A5018193219- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Eosinophilic Disorders and Syndromes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Quinazolinone synthesis and applications
- Fungal Plant Pathogen Control
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Physiological and biochemical adaptations
- Genetics, Aging, and Longevity in Model Organisms
- Environmental Science and Water Management
- Plant Genetic and Mutation Studies
- Carcinogens and Genotoxicity Assessment
- Cytokine Signaling Pathways and Interactions
- Genetic Syndromes and Imprinting
University of North Carolina at Chapel Hill
2013-2021
Lewis Clark State College
2021
Oregon Health & Science University
2002-2013
Portland VA Medical Center
2004-2006
Howard Hughes Medical Institute
2003-2006
Leipzig University
2005
Brigham and Women's Hospital
2005
Harvard University
2005
Ariadne Diagnostics (United States)
2004
Hammersmith Hospital
2003
Abstract Imatinib, a Bcr-Abl tyrosine kinase inhibitor, is highly effective therapy for patients with chronic myelogenous leukemia (CML). Despite durable responses in most phase patients, relapses have been observed and are much more prevalent advanced disease. The common mechanism of acquired imatinib resistance has traced to domain mutations decreased sensitivity. Thus, alternate inhibitors that activity against imatinib-resistant mutants would be useful who relapse on therapy. Two such...
Kinase domain (KD) mutations of Bcr-Abl interfering with imatinib binding are the major mechanism acquired resistance in patients Philadelphia chromosome-positive leukemia. Mutations ATP loop (p-loop) have been associated a poor prognosis. We compared transformation potency five common KD mutants various biological assays. Relative to unmutated (native) Bcr-Abl, Y253F and E255K exhibited increased potency, M351T H396P were less potent, performance T315I was assay dependent. The correlated...
Chronic myeloid leukemia (CML) is effectively treated with imatinib. However, reactivation of Bcr-Abl via kinase domain mutations that reduce sensitivity to imatinib can cause relapse. As combination therapy frequently used prevent emergence resistance, the an inhibitor imatinib-resistant mutants (e.g., Src/Abl inhibitors AP23848 and BMS-354825) was investigated.To test this approach, cellular proliferation tyrosine phosphorylation assays were done on Ba/F3 cells expressing wild-type (WT)...
Mammalian DNA replication initiates at multiple sites along chromosomes different times, following a temporal program. Homologous alleles typically replicate synchronously; however, mono-allelically expressed genes such as imprinted genes, allelically excluded and on the female X chromosome asynchronously. We have used engineering strategy to identify human autosomal locus that controls this timing program in cis . show Cre/loxP-mediated rearrangements discrete 6q16.1 result delayed of...
Mammalian chromosomes initiate DNA replication at multiple sites along their length during each S phase following a temporal program. The majority of genes on homologous replicate synchronously. However, mono-allelically expressed such as imprinted genes, allelically excluded and female X asynchronously. We have identified cis-acting locus human chromosome 6 that controls this replication-timing This encodes large intergenic non-coding RNA gene named Asynchronous Autosomal 6, or ASAR6....
The Bloom syndrome helicase, BLM, has numerous functions that prevent mitotic crossovers. We used unique features of Drosophila melanogaster to investigate origins and properties crossovers occur when BLM is absent. Induction lesions block replication forks increased crossover frequencies, consistent with for in responding fork blockage. In contrast, treatment hydroxyurea, which stalls forks, did not elevate crossovers, even though mutants lacking are sensitive killing by this agent. To...
Abstract The absence of functional BLM DNA helicase, a member the RecQ family helicases, is responsible for rare human disorder Bloom Syndrome, which results in developmental abnormalities, repair defects, genomic instability, and predisposition to cancer. In Drosophila melanogaster, orthologous Blm protein essential during early development when embryo under control maternal gene products. We show that lack syncytial cell cycles embryonic severe nuclear defects lethality. Amongst small...
Supplementary Figure 2 from <i>In vitro</i> Activity of Bcr-Abl Inhibitors AMN107 and BMS-354825 against Clinically Relevant Imatinib-Resistant Abl Kinase Domain Mutants
Supplementary Figure 1 from <i>In vitro</i> Activity of Bcr-Abl Inhibitors AMN107 and BMS-354825 against Clinically Relevant Imatinib-Resistant Abl Kinase Domain Mutants
<div>Abstract<p>Imatinib, a Bcr-Abl tyrosine kinase inhibitor, is highly effective therapy for patients with chronic myelogenous leukemia (CML). Despite durable responses in most phase patients, relapses have been observed and are much more prevalent advanced disease. The common mechanism of acquired imatinib resistance has traced to domain mutations decreased sensitivity. Thus, alternate inhibitors that activity against imatinib-resistant mutants would be useful who relapse on...
<div>Abstract<p>Imatinib, a Bcr-Abl tyrosine kinase inhibitor, is highly effective therapy for patients with chronic myelogenous leukemia (CML). Despite durable responses in most phase patients, relapses have been observed and are much more prevalent advanced disease. The common mechanism of acquired imatinib resistance has traced to domain mutations decreased sensitivity. Thus, alternate inhibitors that activity against imatinib-resistant mutants would be useful who relapse on...