Brad E. Hoffman, Ph.D.
Cancer & Genetics Research Complex
2033 Mowry Road
Dr. Hoffman is a cellular immunologist with a major interest in immune modulation and tolerance induction using adeno-associated virus (AAV) gene therapy. Dr. Hoffman earned his Ph.D. in Immunology from Temple University School of Medicine in 2006. He subsequently performed postdoctoral research in gene therapy at University of Florida. In 2010, he received the Kokomoor Award for Excellence in Pediatric Research and became an Assistant Professor of Pediatrics in the Division of Cellular & Molecular Therapy. Dr. Hoffman’s research has earned him multiple awards and grants, including an American Heart Association Fellowship (2007), Pfizer Award in Hemophilia Research (ASPIRE, 2011), BD Bioscience Immunology Award (2011), Children’s Miracle Network grant (2012-13), National Multiple Sclerosis Society Pilot grant (2014), and research grant (2015). He is also a NIH – Pediatric Research LRP Recipient (2012-14).
- Postdoctoral Training, University of Florida, College of Medicine
- Ph.D. – Microbiology and Immunology, Temple University, School of Medicine
- B.S. – Chemistry & Biology , University of Central Florida
My research group is particularly interested in the mechanisms surrounding the generation of antigen-specific regulatory T-cells (Tregs), and the role they have in tolerance induction following gene transfer. Our major focus is aimed at exploiting the unique molecular and cellular mechanisms of liver-directed AAV gene therapy in order to re-establish immunological self-tolerance to a protein through the induction and expansion of antigen-specific regulatory T-cells. Through an innovative strategy, our group seeks to develop a clinically relevant therapy that will abrogate the progression of autoimmune neurological diseases such as Multiple Sclerosis.
- Keeler GD, Markusic DM, Hoffman BE. Liver induced transgene tolerance with AAV vectors. Cell Immunol. 2019 Aug; 10.1016/j.cellimm.2017.12.002. https://www.ncbi.nlm.nih.gov/pubmed/2957635
- Keeler GD, Kumar S, Palaschak B, Silverberg EL, Markusic DM, Jones NT, Hoffman BE. Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis. Mol Ther. 2018 Jan 3;26(1):173-183. Epub 2017 Sep 21. PubMed https://www.ncbi.nlm.nih.gov/pubmed/28943274
- Hoffman BE*, Kumar SRP*, Terhorst C, de Jong YP, Herzog RW. The Balance between CD8+ T Cell-Mediated Clearance of AAV-Encoded Antigen in the Liver and Tolerance Is Dependent on the Vector Dose. Mol Ther 2017, 25(4): 880-891.*co-first author. https://www.ncbi.nlm.nih.gov/pubmed/28284982
- Herzog RW, Cooper M, Perrin GQ, Biswas M, Martino AT, Morel L, Terhorst C, Hoffman BE. Regulatory T cells and TLR9 activation shape antibody formation to a secreted transgene product in AAV muscle gene transfer. Cell Immunol 2017. https://www.ncbi.nlm.nih.gov/pubmed/28888664
- Krotova K, Marek GW, Wang RL, Aslanidi G, Hoffman BE, Khodayari N, Rouhani FN, Brantly ML. Alpha-1 Antitrypsin-Deficient Macrophages Have Increased Matriptase-Mediated Proteolytic Activity. Am J Respir Cell Mol Biol 2017, 57(2): 238-247. https://www.ncbi.nlm.nih.gov/pubmed/28362108
- Rogers GL, Shirley JL, Zolotukhin I, Kumar SRP, Sherman A, Perrin GQ, Hoffman BE, Srivastava A, Basner-Tschakarjan E, Wallet MA, Terhorst C, Biswas M, Herzog RW. Plasmacytoid and conventional dendritic cells cooperate in crosspriming AAV capsid-specific CD8(+) T cells. Blood 2017, 129(24): 3184-3195; https://www.ncbi.nlm.nih.gov/pubmed/28468798
- Hoffman, B.E., Vercauteren, K., Zolotukhin, I., Keeler, G.D., Xiao, J.W., Basner-Tschakarjan, E., High, K.A., Ertl, H.C., Rice, C.M., Srivastava, A., de Jong, Y.P. and Herzog, R.W., Superior in vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid. Molecular Therapy, 2016. 24 p.1042-6. http://www.ncbi.nlm.nih.gov/pubmed/27019999
- Xiao, Y., Kwon, Hoffman, B.E., K.C., Kamesh, A., Jones, N.T., Herzog, R.W. and Daniell, H., Low cost delivery of proteins bioencapsulated in plant cells to human non-immune or immune modulatory cells. Biomaterials, 2016. 80: p. 68-79. http://www.ncbi.nlm.nih.gov/pubmed/26706477
- Zolotukhin I, Markusic DM, Palaschak B, Hoffman BE, Srikanthan MA, Herzog RW. Potential for cellular stress response to hepatic factor VIII expression from AAV vector. Mol Ther Methods Clin Dev 2016, 3: 16063. https://www.ncbi.nlm.nih.gov/pubmed/27738644
- Wang, X., Su, J., Sherman, A., Rogers, G.L., Liao, G., Hoffman, B.E., Leong, K.W., Terhorst, C., Daniell, H. and Herzog, R.W., Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells. Blood, 2015. 125(15): p. 2418-27. http://www.ncbi.nlm.nih.gov/pubmed/25700434