Brad E Hoffman

Brad E Hoffman, PhD

Associate Professor

Department: MD-PEDS-CELL / MOLEC THERP DIV
Business Phone: (352) 273-8152
Business Email: bhoffman@ufl.edu

About Brad E Hoffman

Associate Professor,

Department of Pediatrics

Department of Neuroscience

Lab Website http://hoffman.pediatrics.med.ufl.edu/

Accomplishments

Research Scientist Award
2018 · National multiple sclerosis society
Ambassador
2017-current · NIH-LRP Program
Recipient, Travel Grant
2016 · American Association of Immunologists
Recipient, Travel Grant
2016 · International Congress of Immunology
Mentor S.T.E.M Supernova
2015-current · Boy Scouts of America
Award in Hemophilia Research (ASPIRE)
2011 · Pfizer Pharmaceuticals
Immunology Grant Recipient
2011 · BD Bioscience
Kokomoor Award for Excellence in Pediatric Research
2010 · University of Florida, Department of Pediatrics
Research Fellowship
2007 · American Heart Association

Research Profile

The major focus of my research program is aimed at understanding and exploiting the unique molecular and cellular mechanisms required for the induction of immunological tolerance. As such, my research group is developing novel immunotherapies using the Adeno-associated virus (AAV) gene-therapy platform that are capable of inducing tolerogenic antigen-specific regulatory T cells (Tregs) as a therapeutic intervention for autoimmune and genetic disease such as Multiple Sclerosis. Recently, we were the first to demonstrate that an AAV vector could be used therapeutically to not only prevent development of disease, but to also abrogate preexisting (reverse) disease in multiple mouse models of Multiple Sclerosis.

Open Researcher and Contributor ID (ORCID)

0000-0002-5560-9580

Areas of Interest
  • Adeno-Associated Viral Gene Therapy
  • Autoimmune Disease
  • Gene therapy
  • Immune Tolerance
  • Immunotherapy
  • Multiple Sclerosis

