A5002901530- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Invertebrate Immune Response Mechanisms
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Response and Inflammation
- Virus-based gene therapy research
- Erythrocyte Function and Pathophysiology
- NF-κB Signaling Pathways
- CRISPR and Genetic Engineering
- interferon and immune responses
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- CAR-T cell therapy research
- Insect Resistance and Genetics
- Insect symbiosis and bacterial influences
- Immunotherapy and Immune Responses
- Chronic Myeloid Leukemia Treatments
- Genomics and Chromatin Dynamics
- Neurobiology and Insect Physiology Research
- Bioinformatics and Genomic Networks
- Erythropoietin and Anemia Treatment
- Ubiquitin and proteasome pathways
Duke University
2011-2020
Duke Medical Center
2010-2013
Duke University Hospital
2010-2013
Howard Hughes Medical Institute
2006-2011
Harvard University
1995-2007
Dana-Farber Cancer Institute
1991-2004
Boston Children's Museum
1997
Kantonsspital Baselland
1997
Boston Children's Hospital
1989-1997
Children's Hospital
1992-1997
The hallmark of human cancer is heterogeneity, reflecting the complexity and variability vast array somatic mutations acquired during oncogenesis. An ability to dissect this identify subgroups that represent common mechanisms disease, will be critical understanding complexities genetic alterations provide a framework develop rational therapeutic strategies. Here, we describe classification scheme for breast making use patterns pathway activity build on previous subtype characterizations...
Neuronal cells express a pp60c-src variant that displays an altered electrophoretic mobility and different V8 peptide pattern relative to expressed in tissues of non-neuronal origin. To determine whether the neuronal form is encoded by brain-specific messenger RNA, mouse brain complementary DNA (cDNA) library was screened with chicken c-src probe 3.8-kilobase cDNA clone isolated. This encodes 60-kilodalton protein differs from or human primarily having six extra amino acids...
Among several tyrosine-protein kinases, only v-abl could abrogate interleukin 3 dependence of a lymphoblastoid cell line; v-src and v-fps proteins gave partial or no independence, respectively. Lymphokine independence was achieved via nonautocrine mechanism. Direct involvement c-myc in this process not evident.
A body of evidence has shown that the control E2F transcription factor activity is critical for determining cell cycle entry and proliferation. However, an understanding precise determinants this control, including role other cell-cycle regulatory activities, not been clearly defined. Here, recognizing contributions individual components could be masked by heterogeneity in populations cells, we model potential roles together with use integrated system to follow dynamics at single-cell level...
The human interleukin 3 (IL-3) promoter is comprised of several cis-acting DNA sequences that modulate T-cell expression IL-3. These are located within 315 nucleotides upstream the mRNA start site. Transient reporter genes linked to serially deleted IL-3 has allowed mapping two activator and an interposed repressor sequence. proximal regulatory region specific prerequisite for efficient transcription. Its effect enhanced by a second, more distal activating sequence consisting AP-1 binding...
The length of the G1 phase in cell cycle shows significant variability different types and tissue types. To gain insights into control length, we generated an E2F activity reporter that captures free after dissociation from Rb sequestration followed its kinetics activation at single-cell level, real time. Our results demonstrate is precisely coordinated with S progression. Quantitative analysis indicates there a pre-S delay between transcriptional dynamic dynamics. This variable among...
Ectopic expression of the erythropoietin receptor (EPO-R) in Ba/F3, an interleukin 3-dependent progenitor cell line, confers EPO-dependent growth. To examine whether introduced EPO-R could affect differentiation, we isolated Ba/F3-EPO-R subclones 3 and assayed for induction beta-globin mRNA synthesis after exposure to EPO. Detection was observed within days EPO treatment, with peak levels accumulating 10 days. When withdrawn, persisted most clones, suggesting that commitment erythroid...
The erythropoietin receptor (EPO-R), a member of the cytokine superfamily, can be activated by binding either (EPO) or gp55, Friend spleen focus-forming virus glycoprotein. highly specific interaction between gp55 and EPO-R triggers cell proliferation thereby causes first stage virus-induced erythroleukemia. We have generated functional chimeric receptors containing regions interleukin-3 (AIC2A polypeptide), related which does not interact with gp55. All were expressed at similar levels, had...
Two temperature-sensitive mutants of Fujinami sarcoma virus were isolated and characterized. Cells infected with the temperature sensitive in focus formation, colony increased sugar uptake, synthesis plasminogen activator. The changes between transformed nontransformed states cultures completely reversible by shifting temperature. A virus-specific protein 130,000 daltons, p130, was synthesized mutant-infected cells regardless temperature, but immunoprecipitates p130 from extracts active...
FlyRNAi (http://www.flyrnai.org), the database and website of Drosophila RNAi Screening Center (DRSC) at Harvard Medical School, serves a dual role, tracking both production reagents for RNA interference (RNAi) screening in cells screen results. The is used as platform community availability protocols, tools, other resources useful to researchers planning, conducting, analyzing or interpreting results screens. Based on our own experience user feedback, we have made several changes....
The temporal activation of kinases and timely ubiquitin-mediated degradation is central to faithful mitosis. Here we present evidence that acetylation controlled by Coenzyme A synthase (COASY) acetyltransferase CBP constitutes a novel mechanism ensures We found COASY knockdown triggers prolonged mitosis multinucleation. Acetylome analysis reveals inactivation leads hyper-acetylation proteins associated with mitosis, including an Aurora kinase activator, TPX2. During early transient...