David R Fooshee

University of California, Irvine, Irvine, California, United States

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Publications (8)32.02 Total impact

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    ABSTRACT: Large databases of chemical reactions provide new data-mining opportunities and challenges. Key challenges result from the imperfect quality of the data and the fact that many of these reactions are not properly balanced or atom-mapped. Here, we describe ReactionMap, an efficient atom-mapping algorithm. Our approach uses a combination of maximum common chemical subgraph search and minimization of an assignment cost function derived empirically from training data. We use a set of over 259,000 balanced atom-mapped reactions from the SPRESI commercial database to train the system, and we validate it on random sets of 1000 and 17,996 reactions sampled from this pool. These large test sets represent a broad range of chemical reaction types, and ReactionMap correctly maps about 99% of the atoms and about 96% of the reactions, with a mean time per mapping of 2 s. Most correctly mapped reactions are mapped with high confidence. Mapping accuracy compares favorably with ChemAxon’s AutoMapper, versions 5 and 6.1, and the DREAM Web tool. These approaches correctly map 60.7%, 86.5%, and 90.3% of the reactions, respectively, on the same data set. A ReactionMap server is available on the ChemDB Web portal at http://cdb.ics.uci.edu.
    Journal of Chemical Information and Modeling 11/2013; 53(11):2812–2819. · 4.30 Impact Factor
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    ABSTRACT: Background: This was to identify mechanisms of innate resistance to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Specifically, we analyzed the role of HRAS mutations in erlotinib resistance. Methods: Erlotinib sensitivity was determined by MTT assays. Molecular signaling pathways and somatic mutations were examined. Changes in sensitivity after modulation of HRAS expression were evaluated. Results: All seven cell lines were wild-type for EGFR and KRAS regardless of erlotinib sensitivity; however, one erlotinib-resistant cell line (HN31) harbored an HRAS G12D mutation. Down regulation of HRAS expression by siRNA or shRNA in HN31 led to increased erlotinib sensitivity in vitro and in vivo. Transfection of activating HRAS-mutant (G12D and G12V) constructs into erlotinib-sensitive cell lines made them more resistant to erlotinib. Conclusion: Activating HRAS mutations can confer erlotinib resistance in an HRAS mutant HNSCC cell line. Head Neck, 2013.
    Head & Neck 09/2013; · 2.83 Impact Factor
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    ABSTRACT: Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to their complex and dynamic chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions in OA formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next. The simulation generated thousands of structures in the mass range of 120-500 Da and correctly predicted ∼70% of the individual OA constituents observed by high-resolution mass spectrometry. Select predicted structures were confirmed with tandem mass spectrometry. Esterification was shown to play the most significant role in oligomer formation, with hemiacetal formation less important, and aldol condensation insignificant. COBRA is not limited to atmospheric aerosol chemistry; it should be applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods.
    Environmental Science & Technology 05/2012; 46(11):6048-55. · 5.48 Impact Factor
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    ABSTRACT: We investigated the effects of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2) and epidermal growth factor receptor (EGFR), alone and in combination with paclitaxel in an orthotopic mouse model of human head and neck squamous cell carcinoma (HNSCC). The in vitro effects of vandetanib (ZACTIMA) were assessed in 2 HNSCC cell lines on cell growth, apoptosis, receptor and downstream signaling molecule expression, and phosphorylation levels. We assessed in vivo effects of vandetanib and/or paclitaxel by measuring tumor cell apoptosis, endothelial cell apoptosis, microvessel density, tumor size, and animal survival. In vitro, vandetanib inhibited the phosphorylation of EGFR and its downstream targets in HNSCC cells and inhibited proliferation and induced apoptosis of HNSCC cells and extended survival and inhibited tumor growth in nude mice orthotopically injected with human HNSCC. Vandetanib has the potential to be a novel molecular targeted therapy for HNSCC.
    Head & Neck 03/2011; 33(3):349-58. · 2.83 Impact Factor
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    ABSTRACT: Anaplastic thyroid cancer (ATC) is a locally aggressive type of thyroid tumor with high rate of distant metastases. With conventional treatment, the median survival ranges from 4 to 12 months; therefore, new treatment options are needed. AZD2171 is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptors (VEGFR) VEGFR-1, VEGFR-2, and VEGFR-3. The objective of the study is to determine whether AZD2171 can inhibit VEGFR-2 signaling and decrease tumor growth and prolong survival of ATC in an orthotopic nude mouse model. We examined the effects of AZD2171 on phosphorylation of VEGFR-2, mitogen-activated protein kinase, and AKT in human umbilical vascular endothelial cells. To determine the antiproliferative and antiapoptotic effects of AZD2171, we did 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays, respectively. We assessed the antitumor effects of AZD2171 in a xenograft model of ATC using control, AZD2171, paclitaxel, and combination groups by measuring tumor size and survival. Treatment with AZD2171 led to dose-dependent inhibition of VEGFR-2 phosphorylation and its downstream signaling in human umbilical vascular endothelial cells (IC(50) for cell proliferation, 500 nmol/L). In the ATC cell lines DRO and ARO, IC(50) was 7.5 micromol/L. AZD2171 induced apoptosis in 50% of endothelial and ATC cells at 3 and 10 micromol/L concentrations, respectively. In vivo, AZD2171 led to a significant reduction in tumor size between control and AZD2171 (P = 0.002) or AZD2171 + paclitaxel group (P = 0.002) but not the paclitaxel alone group (P = 0.11). Survival was significantly higher among AZD2171 (P < 0.001) and combination groups (P < 0.001) compared with control. AZD2171 effectively inhibits tumor growth and prolongs survival of ATC-bearing mice. The main effect of AZD2171 is mediated through angiogenesis inhibition.
    Clinical Cancer Research 08/2007; 13(15 Pt 1):4519-27. · 7.84 Impact Factor
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    ABSTRACT: The existing commercial software often inadequately determines respiratory peaks for patients in respiration correlated computed tomography. A semi-automatic method was developed for peak and valley detection in free-breathing respiratory waveforms. First the waveform is separated into breath cycles by identifying intercepts of a moving average curve with the inspiration and expiration branches of the waveform. Peaks and valleys were then defined, respectively, as the maximum and minimum between pairs of alternating inspiration and expiration intercepts. Finally, automatic corrections and manual user interventions were employed. On average for each of the 20 patients, 99% of 307 peaks and valleys were automatically detected in 2.8 s. This method was robust for bellows waveforms with large variations.
    Medical Physics 11/2006; 33(10):3634-6. · 2.91 Impact Factor
  • Medical Physics 01/2006; 33(6). · 2.91 Impact Factor
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    ABSTRACT: An important consideration in four-dimensional CT scanning is the selection of a breathing metric for sorting the CT data and modeling internal motion. This study compared two noninvasive breathing metrics, spirometry and abdominal height, against internal air content, used as a surrogate for internal motion. Both metrics were shown to be accurate, but the spirometry showed a stronger and more reproducible relationship than the abdominal height in the lung. The abdominal height was known to be affected by sensor placement and patient positioning while the spirometer exhibited signal drift. By combining these two, a normalization of the drift-free metric to tidal volume may be generated and the overall metric precision may be improved.
    Medical Physics 08/2005; 32(7):2351-7. · 2.91 Impact Factor

Publication Stats

82 Citations
32.02 Total Impact Points

Institutions

  • 2012–2013
    • University of California, Irvine
      • • Institute for Genomics and Bioinformatics
      • • Department of Chemistry
      Irvine, California, United States
  • 2007–2013
    • University of Texas MD Anderson Cancer Center
      • Department of Head and Neck Surgery
      Houston, Texas, United States