF, Gainesville, FL
2008
Tenure awarded, UF, Gainesville, FL
2011Professor of Pediatrics, Molecular Genetics and Microbiology, UF, Gainesville, FL
Other Experience and Professional Memberships
1994Member, American Association for the Advancement of Science
1996Member, American Society of Gene and Cell Therapy (ASGCT)
1996Member, American Society of Hematology
2002-04
Ad hoc member, NIH Small Business Grants study section
2001>50 invited lectures at local, national, and international level; Chair, multiple scientific sessions,
workshops, and symposia
2003Mentor of pre- and postdoctoral trainees on 4 NIH T32 and F32 training grants
2004-2009
Ad hoc member, NIH Hemostasis and Thrombosis study section
2006Member, Genetics Institute, Shands Cancer and Powell Gene Therapy Centers, UF
2006Member, editorial board, Current Gene Therapy
2006-09
Member, editorial board, Molecular Therapy
2006-08
Chair, ASGCT Immunology of Gene Therapy Committee
2007-10
Member, editorial board, Gene Therapy
2008-10
Co-Chair, ASGCT Education Committee
2009-10
Book editor, Gene Therapy Immunology and A Guide to Human Gene Therapy
2009Member, editorial board, Human Gene Therapy
2010-15
Deputy editor, Molecular Therapy
2010Executive editor, Journal of Genetic Syndromes & Gene Therapy (open access)
2010-11
Coordinating reviewer, gene therapy abstracts, American Society of Hematology (ASH)
2011
Ad hoc member, NIH Targeted Approaches Genetic Diseases (TAG) study section
2011
Editor, e-book, Frontiers in Microbial Immunology
2011-15
Member, NIH Hemostasis and Thrombosis study section
2012
Invited perspective article: Science 338: 748-749
2014-16
2015-18
Treasurer, ASGCT
Editor-in-Chief, Molecular Therapy Methods & Clinical Development
Honors
1989-94
19941997
1998
1998
2000-03
2003
2007-09
2009
2010
2010
2012
2013-14
Fellow, Konrad-Adenauer-Foundation, St. Augustin, Germany
Member, Honor Society of Phi Kappa Phi
Best presentation by postdoctoral investigator, Penn Vascular Biology retreat
Best trainee abstract award, Philadelphia Workshop on Thrombosis and Hemostasis
Presentation, Plenary Session, ASH annual meeting
Career Development Award, National Hemophilia Foundation
Outstanding New Investigator Award, ASGCT
Bayer Hemophilia Award
State-of-the-Art lecturer, International Society on Thrombosis and Haemostasis World Congress
Introducer, Plenary Session, ASH annual meeting
Outstanding service award, ASGCT
Faculty Research Award (Basic Science), University of Florida College of Medicine
Children’s Miracle Network Scholar
C. Selected Peer-reviewed Publications (selected from >130 publications and 2 books):
1. Herzog RW, Hagstrom JN, Kung SH, Tai SJ, Wilson JM, Fisher KJ, High KA (1997) Stable gene transfer
and expression of human factor IX after intramuscular injection of adeno-associated virus vector. Proc Natl
Acad Sci USA 94: 5804-5809 (PMCID: PMC20861)
2. Herzog RW, Yang EY, Hagstrom JN, Couto LB, Elwell D, Fields PA, Burton M, Bellinger DA, Read MS,
Brinkhous KM, Podsakoff GM, Nichols TC, Kurtzman GJ, High KA (1999) Long-term phenotypic correction
of canine hemophilia B by AAV-mediated gene transfer of blood coagulation factor IX. Nat Med 5: 56-63
[Commentary: Nat Med 5: 21-22] (PMID: 9883840)
3. Mingozzi F, Liu YL, Dobrzynski E, Kaufhold A, Liu JH, Wang YQ, Arruda VR, High KA and Herzog RW
(2003) Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer. J.
Clin. Invest. 111: 1347-1356 (PMCID: PMC154443)
4. Dobrzynski E, Mingozzi F, Liu YL, Bendo E, Cao O, Wang L, Herzog RW (2004) Induction of antigenspecific CD4+ T cell anergy and deletion by in vivo viral gene transfer. Blood 104: 969-977 [Commentary:
Blood 104: 910-911] (PMID: 15105293)
5. Dobrzynski E, Fitzgerald JC, Cao O, Mingozzi F, Wang L, Herzog RW (2006) Prevention of cytotoxic T
lymphocyte responses to factor IX expressing hepatocytes by gene transfer-induced regulatory T cells.
