A5034016497- CAR-T cell therapy research
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Hemophilia Treatment and Research
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Transgenic Plants and Applications
- Viral gastroenteritis research and epidemiology
- Viral Infectious Diseases and Gene Expression in Insects
- Virology and Viral Diseases
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- interferon and immune responses
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
- Tropical and Extratropical Cyclones Research
- Cytomegalovirus and herpesvirus research
- Viral Infections and Vectors
- Influenza Virus Research Studies
- Animal Disease Management and Epidemiology
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Neuroinflammation and Neurodegeneration Mechanisms
- Platelet Disorders and Treatments
- SARS-CoV-2 and COVID-19 Research
Indiana University – Purdue University Indianapolis
2018-2025
Indiana University School of Medicine
2019-2023
Palo Alto University
2023
Stanford University
2023
University of Florida
2012-2019
Virginia–Maryland College of Veterinary Medicine
2010-2017
Virginia Tech
2010-2017
National Institute of Immunology
2017
Bangladesh Agricultural University
2016
Dana-Farber Cancer Institute
2012
Newcastle disease virus (NDV), an avian paramyxovirus, is tumor selective and intrinsically oncolytic because of its potent ability to induce apoptosis. Several studies have demonstrated that NDV selectively cytotoxic cells but not normal due defects in the interferon (IFN) antiviral responses cells. Many naturally occurring strains intact IFN-antagonistic function can still replicate human To avoid potential toxicity issues with NDV, especially cancer patients immunosuppression, safe...
Adoptive cell therapy utilizing ex vivo expanded polyclonal CD4+CD25+FOXP3+ regulatory T cells (Treg) is in use clinical trials for the treatment of type 1 diabetes and prevention graft vs host disease bone marrow transplantation. Here we seek to evaluate this approach inherited protein deficiencies, i.e. hemophilia, which often complicated by antibody formation against therapeutic protein. Treg from mice that express GFP-marked FoxP3 were highly purified two-step magnetic/flow sorting 50-...
Carbonic anhydrases (CAs) are ubiquitous enzymes that catalyze the reversible hydration/dehydration of carbon dioxide/bicarbonate. As such, there is enormous industrial interest in using CA as a bio-catalyst for sequestration and biofuel production. However, to ensure cost-effective use enzyme under harsh conditions, studies were initiated produce variants with enhanced thermostability while retaining high solubility catalytic activity. Kinetic structural conducted determine functional...
Inhibitor formation is a serious complication of factor VIII (FVIII) replacement therapy for the X-linked bleeding disorder haemophilia A and occurs in 20%-30% patients. No prophylactic tolerance protocol currently exists. Although we reported oral induction using FVIII domains expressed tobacco chloroplasts, significant challenges clinical advancement include expression full-length CTB-FVIII sequence to cover entire patient population, regardless individual CD4
Regulatory T cells (Tregs) control immune responses in autoimmune disease, transplantation, and enable antigen-specific tolerance induction protein-replacement therapies. Tregs can exert a broad array of suppressive functions through their cell receptor (TCR) tissue-directed manner. This capacity now be harnessed for by "redirecting" polyclonal to overcome low inherent precursor frequencies simultaneously augment functions. With the use hemophilia A as model, we sought engineer suppress...
Hepatic adeno-associated viral (AAV) gene transfer has the potential to cure X-linked bleeding disorder hemophilia A. However, declining therapeutic coagulation factor VIII (FVIII) expression plagued clinical trials. To assess mechanistic underpinnings of this loss FVIII expression, we developed a A mouse model that shares key features observed in Following liver-directed AAV8 presence rapamycin, initial protein declines over time absence antibody formation. Surprisingly, production occurs...
Adeno-associated virus (AAV) vectors are used for correcting multiple genetic disorders. Although the goal is to achieve lifelong correction with a single vector administration, ability redose would enable extension of therapy in cases which initial gene transfer insufficient lasting cure, episomal forms lost growing organs pediatric patients, or transgene expression diminished over time. However, AAV typically induces potent and long-lasting neutralizing antibodies (NAbs) against capsid...
The development of inhibitory antibodies (inhibitors) is a serious complication in the treatment hemophilia A with clotting factor VIII (FVIII) replacement therapy. Inhibitor formation critically depends on T cell help and modulation by regulatory cells (Tregs). In this study, we evaluated F5111 immunocytokine (IC), single chain fusion between human interleukin-2 (IL-2) cytokine an IL-2 antibody that biases activity towards high receptor alpha (IL-2Rα) expression, leading to extended...
Despite over 80 years of clinical experience with coagulation factor (F)VIII inhibitors, surprisingly little is known about the in vivo mechanism this most serious complication replacement therapy for hemophilia A. These neutralizing anti-drug alloantibodies arise ~30% patients. Inhibitor formation T cell-dependent, but events leading up to helper cell activation have been elusive due part complex anatomy and cellular makeup spleen. Here, we show that FVIII antigen presentation CD4+ cells...
The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in vector gene transfer, which often results immune tolerance induction to transgene products. Although the underlying mechanism has been extensively studied, our understanding antigen presentation product-specific CD4+ T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive...
Upon viral infection of the liver, CD8
Newcastle disease virus (NDV), an avian paramyxovirus, is inherently tumor selective and currently being considered as a clinical oncolytic vaccine vector. In this study, we analyzed the effect of complement on neutralization NDV purified from embryonated chicken eggs, common source for production. Fresh normal human serum (NHS) neutralized by multiple pathways activation, independent neutralizing antibodies. Neutralization was associated with C3 deposition activation C2, C3, C4, C5...
Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to among different breeds water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns self antigens through surveillance receptors known as Toll like (TLR). We investigated role TLR cytokines differential PPRV. examined replication PPRV peripheral blood...
Development of antibodies (inhibitors) against coagulation factor VIII (FVIII) is a major complication intravenous replacement therapy in haemophilia A (HA). Current immune tolerance induction (ITI) regimens are not universally effective. Rituximab, B cell-depleting antibody CD20, has shown mixed results for inhibitor reversal patients. This study aims to develop combinatorial HA, using anti-murine CD20 (anti-mCD20) and rapamycin, which targets both T cell responses. Additionally, it...
Innate immune signals that promote B cell responses in gene transfer are generally ill-defined. In this study, we evaluate the effect of activating endosomal Toll-like receptors 7, 8, and 9 (TLR7, TLR7/8, TLR9) on antibody formation during muscle-directed therapy with adeno-associated virus (AAV) vectors. We examined whether activation TLRs, by adenine analog CL264 (TLR7 agonist), imidazolquinolone compound R848 (TLR7/8 or class CpG oligodeoxynucleotides ODN1826 (TLR9 could augment upon...
Limitations to successful gene therapy with adeno-associated virus (AAV) can comprise pre-existing neutralizing antibodies the vector capsid that block cellular entry, or inefficient transduction of target cells lead sub-optimal expression therapeutic transgene. Recombinant serotype 3 AAV (AAV3) is an emerging candidate for liver-directed therapy. In this study, we integrated rational design by using a combinatorial library derived from AAV3B capsids directed evolution in vitro selection...