A5101199019- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Virus-based gene therapy research
- Hemophilia Treatment and Research
- Nanowire Synthesis and Applications
- Neuroblastoma Research and Treatments
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Erythrocyte Function and Pathophysiology
- RNA modifications and cancer
- Viral gastroenteritis research and epidemiology
- RNA Interference and Gene Delivery
- Cell Image Analysis Techniques
- Transgenic Plants and Applications
- Single-cell and spatial transcriptomics
- Platelet Disorders and Treatments
- Kruppel-like factors research
- Immunodeficiency and Autoimmune Disorders
- Pneumonia and Respiratory Infections
- Blood properties and coagulation
- Epigenetics and DNA Methylation
Children's Hospital of Los Angeles
2021-2024
University of Southern California
2021-2024
Children's Center
2021
APLA Health
2019
University of Pennsylvania
2017
Children's Hospital of Philadelphia
2017
University of Miami
2014
University of Florida
2007-2012
Florida College
2007-2009
University of Florida Health
2007
Abstract The GD2 ganglioside, which is abundant on the surface of neuroblastoma cells, targeted by an FDA-approved therapeutic monoclonal antibody and attractive tumor-associated antigen for cellular immunotherapy. Chimeric receptor (CAR)–modified T cells can have potent antitumor activity in B-cell malignancies, trials to harness this cytolytic toward are under way. In effort enhance CAR that target GD2, we generated variant constructs predicted improve stability affinity GD2-binding,...
Abstract The ability to utilize preclinical models predict the clinical toxicity of chimeric antigen receptor (CAR) T cells in solid tumors is tenuous, thereby necessitating development and evaluation gated systems. Here we found that murine GD2 CAR-T cells, specific for tumor-associated GD2, induce fatal neurotoxicity a costimulatory domain-dependent manner. Meanwhile, human B7H3 exhibit efficacy neuroblastoma. Seeking better CAR, generated SynNotch CAR-T, GD2-B7H3, recognizing as gate...
To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia other inherited deficiencies, we have developed a prophylactic protocol using murine B model. Oral delivery coagulation factor IX fused cholera toxin β-subunit (with without furin cleavage site; CTB-FFIX CTB-FIX), expressed chloroplasts (up to 3.8% soluble 0.4 mg/g leaf tissue), bioencapsulated plant cells, effectively blocked formation...
Immune responses to factor IX (F.IX), a major concern in gene therapy for hemophilia, were analyzed adeno-associated viral (AAV-2) transfer skeletal muscle and liver as function of the F9 underlying mutation. Vectors identical those recently used clinical trials administered four lines hemophilia B mice on defined genetic background [C3H/HeJ with deletion endogenous transgenic range nonfunctional human F.IX (hF.IX) variants]. The strength immune response AAV-encoded inversely correlated...
<div>Abstract<p>Chimeric antigen receptor (CAR) T-cell therapy has remarkably succeeded in treating lymphoblastic leukemia. However, its success acute myeloid leukemia (AML) remains elusive because of the risk on-target off-tumor toxicity to hematopoietic stem/progenitor cells (HSPC) and insufficient persistence longevity. Using a SynNotch circuit, we generated high-precision “IF-THEN” gated logical circuit against combination CD33 CD123 AML antigens demonstrated antitumor...
<p>additional and extended data from stuying constituitive gated CAR-T cells.</p>
<p>Single cell data of the clusters, gene expresion, biomarker and called annotations</p>
Immune checkpoint therapy has resulted in minimal clinical response many pediatric cancers. We sought to understand the influence of immune inhibition using anti-PD-1 and anti-CTLA-4 antibodies individually, combination, after chemotherapy on responses established murine neuroblastoma models. also role tumor microenvironment (TME) PD-L1 expression their alteration post-chemotherapy our models human tissues. was enriched tumor-associated macrophages up-regulated chemotherapy. In a disease...
Intramuscular (IM) administration of an adeno-associated viral (AAV) vector represents a simple and safe method gene transfer for treatment the X-linked bleeding disorder hemophilia B (factor IX, F.IX, deficiency). However, approach is hampered by increased risk immune responses against F.IX. Previously, we demonstrated that drug cocktail suppressants rapamycin, IL-10, specific peptide (encoding dominant CD4(+) T cell epitope) caused induction regulatory cells (Treg) with concomitant...