Proc Natl Acad Sci USA, 103: 4592-4597 (PMID: 16537361)
6. Cao O, Dobrzynski E, Wang L, Nayak S, Mingle B, Terhorst C, Herzog RW (2007) Induction and role of
regulatory CD4+CD25+ T cells in tolerance to the transgene product following hepatic in vivo gene transfer.
Blood 110: 1132-1140 [Commentary: Blood 110: 1089] (PMCID: PMC1939896)
7. Verma D, Moghimi B, LoDuca PA, Singh HD, Hoffman BE, Herzog RW¶, Daniell H¶ (2010) Oral
administration of bioencapsulated factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia
B mice. Proc Natl Acad Sci USA 107: 7101-7106 [Commentary: Proc Natl Acad Sci USA 107: 6553] (¶
corresponding authors) (PMCID: PMC2872434)
8. Martino AT, Suzuki M, Markusic DM, Zolotukhin I, Ryals RC, Moghimi B, Ertl HCJ, Muruve DA, Lee B,
Herzog RW (2011) The genome of self-complementary AAV vectors increases TLR9-dependent innate
immune responses in the liver. Blood 117: 6459-6468 (PMCID: PMC3123017)
9. Moghimi B, Sack BK, Nayak S, Markusic DM, Mah CS, Herzog RW (2011) Tolerance induction to factor
VIII by transient co-administration with rapamycin. J. Thromb. Haemost. 9: 1524-1533 [Commentary: J.
Thromb. Haemost. 9: 1521-1523] (PMCID: PMC3154987)
10. Martino AT, Basner-Tschakarjan A, Markusic DM, Finn JD, Hinderer C, Zhou S, Ostrov DA, Srivastava A,
Ertl HCJ, Terhorst C, High KA, Mingozzi F, Herzog RW (2013) Engineering AAV vectors to minimize
targeting of transduced hepatocytes by capsid-specific CD8+ T cells. Blood 121: 2224-2233 [Commentary:
Blood 121: 2168-2169] (PMCID: PMC3606062)
11. Markusic DW, Hoffman BE, Perrin GQ, Nayak S, Wang X, LoDuca PA, High KA, Herzog RW (2013)
Effective gene therapy for hemophilic mice with pathogenic factor IX antibodies. EMBO Mol. Med. 5: 16981709 (PMCID: PMC3840486)
12. Wang X, Moghimi B, Zolotukhin I, Morel L, Cao O, Herzog RW (2014) Immune tolerance induction to factor
IX through B cell gene transfer – TLR9 signaling delineates between tolerogenic and immunogenic B cells.
Mol Ther 22: 1139-1150 (PMCID: PMC4048896)
13. Sherman A, Su J, Lin S, Wang X, Herzog RW¶, Daniell H¶ (2014) Suppression of inhibitor formation
against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells.
Blood 124: 1659-1668 (¶ corresponding authors) [cover article; commentaries: Blood 124: 1548-1549;
Science 345: 1576] (PMCID: PMC4155273)
14. Wang X, Su J, Sherman A, Rogers GL, Liao G, Hoffman BE, Leong KW, Terhorst C, Daniell H, Herzog RW
(2015) Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response
including LAP+CD4+ T cells. Blood. Epub ahead of print Feb 19, 2015
15. Biswas M, Sarkar D, Kumar SRP, Nayak S, Rogers GL, Markusic DM, Liao G, Terhorst C, Herzog RW
(2015) Synergy between rapamycin and FLT3 ligand enhances plasmacytoid dendritic cell-dependent
induction of CD4+CD25+FoxP3+ Treg. Blood, in press
D. Research Support
Ongoing Research Support
2 P01 HL078810 (Ertl)
1/07/2005-06/30/2015
NIH/NHLBI (WISTAR Institute)
Immune Responses to AAV-Mediated F.IX Gene Transfer: Project 3: Pathways towards immune tolerance to
coagulation factors (Herzog)
The aims of this proposal are to develop novel protocols for generation and expansion of factor IX-specific
Treg in vivo and in vitro, to test for suppression of immune responses to F.IX by generated Treg in hemophilia
B mice, and to better define immune regulatory pathways that promote tolerance to F.IX.
