Download BIOGRAPHICAL SKETCH Roland W. Herzog HERZOG

BIOGRAPHICAL SKETCH
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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 protein 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, and improved
gene therapy protocols based on hepatic 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, the interactions between innate immunity and immune regulatory cells, and the mechanism of oral
tolerance induction using transgenic plant derived antigen. 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 3 NIH T32 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
2007
Associate editor, special issue, Current Gene Therapy
2008-10
Co-Chair, ASGCT Education Committee
2009
Editor, Gene Therapy Immunology book
2009Member, editorial board, Human Gene Therapy
2009-12
Mentor of postdoctoral trainee with NIH Ruth Kirschstein national merit scholarship
2010
Co-editor, A Guide to Human Gene Therapy textbook
2010Deputy Editor, Molecular Therapy
2010Member, ASGCT Nominating Committee
2010Executive editor, Journal of Genetic Syndromes & Gene Therapy (open access)
2010-11
2011
2011
2011
2011-
Coordinating reviewer, gene therapy abstracts, American Society of Hematology (ASH)
Ad hoc member, NIH Targeted Approaches Genetic Diseases (TAG) study section
Guest editor, special topic, Frontiers in Microbial Immunology
Guest editor, special topic, Journal of Genetic Syndromes & Gene Therapy
Member, NIH Hemostasis and Thrombosis study section
Honors
1989-94
19941997
1998
1998
2000-03
2003
2007-09
2009
2010
2010
2012
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
C. Selected Peer-reviewed Publications (selected from 55 research articles, 42 reviews and commentaries,
3 methods articles, 2 books, and 109 abstracts):
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
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]
3. Herzog RW, Mount JD, Tillson DM, Goodman SA, Robinson N, McClelland ML, Bellinger D, Nichols TC,
Arruda VR., Lothrop CD Jr., and High KA (2002). Sustained phenotypic correction of hemophilia B dogs
with a factor IX null mutation by liver-directed gene therapy. Blood 99: 2670-2676 [plenary paper;
commentary: Blood 99:2635-2636]
4. 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
5. 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]
6. Wang L, Dobrzynski E, Cao O, Herzog RW (2005) Systemic protein delivery by muscle-directed gene
transfer is limited by a local immune response. Blood 105: 4226-4234
7. 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
8. 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]
9. Nayak S, Cao O, Hoffman BE, Cooper M, Zhou S, Atkinson MA, Herzog RW (2009) Prophylactic immune
tolerance induced by changing the ratio of antigen-specific effector to regulatory T cells. J. Thromb.
Haemost. 7: 1523-1532
10. Cao O, Hoffman BE, Moghimi B, Nayak S, Cooper M, Zhou S, Ertl HCJ, High KA, Herzog RW (2009)
Impact of the underlying mutation and the route of vector administration on immune responses to factor IX
in gene therapy for hemophilia B. Mol Ther 17: 1733-1742
11. 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)
12. Jayandharan GR, Aslanidi GV, Martino AT, Jahn SC, Perrin GQ, Herzog RW, Srivastava A (2011)
Activation of the NF-κB pathway by AAV vectors and its implications in immune response and gene
therapy. Proc Natl Acad Sci USA 108: 3743-3748
13. Hoffman BE, Martino AT, Sack BK, Cao O, Liao G, Terhorst C, Herzog RW (2011) Non-redundant roles of
IL-10 and TGF-β in suppression of immune responses to hepatic AAV-factor IX gene transfer. Mol Ther 19:
1263-1272
14. 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
15. 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]
D. Research Support
Ongoing Research Support
2 PO1 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)
07/01/10-06/30/2014
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)
04/01/02-11/31/12
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 HL106687 (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
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
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
Bayer Hemophilia Program (Daniell)
7/01/2010-6/30/2012
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
R01 HL073838 (PI: A. Davidoff)
4/01/2011-3/31/2016
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/PI on Consortium Award to begin 4/1/2013
Completed Research Support (past 3 years):
Bayer Hemophilia Awards Program (Herzog)
07/01/07-06/30/09
Special Project Award
A novel protocol for tolerance induction to coagulation factors
This proposal seeks to develop a new protocol for induction of immune tolerance to coagulation factors in
treatment of hemophilia. The main focus of the grant is tolerance induction to factor VIII by targeting B and T
cells with monoclonal antibodies and drugs and by an oral tolerance protocol.
Role: PI
R21 HL089813-01(Herzog)
07/01/07-06/30/09
NIH-NHLBI
Bioencapsulated Factor IX for Oral Tolerance in Hemophilia B
The goals of this grant are to develop transgenic plants for oral tolerance induction to coagulation factor IX and
to test this approach in hemophilia B mice.
Role: PI