A subset of patients with severe hemophilia B, the X-linked bleeding disorder resulting from absence coagulation factor IX (FIX), develop pathogenic antibody responses during replacement therapy. These inhibitors block standard therapy and are often associated anaphylactic reactions to FIX. Established clinical immune tolerance induction protocols fail for FIX inhibitors. In a murine model this complication, retrovirally transduced primary B cells expressing antigen fused immunoglobulin-G...
Many genes residing in gene clusters and expressed a differentiation or developmental-stage specific manner are regulated by locus control regions (LCRs). These complex genetic regulatory elements often composed of several DNAse I hypersensitive sites (HS sites) that function together to regulate the expression cis-linked genes. Particularly well characterized is LCR associated with beta-globin locus. The consists five HS located upstream beta-like globin Recent data demonstrate required for...
Upstream stimulatory factor and TFII‐I are ubiquitously expressed helix‐loop‐helix transcription factors that interact with E‐box sequences or initiator elements. We previously demonstrated upstream is an activator of β‐globin gene expression whereas a repressor. In the present study, we demonstrate interacts coactivator p300 this interaction restricted to erythroid cells expressing adult gene. Furthermore, Suz12, component polycomb repressor complex 2, recruited Reducing Suz12 significantly...
CtBP is a transcriptional corepressor with tumorigenic potential that targets the promoter of tumor suppressor gene E-cadherin. Pnn/DRS (Pnn) "nuclear speckle"-associated protein involved in mRNA processing as well regulation E-cadherin via its binding to CtBP. Here, we show can recruit Pnn CtBP-associated complexes, resulting Pnn-dependent chromatin remodeling at promoter. In addition, and differentially modulate splicing, polymerase II serving an interface this event. Therefore, Pnn/CtBP...
Abstract CAR T-cell therapy has remarkably succeeded in treating lymphoblastic leukemia. However, its success AML remains elusive due to the risk of on-target off-tumor toxicity hematopoietic stem and progenitor cells (HSPC) insufficient persistence longevity. Using a SynNotch circuit, we generated high-precision “IF-THEN” gated logical circuit against combination CD33 CD123 antigens demonstrated anti-tumor efficacy cell lines patient-derived xenografts. Unlike constitutively expressed CAR-T...
Transcription factor USF is a ubiquitously expressed member of the helix-loop-helix family proteins. It binds with high affinity to E-box elements and, through interaction coactivators, aids in formation transcription complexes. Previous work demonstrated that regulates genes during erythroid differentiation, including HoxB4 and beta-globin. Here, we show cell-specific expression dominant-negative mutant USF, A-USF, transgenic mice reduces all beta-type globin leads diminished association...
Primary autologous B-lymphocytes, following ex vivo gene transfer and re-implantation, have been successfully utilized to prevent autoimmune disease adaptive responses therapeutic proteins in several animal models. However, efficient primary B cells requires use of retroviral vectors, which increase the risk insertional mutagenesis. Here, we evaluated alternative approaches. Resting splenic were purified activated with LPS, GFP was performed by means nucleofection, lipofectamine, adenoviral...
Differentiation of erythroid cells is regulated by cell signaling pathways including those that change the intracellular concentration calcium. Calcium-dependent proteases have been shown previously to process and regulate activity specific transcription factors. We show here protein levels upstream stimulatory factor (USF) increase during differentiation murine erythroleukemia (MEL) cells. USF was subject degradation Ca(2+)-dependent protease m-calpain in undifferentiated but not...
<h3>Background</h3> TGF-β-targeted CAR-T cells that seek to overcome TME's immunosuppression remain a major opportunity improve current cell therapies. B7-H3, pan-cancer antigen found be highly expressed in many pediatric solid tumors, is currently being explored several trials. Interim reports suggest the treatment was tolerated with mediocre responses. We proposed arm these B7-H3 novel chimeric TGF-β switch receptor (CTSR) convert immunosuppressive signal Toll-like (TLR)-mimicking...