A5063063001- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Protease and Inhibitor Mechanisms
- Cancer Genomics and Diagnostics
- Cell Adhesion Molecules Research
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Genomic variations and chromosomal abnormalities
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Genomics and Chromatin Dynamics
- Enzyme Production and Characterization
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Genomics and Rare Diseases
- Carcinogens and Genotoxicity Assessment
- Chronic Myeloid Leukemia Treatments
- TGF-β signaling in diseases
- Hematopoietic Stem Cell Transplantation
- Sarcoma Diagnosis and Treatment
- NF-κB Signaling Pathways
- Hedgehog Signaling Pathway Studies
- Cancer-related Molecular Pathways
Stanford University
2020-2024
St. Jude Children's Research Hospital
2002-2019
Australian National University
1994-2000
Urokinase plasminogen activator receptor (uPAR) gene expression has been implicated in many important biological processes including cell invasiveness and migration. The uPAR was cloned from a human genomic library by hybridization with cDNA. complete structure of the gene, 21.23-kb transcription unit 204 bp 5' 239 3' flanking sequences, determined comparison cDNA sequence. is composed seven exons six introns. 101, 111, 144, 162, 135, 147 563 are separated introns approximately 2.04, 2.62,...
Abstract Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed the development of better treatment regimens. High risk subtypes continue have poor outcomes event free rates <40% despite use high intensity chemotherapy combination hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, vivo efficacy studies identify therapeutic strategies...
We have previously defined the promoter of human urokinase‐type plasminogen activator receptor (uPAR) gene in a 188‐bp fragment between bases −141 and +47 relative to translation start site. Here, we report that novel nuclear factor‐kappaB (NF‐κB)‐like sequence (5′‐GGGAGGAGTC‐3′) at −45 is located uPAR one two DNase I‐protected regions, region I −51 −30. This NF‐κB‐like motif differs positions 7–9 from decameric consensus sequences NF‐κB (5′‐GGGRNNYYCC‐3′ where R indicates A or G, Y C T, N...
Groucho (Gro)/TLE transcriptional corepressors are involved in a variety of developmental mechanisms, including neuronal differentiation. They contain conserved C-terminal WD40 repeat domain that mediates interactions with several DNA-binding proteins. In particular, Gro/TLE1 interacts forkhead transcription factor brain 1 (BF-1; also termed FoxG1). BF-1 is an essential regulator differentiation during cerebral cortex development and represses together Gro/TLE1. Gro/TLE-related gene product...
The modulation of urokinase plasminogen activator receptor (uPAR) gene expression by tumor necrosis factor alpha (TNF alpha), phorbol ester (PMA) and amiloride was studied in three colon cancer cell lines. uPAR mRNA protein were induced TNF PMA but inhibited at concentrations 0.1 to 1 mM the presence or absence PMA. Nuclear run-on transcription assay indicated that effects mediated least part transcriptional level, whereas may act via a posttranscriptional mechanism. These results suggested...
An 8.5-kb 5'-flanking region of the human urokinase-type plasminogen activator receptor (uPAR) gene was cloned and detailed uPAR promoter defined in an 188-bp fragment between bases -141 +47 relative to transcription-start site. 5'-Deletion -100 -60 abolished its activity, indicating that 81-bp segment -61, which contains a proximal AP-1 site at position -70, is required for activity. Nuclear extracts from HCT116 cells contain proteins specifically bind Mutation motif reduced activity...
The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) chromosomal translocation in leukemic pro-B cells, encodes a chimeric transcription factor consisting of transactivation domain E2A linked to bZIP DNA-binding and protein dimerization hepatic leukemia (HLF). This oncoprotein blocks apoptosis induced growth deprivation or irradiation, but mechanism for this effect remains unclear. We therefore performed representational difference analysis (RDA) identify downstream genetic targets...
Abstract IGH@ proto-oncogene translocation is a common oncogenic event in lymphoid lineage cancers such as B-ALL, lymphoma and multiple myeloma. Here, to investigate the interplay between IGH allelic exclusion, we perform long-read whole-genome transcriptome sequencing along with epigenetic 3D genome profiling of Nalm6, an - DUX4 positive B-ALL cell line. We detect significant imbalance on wild-type over haplotype expression data, showing occurs silenced allele. In vitro, this reduces stress...
The effects of butyrate on the modulation urokinase plasminogen activator (uPA) and its receptor (uPAR) mRNAs were studied. While both mRNA levels increased after stimulation by tumor necrosis factor alpha (TNF alpha), phorbol ester (PMA) cycloheximide, they inhibited at 2.5 to 25 mM. Nuclear run-on transcription assays indicated that uPA was modulated transcriptional level but uPAR gene regulated post-transcriptional in presence or absence TNF alpha. In PMA, however, acts genes.
Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute leukemia or, the absence bone marrow involvement. We identified an infant isolated whose was negative for involvement by flow cytometry. Sequencing revealed fusion oncogene CIC-NUTM2A and to be clonally evolved from marrow, which carried despite pathology. Murine modeling confirmed ability transform hematopoietic cells receptor tyrosine kinase (RTK) signaling activation consistent...
CBFA2T3-GLIS2 is a fusion oncogene found in pediatric acute megakaryoblastic leukemia that associated with poor prognosis. We establish model of driven allows the distinction specific changes from those reflect megakaryoblast lineage this leukemia. Using model, we map genome wide binding turn imparts characteristic transcriptional signature. A network transcription factor genes bound and upregulated by are to have downstream effects result dysregulated signaling developmental pathways...
In humans and in mouse models, precursor B-cell lymphoblastic leukemia (B-ALL)/lymphoblastic lymphoma (B-LBL) can be classified as either the pro-B or pre-B subtype. This is based on expression of antigens associated with stages development. Antigenic markers detected by flow cytometry immunohistochemistry (IHC), but no comparison results from these techniques has been reported for murine B-ALL/LBL. our analysis 30 cases induced chemical viral mutagenesis a WT Pax5 +/– background, 18 (60%)...