Publications

2020
AAV3-miRNA vectors for growth suppression of human hepatocellular carcinoma cells in vitro and human liver tumors in a murine xenograft model in vivo.
Gene therapy. [DOI] 10.1038/s41434-020-0140-1. [PMID] 32152434.
2020
Type I IFN Sensing by cDCs and CD4+ T Cell Help Are Both Requisite for Cross-Priming of AAV Capsid-Specific CD8+ T Cells.
Molecular therapy : the journal of the American Society of Gene Therapy. 28(3):758-770 [DOI] 10.1016/j.ymthe.2019.11.011. [PMID] 31780366.
2020
Enhanced Transduction of Human Hematopoietic Stem Cells by AAV6 Vectors: Implications in Gene Therapy and Genome Editing.
Molecular therapy. Nucleic acids. 20:451-458 [DOI] 10.1016/j.omtn.2020.03.009. [PMID] 32276210.
2019
Regulatory T cells and TLR9 activation shape antibody formation to a secreted transgene product in AAV muscle gene transfer.
Cellular immunology. 342 [DOI] 10.1016/j.cellimm.2017.07.012. [PMID] 28888664.
2019
Liver induced transgene tolerance with AAV vectors.
Cellular immunology. 342 [DOI] 10.1016/j.cellimm.2017.12.002. [PMID] 29576315.
2018
Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis.
Molecular therapy : the journal of the American Society of Gene Therapy. 26(1):173-183 [DOI] 10.1016/j.ymthe.2017.09.001. [PMID] 28943274.
2017
Alpha-1 Antitrypsin-Deficient Macrophages Have Increased Matriptase-Mediated Proteolytic Activity.
American journal of respiratory cell and molecular biology. 57(2):238-247 [DOI] 10.1165/rcmb.2016-0366OC. [PMID] 28362108.
2017
Plasmacytoid and conventional dendritic cells cooperate in crosspriming AAV capsid-specific CD8+ T cells.
Blood. 129(24):3184-3195 [DOI] 10.1182/blood-2016-11-751040. [PMID] 28468798.
2017
The Balance between CD8+ T Cell-Mediated Clearance of AAV-Encoded Antigen in the Liver and Tolerance Is Dependent on the Vector Dose.
Molecular therapy : the journal of the American Society of Gene Therapy. 25(4):880-891 [DOI] 10.1016/j.ymthe.2017.02.014. [PMID] 28284982.
2016
Potential for cellular stress response to hepatic factor VIII expression from AAV vector.
Molecular therapy. Methods & clinical development. 3 [PMID] 27738644.
View on: PubMed
2016
Superior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid.
Molecular therapy : the journal of the American Society of Gene Therapy. 24(6):1042-1049 [DOI] 10.1038/mt.2016.61. [PMID] 27019999.
2016
Low cost delivery of proteins bioencapsulated in plant cells to human non-immune or immune modulatory cells.
Biomaterials. 80:68-79 [DOI] 10.1016/j.biomaterials.2015.11.051. [PMID] 26706477.
2015
Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.
Blood. 125(15):2418-27 [DOI] 10.1182/blood-2014-08-597070. [PMID] 25700434.
2015
Reprogramming Immune Response With Capsid-Optimized AAV6 Vectors for Immunotherapy of Cancer.
Journal of immunotherapy (Hagerstown, Md. : 1997). 38(7):292-8 [DOI] 10.1097/CJI.0000000000000093. [PMID] 26261893.
2014
Ex Vivo Expanded Autologous Polyclonal Regulatory T Cells Suppress Inhibitor Formation in Hemophilia.
Molecular therapy. Methods & clinical development. 1 [PMID] 25364772.
View on: PubMed
2013
Covert warfare against the immune system: decoy capsids, stealth genomes, and suppressors.
Molecular therapy : the journal of the American Society of Gene Therapy. 21(9):1648-50 [DOI] 10.1038/mt.2013.176. [PMID] 24008618.
2013
Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies.
EMBO molecular medicine. 5(11):1698-709 [DOI] 10.1002/emmm.201302859. [PMID] 24106230.
2012
Capsid Modified Aav2 Vectors Are Capable of Generating Vaccine-Mediated Protection
Molecular Therapy. 20:S257-S258
2012
Gene therapy research at the frontiers of viral immunology.
Frontiers in microbiology. 3 [DOI] 10.3389/fmicb.2012.00182. [PMID] 22783235.
2012
Optimization of Raav for Anti-Glioma Therapy
Molecular Therapy. 20:S226-S227
2012
Optimal Immunofluorescent Staining for Human Factor IX and Infiltrating T Cells following Gene Therapy for Hemophilia B.
Journal of genetic syndromes & gene therapy. S1 [PMID] 23264888.
View on: PubMed
2011
Nonredundant roles of IL-10 and TGF-β in suppression of immune responses to hepatic AAV-factor IX gene transfer.
Molecular therapy : the journal of the American Society of Gene Therapy. 19(7):1263-72 [DOI] 10.1038/mt.2011.33. [PMID] 21386826.
2011
Prevention and Reversal of Antibody Responses Against Factor IX in Gene Therapy for Hemophilia B.
Frontiers in microbiology. 2 [DOI] 10.3389/fmicb.2011.00244. [PMID] 22279442.
2010
High-efficiency transduction and correction of murine hemophilia B using AAV2 vectors devoid of multiple surface-exposed tyrosines.
Molecular therapy : the journal of the American Society of Gene Therapy. 18(12):2048-56 [DOI] 10.1038/mt.2010.172. [PMID] 20736929.
2010
Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice.
Proceedings of the National Academy of Sciences of the United States of America. 107(15):7101-6 [DOI] 10.1073/pnas.0912181107. [PMID] 20351275.
2009
Tolerance induction to cytoplasmic beta-galactosidase by hepatic AAV gene transfer: implications for antigen presentation and immunotoxicity.
PloS one. 4(8) [DOI] 10.1371/journal.pone.0006376. [PMID] 19652717.
2009
Systemic Expression of Transgene Product Is Not Required for Induction of Immune Tolerance By Aav2 Hepatic Gene Transfer
Molecular Therapy. 17
2009
Prophylactic immune tolerance induced by changing the ratio of antigen-specific effector to regulatory T cells.
Journal of thrombosis and haemostasis : JTH. 7(9):1523-32 [DOI] 10.1111/j.1538-7836.2009.03548.x. [PMID] 19583824.
2009
Impact of the underlying mutation and the route of vector administration on immune responses to factor IX in gene therapy for hemophilia B.
Molecular therapy : the journal of the American Society of Gene Therapy. 17(10):1733-42 [DOI] 10.1038/mt.2009.159. [PMID] 19603001.
2009
Hepatic gene transfer as a means of tolerance induction to transgene products.
Current gene therapy. 9(2):104-14 [PMID] 19355868.
View on: PubMed
2009
Improved induction of immune tolerance to factor IX by hepatic AAV-8 gene transfer.
Human gene therapy. 20(7):767-76 [DOI] 10.1089/hum.2008.161. [PMID] 19309290.
2008
A Prophylactic Protocol for the Prevention of Inhibitor Formation in Gene Therapy for Hemophilia B By Shifting the Balance From An Effector To a Regulatory T Cell Response
Blood. 112
2008
Coaxing the liver into preventing autoimmune disease in the brain.
The Journal of clinical investigation. 118(10):3271-3 [DOI] 10.1172/JCI37079. [PMID] 18802483.
2007
Muscle as a target for supplementary factor IX gene transfer.
Human gene therapy. 18(7):603-13 [PMID] 17594244.
View on: PubMed
2003
Apoptosis of infiltrating T cells in the central nervous system of mice infected with Theiler’s murine encephalomyelitis virus.
Virology. 315(1):110-23 [PMID] 14592764.
View on: PubMed
2001
Presence of oligoclonal T cells in cerebrospinal fluid of a child with multiphasic disseminated encephalomyelitis following hepatitis A virus infection.
Clinical and diagnostic laboratory immunology. 8(5):984-92 [PMID] 11527815.
View on: PubMed