Role: Project Leader
R01 HL097088 (MPI: Srivastava, Herzog, Zolotukhin)
07/01/10-03/31/2015
NIH/NHLBI
Next Generation of Recombinant AAV Serotype Vectors for Gene Therapy
This proposal seeks to define the mechanism by which tyrosine mutant AAV capsids direct higher efficiency of
gene transfer and potentially circumvent T cell responses against AAV capsid, to develop a baculovirus-based
production system for such novel AAV vectors, and to test efficacy in treatment of murine and canine
hemophilia B. The grant is a collaborative effort of 3 PIs (Herzog, Srivastava, Zolotukhin) within the Div.
Cellular and Molecular Therapy at UF.
Role: PI
2 R01 AI51390 (Herzog)
04/01/02-11/30/17
NIH/NIAAD
Immunology of factor IX gene transfer to liver
The objectives of this grant are to develop superior protocols for immune tolerance to factor IX by hepatic gene
transfer with alternate AAV serotypes, to study the mechanism of tolerogenic antigen presentation in the liver
using ovalbumin gene transfer, and to induce factor IX-specific regulatory T cells prior to gene transfer using a
F.IX peptide, rapamycin, and IL-10.
Role: PI
R01 HL109442 (Bioengineering Research Partnership, MPI: Herzog, Daniell, Leong)
8/01/2011-6/30/2016
NIH/NHLBI
Oral therapy for hemophilia A
This proposal seeks to develop oral tolerance and oral gene therapy protocols for hemophilia A using
transgenic edible crop plants (lettuce) and nanoparticle vector technologies. The project is collaborative
between the University of Florida, University of Central Florida, and Duke University
Role: Contact-PI
R01 HL107904 (MPI: Daniell, Herzog)
7/15/2011-5/31/2015
NIH/NHLBI
Oral immune modulatory therapy using antigens bioencapsulated in plant cells
This proposal seeks to develop oral tolerance for hemophilia B using transgenic edible crop plants. The
mechanism of tolerance induction will be studied in hemophilia B mice, and the approach will be tested in a
large animal model (hemophilia B dogs).
Role: PI
R01 HL073838 (PI: A. Davidoff)
7/01/2013-6/30/2016
NIH-NHLBI (St Jude Children’s Research Hospital)
rAAV-Mediated Gene Therapy for Hemophilia A
The major goals of the proposal are to generate and test a better expression cassette for factor VIII, to use
hepatic AAV gene transfer to reverse an existing antibody response to FVIII in rhesus macaques, and to
increase FVIII expression using drugs that affect chomatin structure. The Herzog lab will analyze rhesus
macaques samples for antibody formation against F.VIII for F.VIII-specific lymphocyte responses, in order to
define a mechanism for tolerance induction.
Role: Co-investigator
Pfizer Hemophilia Award (Brusko)
9/01/2013-8/30/2015
ASPIRE program
Regulatory T cells with chimeric antigen receptor for immunetolerance to factor VIII
This grant aims to generated factor VIII-specific Treg by ex vivo gene transfer of a chimeric antigen receptor
(CAR).
Role: Co-investigator
Sponsored Research Agreement, (Daniell, Herzog)
05/01/2014-04/30/2018
Novo Nordisk
Oral tolerance to factor VIII
This investigation will produce large quantities of chloroplast transgenic plants expressing factor VIII antigen
toward translational studies (non-human primates). Large-scale production of freeze-dried material will be
optimized, and a wide range of plant material doses (tobacco and lettuce) and dosing regimens will initially be
tested for prevention and reversal of inhibitors in factor VIII replacement therapy in two different strains of
hemophilic mice.
Role: PI
Completed Research Support (past 3 years):
Bayer Hemophilia Program (Daniell)
7/01/2010-6/30/2013
Prevention of inhibitors by oral delivery of coagulation factors
The proposed work is to engineer chloroplast transgenic tobacco plants for initial testing of the hypothesis that
plant-derived factor VIII can induce oral tolerance in hemophilia A mice.
Role: Co-investigator
Bayer Hemophilia Program (Srivastava)
7/01/2010-6/30/2012
Special Project Award
Novel AAV vectors and strategies for the potential gene therapy of hemophilia A
This proposal is to generate novel AAV vectors for factor VIII expression followed by testing in hemophilia A
mice and dogs.
Role: Co-investigator
1 R01 AI78967 (Cao)
09/01/08-08/31/12
NIH/NIAID
Tailoring AAV vectors for glioma immunotherapy
This investigation seeks to generate AAV vectors with tropism for glioma cells and for generation of immunity
against glioma in vivo. The grant also includes experiments attempting to suppress Treg responses in order to
enhance immunity against the tumor cells.
Role: Co-investigator