A5024703985- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Mesenchymal stem cell research
- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- Acute Lymphoblastic Leukemia research
- Cancer-related gene regulation
- Developmental Biology and Gene Regulation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Erythrocyte Function and Pathophysiology
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer-related molecular mechanisms research
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Hemoglobinopathies and Related Disorders
BC Cancer Agency
2014-2023
Terry Fox Research Institute
2006-2023
University of British Columbia
2012-2022
International Society for Experimental Hematology
2011-2021
Medizinische Hochschule Hannover
2010-2018
Goethe University Frankfurt
2018
Wrexham University
2015
Health Affairs
2011
University of Toronto
2008
Ontario Institute for Cancer Research
2008
A 145-kDa tyrosine-phosphorylated protein that becomes associated with Shc in response to multiple cytokines has been purified from the murine hemopoietic cell line B6SUtA1. Amino acid sequence data were used clone cDNA encoding this a B6SUtA1 library. The predicted amino encodes unique containing an N-terminal src homology 2 domain, two consensus sequences are targets for phosphotyrosine binding domains, proline-rich region, and motifs highly conserved among inositol polyphosphate...
Hox genes were first recognized for their role in embryonic development and may also play important lineage-specific functions a variety of somatic tissues including the hematopoietic system. We have recently shown that certain members A B clusters, such as HOXB3 HOXB4, are preferentially expressed subpopulations human bone marrow highly enriched most primitive cell types. To assess these regulating proliferation and/or differentiation cells, we engineered overexpression HOXB4 murine cells...
Sickle cell disease (SCD) is caused by a single point mutation in the human β A globin gene that results formation of an abnormal hemoglobin [HbS (α 2 S )]. We designed variant prevents HbS polymerization and introduced it into lentiviral vector we optimized for transfer to hematopoietic stem cells expression adult red blood lineage. Long-term (up 10 months) was achieved, without preselection, all transplanted mice with erythroid-specific accumulation antisickling protein up 52% total 99%...
SHIP is a 145-kD SH 2-containing i nositol-5- p hosphatase widely expressed in hemopoietic cells. It was first identified as tyrosine phosphoprotein associated with Shc response to numerous cytokines. has been implicated FcγRIIB receptor-mediated negative signaling B cells and mast postulated down-regulate cytokine signal transduction myeloid To define further its role the proliferation differentiation of progenitors, well function mature cells, we have generated embryonic stem mice bearing...
Multipotential hematopoietic progenitor cell lines have been established from nonadherent populations removed continuous mouse bone marrow cultures. Clonal sublines of B6SUtA or B6JUt derived single cells formed mixed colonies containing erythroid cells, neutrophil-granulocytes, and basophil/mast in semisolid medium erythropoietin conditioned pokeweed mitogen-stimulated spleen cells. Each several subclones line Ro cl eosinophils, medium. Multipotentiality was maintained vitro for over 2 1/2...
Class I homeobox (Hox) genes encode a major group of transcription factors controlling embryonic development and have been implicated in the continuing process hematopoietic cell differentiation. They are clustered on four chromosomes and, early development, exhibit spatially restricted expression with respect to their 3'-->5' chromosomal position. By using an improved PCR-based method for amplifying total cDNA derived from limited numbers, we now describe class Hox highly purified CD34+...
The small number of hematopoietic stem and progenitor cells in cord blood units limits their widespread use human transplant protocols. We identified a family chemically related molecules that stimulates the expansion ex vivo capable reconstituting hematopoiesis for at least 6 months immunocompromised mice. potent activity these newly compounds, UM171 being prototype, is independent suppression aryl hydrocarbon receptor, which targets with more-limited regenerative potential. properties make...
5-Azacytidine is a cytidine analogue that capable of activating repressed genes in tissue-culture cells and has been shown to increase hemoglobin-F production anemic baboons. This drug was administered patient with severe beta-thalassemia an attempt stimulate production. After seven days 5-azacytidine treatment, gamma-globin synthesis increased approximately sevenfold, temporarily normalizing the patient's unbalanced globin synthesis. Erythropoiesis became more effective, leading temporary...
Although hematopoiesis is known to originate in a population of very primitive cells with both lymphopoietic and myelopoietic potential, procedure for enumerating such has date not been available. We now describe quantitative assay long-term repopulating stem the potential reconstituting all hematopoietic lineages. This two key features. The first use competitive repopulation conditions that ensure only detection class but also survival lethally irradiated mice transplanted low numbers...
AbstractMultiple members of the A, B, and C clusters Hox genes are expressed in hematopoietic cells. Several these have been found to display distinctive expression patterns, with located at 3′ side being their highest levels most primitive subpopulation human CD34+ bone marrow cells 5′ end having a broader range expression, downregulation later stages differentiation. To explore if patterns reflect different functional activities, we retrovirally engineered overexpression 5′-located gene,...
To clarify the role that src homology 2-containing inositol phosphatase (SHIP) plays in mast cell degranulation, gene for SHIP was disrupted by homologous recombination embryonic stem cells. Bone-marrow-derived cells from SHIP+/+, +/−, and −/− F 2 littermates were compared. SHIP−/− found to be far more prone after crosslinking of IgE preloaded cells, than SHIP+/− or +/+ Intriguingly, alone also stimulated massive degranulation but not This with alone, which may due low levels aggregates,...