Grants

Jul 2020 – Sep 2020
Sarepta TO #3 – Jess Simple Western System
Role: Principal Investigator
Funding: SAREPTA THERAPEUTICS
Oct 2019 ACTIVE
Treg depletion studies to prove mechanism is immune tolerance
Role: Principal Investigator
Funding: SAREPTA THERAPEUTICS
Oct 2019 ACTIVE
Task Order 6 – Mouse models for continued discovery and determining optimal vector
Role: Principal Investigator
Funding: SAREPTA THERAPEUTICS
Oct 2019 ACTIVE
Sarepta TO #8 – Vector production for in vivo studies to determine candidate
Role: Principal Investigator
Funding: SAREPTA THERAPEUTICS
Oct 2019 ACTIVE
Disease modifying therapy testing in combination with gene therapy
Role: Principal Investigator
Funding: SAREPTA THERAPEUTICS
Sep 2019 ACTIVE
Engineering AAV for safe and efficient gene delivery to the human retina
Role:
Funding: NATL INST OF HLTH NEI
Dec 2018 – Nov 2019
Identifying optimal CD8 Treg for CAR Treg Therapy
Role: Mentor
Funding: AMERICAN SOCIETY OF GENE AND CELL THERAP
Sep 2017 – Nov 2020
Immune modulation and CNS pathology following exogenous a-synuclein challenge
Role:
Funding: NATL INST OF HLTH NINDS
Jan 2017 ACTIVE
Restoring Immune Tolerance in a Model of Multiple Sclerosis
Role: Principal Investigator
Funding: NATL INST OF HLTH NIAID
Apr 2015 – Mar 2019
In Vivo Induction of Antigen Specific T-Cell Tolerance to a Neuro-Antigen by AAV Hepatic Gene Therapy
Role: Principal Investigator
Funding: NATL MULTIPLE SCLEROSIS SOC

Patents

Published April 2015
AAV-Based Gene Therapy for Multiple Sclerosis
#US2017/0043036

Education

PhD Immunology
2006 · Temple University School of Medicine
BS Chemistry & Biology
1994 · University of Central Florida

Teaching Profile

Courses Taught
2018,2020
GMS6253 Molecular Therapy III ? Immunology of Gene Transfer
2019-2020
GMS6034 Advanced Virology I: Genetics and RNA
2016
GMS6024 Princ Neuroscience 4

Contact Details

Phones:
Business:
(352) 273-8152
Emails:
Business:
bhoffman@ufl.edu