A5067513341- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Immunodeficiency and Autoimmune Disorders
- Retinoids in leukemia and cellular processes
- Lymphoma Diagnosis and Treatment
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Nitric Oxide and Endothelin Effects
- Cellular transport and secretion
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Lysosomal Storage Disorders Research
University of Chicago
2011-2024
San Francisco Foundation
2002-2005
University of California, San Francisco
2002-2005
University of Toronto
1996-2001
University Health Network
2000-2001
Princess Margaret Cancer Centre
2001
Ontario Institute for Cancer Research
1998-1999
University of Oxford
1998
Cancer Institute (WIA)
1998
Wellesley College
1997
B cell antigen receptor (BCR) association with lipid rafts, the actin cytoskeleton, and clathrin-coated pits influences signaling presentation. Although all three cellular structures have been separately implicated in BCR internalization, relationship between them has not clearly defined. In this study, internalization pathways were characterized by specifically blocking each potential mechanism of internalization. uptake was reduced approximately 70% cells conditionally deficient clathrin...
Abstract The B lymphocyte adaptor molecule of 32 kDa (Bam32) is an that plays indispensable role in BCR signaling. In this study, we found upon ligation, Bam32 recruited to the plasma membrane where it associates with complexes and redistributes internalizes BCRs. ligation induced colocalization lipid rafts, clathrin, actin filaments. An inhibitor Src family protein tyrosine kinases (PTKs) blocked both BCR-induced phosphorylation internalization. Moreover, internalization impaired Bam32−/−...
Abstract Therapy-related myeloid neoplasms (t-MN) following treatment with alkylating agents are characterized by a del(5q), complex karyotypes, alterations of TP53, and dismal prognosis. To decipher the molecular pathway(s) leading to pathogenesis del(5q) t-MN effect(s) cytotoxic therapy on marrow microenvironment, we developed mouse model loss two key genes, EGR1 APC, in hematopoietic cells. We used well-characterized drug, N-ethyl-N-nitrosurea (ENU), demonstrate that agent exposure...
The control of mRNA stability plays a central role in orchestrating gene-regulatory networks hematopoietic cell growth, differentiation and tumorigenesis. HNRNPA0, which encodes an RNA-binding protein shown to regulate transcript via binding the AU-rich elements mRNAs, is located within commonly deleted segment 5q31.2 myeloid neoplasms with del(5q), expressed at haploinsufficient levels these patients. We show that HNRNPA0 normally highly stem cells exhibits dynamic changes expression during...
CD22 is a B cell-restricted glycoprotein involved in cell adhesion and signaling. Since likely to play an important role interactions between cells other cells, regulating signaling thresholds, we characterized the expression of murine during different stages development. In contrast previous reports, show that expressed on progenitors prior IgM. IL-7-responsive precursors from fetal liver early lineage (B220+IgM-) bone marrow both express low density surface CD22. The majority earliest...
9-O-Acetylation is one of the most common modifications sialic acids, and it can affect several acid-mediated recognition phenomena. We previously reported a cDNA encoding lysosomal acid-specific 9-O-acetylesterase, which traverses endoplasmic reticulum-Golgi pathway localizes primarily to lysosomes endosomes. In this study, we report variant derived from same gene that contains different 5′ region. This has putative open reading frame lacking signal peptide-encoding sequence thus candidate...
Abstract The proliferation, survival, and differentiation of B cell progenitors in primary hematopoietic tissues depends on extracellular signals produced by stromal cells within the microenvironment. IL-7 is a stromal-derived growth factor that plays crucial role lineage development. We have shown presence IL-7, pro-B proliferate differentiate to stage which they are responsive LPS, leading terminally differentiated IgM-secreting plasma cells. In this report, we examine detail transition...
Summary: Considerable progress has been made in defining intermediate stages the process leading from stem cells to mature B cells. Cell‐bound and secreted molecules direct progression through these regulate selection of clones which immune repertoire emerges. In fact, a myriad signals derived B‐cell progenitors themselves microenvironment they develop differentiation process. These are provided by antigen receptors (BCR) their surrogates, adhesion cytokine receptors. The co‐operation...
We studied the effects of administrating nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), or precursor, L-arginine, on hemodynamic variables and serum nitrate concentrations in an anesthetized ovine model endotoxemia to assess regional visceral blood flow determine whether L-arginine availability limits production. Animals received Escherichia coli endotoxin (2 micrograms/kg) followed 2 h later by L-NAME (25 mg/kg), (0.575 g/kg), saline administered over 1 infusion...
Therapy-related myeloid neoplasm (t-MN) is a distinctive clinical syndrome occurring after exposure to chemotherapy or radiotherapy. t-MN arises in most cases from multipotential hematopoietic stem cell or, less commonly, lineage committed progenitor cell. The prognosis for patients with poor, as current forms of therapy are largely ineffective. Cytogenetic analysis, molecular analysis and gene expression profiling has revealed that there distinct subtypes the disease; however, our...
We describe the isolation of a cDNA encoding murine sialic acid-specific 9-O-acetylesterase as well its expression pattern in cells both hematopoietic and non-hematopoietic origin. This enzyme catalyzes removal O-acetyl ester groups from position 9 parent acid N-acetylneuraminic acid. The is 2105 nt length encodes protein 541 amino acids with predicted molecular weight 61 kDa, not including oligosaccharides linked to eight potential N-glycosylation sites. acetylesterase displays widespread...
Numerous studies have demonstrated that B lymphopoiesis is dependent upon a stromal cell microenvironment. Many of the cell-derived factors and surface interactions regulate development been identified; however, little consideration has paid to intimate known occur among precursors themselves in both fetal liver marrow microenvironments. In this study we show homotypic between play an important role promoting mature cells. We used vitro assay system demonstrate function cells can be replaced...
Abstract Monosomy 7 (-7) or del(7q) are recurrent in high-risk myeloid neoplasms, including up to 50% of neoplasms arising after prior exposure chemotherapy and/or radiation. Although putative chromosome tumor suppressor genes have been identified, the effects combinatorial 7q gene loss remain unclear. A barrier understanding pathogenesis -7/del(7q) is challenge modeling aneuploidy animal models. To address this knowledge gap, we established an vivo model clonal hematopoiesis and drug...