A5070353655- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Virus-based gene therapy research
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Acute Lymphoblastic Leukemia research
- Nuclear Structure and Function
- Herpesvirus Infections and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Extracellular vesicles in disease
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Cytomegalovirus and herpesvirus research
- Chronic Myeloid Leukemia Treatments
- Protein Degradation and Inhibitors
- Blood disorders and treatments
- Lymphoma Diagnosis and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Telomeres, Telomerase, and Senescence
Icahn School of Medicine at Mount Sinai
2017-2024
Tisch Cancer Institute
2022-2023
Tisch Hospital
2022
Cancer Institute (WIA)
2022
Stem Cell Institute
2022
Shanghai Cell Therapy Research Institute
2011-2015
Memorial Sloan Kettering Cancer Center
2008-2014
CD19 CAR T cell therapy induces complete remissions in 88% of 16 adult patients with relapsed or refractory acute lymphoblastic leukemia.
Five adults with chemotherapy-refractory B-ALL were induced into molecular remissions after treatment CD19 CAR-targeted T cells.
On the basis of promising preclinical data demonstrating eradication systemic B-cell malignancies by CD19-targeted T lymphocytes in vivo severe combined immunodeficient-beige mouse models, we are launching phase I clinical trials patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia. We present here validation bioprocess which developed for production expansion grade autologous cells derived from CLL. demonstrate that genetically modified a replication-defective...
Background: LNK/SH2B3 inhibits Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling by hematopoietic cytokine receptors. Genome-wide association studies have shown a common single nucleotide polymorphism in LNK (R262W, T allele) with neutrophilia, thrombocytosis, coronary artery disease. We that LNK(TT ) reduces function LNK-deficient mice display prominent platelet–neutrophil aggregates, accelerated atherosclerosis, thrombosis. Platelet–neutrophil interactions...
The successful genetic engineering of patient T cells with γ-retroviral vectors expressing chimeric antigen receptors or T-cell for phase II clinical trials and beyond requires the large-scale manufacture high-titer vector stocks. production retroviral from stable packaging cell lines using roller bottles 10- to 40-layer factories is limited by a narrow harvest window, labor intensity, open-system operations, requirement significant incubator space. To circumvent these shortcomings, we...
Clonal hematopoiesis (CH) has emerged as an independent risk factor for atherosclerotic cardiovascular disease, with activation of macrophage inflammasomes a potential underlying mechanism. The NLRP3 (NLR family pyrin domain containing 3) inflammasome key role in promoting atherosclerosis mouse models
Noninvasive imaging technologies have the potential to enhance monitoring and improvement of adoptive therapy with tumor-targeted T lymphocytes. We established an methodology for assessment spatial temporal distributions adoptively transferred genetically modified human cells in vivo treatment prediction tumor response a systemic prostate cancer model.RM1 murine carcinoma tumors transduced prostate-specific membrane antigen (hPSMA) Renilla luciferase reporter gene were SCID/beige mice. Human...
Connecting specific cancer genotypes with phenotypes and drug responses constitutes the central premise of precision oncology but is hindered by genetic complexity heterogeneity primary cells. Here, we use patient-derived induced pluripotent stem cells (iPSCs) CRISPR/Cas9 genome editing to dissect individual contributions two recurrent lesions, splicing factor SRSF2 P95L mutation chromosome 7q deletion, development myeloid malignancy. Using a comprehensive panel isogenic iPSCs-with none,...
Mutations in splicing factors (SF) are the predominant class of mutations myelodysplastic syndrome (MDS), but convergent downstream disease drivers remain elusive. To identify common direct targets missplicing by mutant U2AF1 and SRSF2, we performed RNA sequencing enhanced version cross-linking immunoprecipitation assay human hematopoietic stem/progenitor cells derived from isogenic induced pluripotent stem cell (iPSC) models. Integrative analyses alternative differential binding converged...
Retroviral vectors derived from the Moloney murine leukemia virus have been used in successful and promising gene therapy clinical trials. However, platforms for their large-scale production must be further developed. As a proof of principle, we reported generation packaging cell line that produces amphotropic retroviral suspension serum-free medium (SFM). In present study, constructed characterized two lines designed transfer hematopoietic cells. These grow SFM, produce high-titer RD114-...
SF3B1K700E is the most frequent mutation in myelodysplastic syndrome (MDS), but mechanisms by which it drives MDS pathogenesis remain unclear. We derived a panel of 18 genetically matched SF3B1K700E- and SF3B1WT-induced pluripotent stem cell (iPSC) lines from patients with ring sideroblasts (MDS-RS) harboring isolated mutations performed RNA ATAC sequencing purified CD34+/CD45+ hematopoietic stem/progenitor cells (HSPCs) them. developed novel computational framework integrating splicing...
The herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene is widely used as a suicide in combination with ganciclovir (GCV) and nuclear imaging reporter an appropriate probe. Wild-type HSV1-tk recognizes variety of pyrimidine acycloguanosine nucleoside analogs, including clinically antiviral drugs. PET expression will be compromised patients receiving nucleoside-based treatment. With the use acycloguanosine-specific mutant enzyme, can successfully performed acycloguanosine-based...
TPS4700 Background: Based on our preclinical animal models, we initiated a phase I dose-escalating study to assess safety, dose requirement and targeting efficiency of genetically directed autologous human T cells targeted Prostate Specific Membrane Antigen (PSMA). Our approach is based the infusion PSMA-targeted utilizing P28z second generation chimeric antigen receptor (CAR) in patients (pts) with metastatic CRPC, following iv cyclophosphamide (Cy) (trial NCT01140373). For herpes simplex...
Spliceosome machinery mutations are common early in myeloid malignancies; however, effective targeted therapies against them still lacking. In the current study, we used an