A5101810224- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Doctoral Education Challenges and Solutions
- Acute Myeloid Leukemia Research
- Chemokine receptors and signaling
- HER2/EGFR in Cancer Research
- Health and Medical Research Impacts
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- Acute Ischemic Stroke Management
- Atrial Fibrillation Management and Outcomes
- Microfluidic and Bio-sensing Technologies
- Nanowire Synthesis and Applications
- Single-cell and spatial transcriptomics
- scientometrics and bibliometrics research
- RNA Interference and Gene Delivery
- Cell death mechanisms and regulation
- Calcium signaling and nucleotide metabolism
- CAR-T cell therapy research
- Neuroethics, Human Enhancement, Biomedical Innovations
- RNA Research and Splicing
- Innovative Microfluidic and Catalytic Techniques Innovation
- Phagocytosis and Immune Regulation
University of Toronto
2016-2021
University Health Network
2018
Stanford University
2016
Weizmann Institute of Science
2016
Shanghai Public Health Clinical Center
2016
University of Pennsylvania
2016
Fate Therapeutics (United States)
2016
California Institute for Biomedical Research
2014-2016
McGill University
2014
Children's National
2006-2013
Significance Chimeric antigen receptor T (CAR-T) cell therapy has produced promising results in clinical trials but been challenged by the inability to control engineered cells once infused into patient. Here we present a generalizable method of controlling CAR-T using peptide-engrafted antibody-based molecular switches that act as bridge between target and cell. We show specific for CD19 govern activity, tissue-homing, cytokine release, phenotype switchable dose-titratable manner xenograft...
Acute myeloid leukemia (AML), which is the most common acute adult and second pediatric leukemia, still has a poor prognosis. Human C-type lectin-like molecule-1 (CLL1) recently identified lineage restricted cell surface marker, overexpressed in over 90% of AML patient blasts leukemic stem cells. Here, we describe synthesis novel bispecific antibody, αCLL1-αCD3, using genetically encoded unnatural amino acid, p-acetylphenylalanine. The resulting αCLL1-αCD3 recruits cytotoxic T cells to CLL1...
Abstract A chemically defined anti‐CXCR4–auristatin antibody–drug conjugate (ADC) was synthesized that selectively eliminates tumor cells overexpressing the CXCR4 receptor. The unnatural amino acid p ‐acetylphenylalanine (pAcF) site‐specifically incorporated into an anti‐CXCR4 immunoglobulin G (IgG) and conjugated to auristatin through a stable, non‐cleavable oxime linkage afford homogeneous ADC. full‐length ADC cytotoxic + cancer in vitro (half maximal effective concentration (EC 50...
Gene expression analysis of individual cells enables characterization heterogeneous and rare cell populations, yet widespread implementation existing single-cell gene techniques has been hindered due to limitations in scale, ease, cost. Here, we present a novel microdroplet-based, one-step reverse-transcriptase polymerase chain reaction (RT-PCR) platform demonstrate the detection three targets simultaneously over 100,000 single experiment with rapid read-out. Our customized reagent cocktail...
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy, but the large number of HSCs required limits its widespread use. Host conditioning and donor composition are known to affect HSCT outcomes. However, specific role that posttransplantation signaling environment plays in HSC fate poorly understood. To mimic clinical HSCT, we injected human umbilical cord blood (UCB) cells at different doses compositions into immunodeficient NOD/SCID/IL-2Rgc-null (NSG) mice....
CD8+ tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling previously shown result from inactivation of p56lck kinase. We identify a novel interacting partner for in nonlytic TIL, Protocadherin-18 ('pcdh18'), and show that pcdh18 is transcribed upon vitro or vivo activation all central memory (CD44+CD62LhiCD127+) coincident with conversion into effector (CD44+CD62LloCD127+). Expression primary induces the phenotype TIL: TCR signaling,...
Microscale technologies offer the capability to generate in vitro artificial cellular microenvironments that recapitulate spatial, biochemical, and biophysical characteristics of native extracellular matrices enable systematic, quantitative, high-throughput studies cell fate their respective environments. We developed a microfluidic platform for generation two-dimensional arrays micrometer-size cell-laden hydrogel modules (HMs) encapsulation culture. Fibroblast cells (NIH 3T3) non-adherent T...
Although the death-inducing signaling complex (DISC) is rapidly assembled, several lines of evidence suggest that formation this not first consequence cell surface CD95 (Fas) stimulation but rather a later step in process. Activation Fas triggers cascade events culminate cellular apoptosis. Tyrosine kinases are critical effectors T activation. However, their functional involvement death receptor-mediated apoptosis unknown. Here, we used p56Lck-deficient cells to show CD95-induced highly...
Abstract A chemically defined anti‐CXCR4–auristatin antibody–drug conjugate (ADC) was synthesized that selectively eliminates tumor cells overexpressing the CXCR4 receptor. The unnatural amino acid p ‐acetylphenylalanine (pAcF) site‐specifically incorporated into an anti‐CXCR4 immunoglobulin G (IgG) and conjugated to auristatin through a stable, non‐cleavable oxime linkage afford homogeneous ADC. full‐length ADC cytotoxic + cancer in vitro (half maximal effective concentration (EC 50...
Abstract Acute myeloid leukemia (AML), which is the most common acute adult and second pediatric leukemia, still has a poor prognosis. Human C‐type lectin‐like molecule‐1 (CLL1) recently identified lineage restricted cell surface marker, overexpressed in over 90 % of AML patient blasts leukemic stem cells. Here, we describe synthesis novel bispecific antibody, αCLL1‐αCD3, using genetically encoded unnatural amino acid, p ‐acetylphenylalanine. The resulting αCLL1‐αCD3 recruits cytotoxic T...
Abstract Regulation of lytic activity in CD8+ CTL remains incompletely understood despite the importance this effector T cell function immune response to intracellular pathogens and tumors. One important aspect involving regulation is spatio-temporal DAG metabolism cells. Based on involvement phospholipase D (PLD) isoforms metabolism-related vesicular trafficking other cells types, we reasoned that these enzymes might regulate By combining use pharmacological inhibitors siRNA-mediated...
T cell receptor (TCR)-induced activation of protein kinase C (PKC) has long been known to be critical for regulation granule exocytosis mediated cytotoxicity in CD8+ cells. However, the mechanism by which PKC regulates this effector function is not clear. In addition, it family members are involved process. By combining use pharmacological inhibitors and mice with targeted gene deletions, we showed that Protein Kinase □elta required lytic mouse CD8+T We studied lysosomal/lytic movements...