Research Topics
Genomes and Genes
| Jeffrey W SmithSummaryAffiliation: The Burnham Institute Country: USA Publications
Research Grants
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Detail Information
Publications
Cilengitide MerckJeffrey W Smith
Burnham Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037 1005, USA
Curr Opin Investig Drugs 4:741-5. 2003..These were ongoing in February 2002, by which time, a phase I trial and a phase I/II trial in glioblastoma were underway...- Selection and structure of ion-selective ligands for platelet integrin alpha IIb(beta) 3Jeffrey W Smith
Program on Cell Adhesion, Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 277:10298-305. 2002..All peptides formed turns, with the RGD motif at the apex. The Mg(2+)-selected peptides contained a unique basic patch that protrudes from the base of the turn... 
Fabrication of PLGA nanoparticles with a fluidic nanoprecipitation systemHui Xie
Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 USA
J Nanobiotechnology 8:18. 2010..We developed a novel Fluidic NanoPrecipitation System (FNPS) to fabricate highly uniform PLGA particles. Several parameters can be fine-tuned to generate particles of various sizes...- The two-component NS2B-NS3 proteinase represses DNA unwinding activity of the West Nile virus NS3 helicaseAndrei V Chernov
Burnham Institute for Medical Research, La Jolla, California 92037, USA
J Biol Chem 283:17270-8. 2008.... - Switching the substrate specificity of the two-component NS2B-NS3 flavivirus proteinase by structure-based mutagenesisSergey A Shiryaev
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA, USA
J Virol 81:4501-9. 2007.... 
Structure-based mutagenesis identifies important novel determinants of the NS2B cofactor of the West Nile virus two-component NS2B-NS3 proteinaseIlian Radichev
Inflammatory and Infectious Disease Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
J Gen Virol 89:636-41. 2008..Because of the significant level of homology in flaviviral NS2B-NS3pro, our results will be useful for the development of specific allosteric inhibitors designed to interfere with the productive interactions of NS2B with NS3pro...- Proteolysis of the membrane type-1 matrix metalloproteinase prodomain: implications for a two-step proteolytic processing and activationVladislav S Golubkov
Burnham Institute for Medical Research, La Jolla, California 92037, USA
J Biol Chem 282:36283-91. 2007..These findings shed more light on the functional role of the inhibitory prodomain and on the proteolytic control of MT1-MMP activation, a crucial process that may be differentially regulated in normal and cancer cells... - Substrate cleavage analysis of furin and related proprotein convertases. A comparative studyAlbert G Remacle
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
J Biol Chem 283:20897-906. 2008..Our results also suggest that pathogens, including anthrax PA83 and the avian influenza A H5N1 (bird flu) hemagglutinin precursor, evolved to be as sensitive to PC proteolysis as the most sensitive normal human proteins... - Expression and purification of a two-component flaviviral proteinase resistant to autocleavage at the NS2B-NS3 junction regionSergey A Shiryaev
Inflammatory and Infectious Disease Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Protein Expr Purif 52:334-9. 2007..This construct exhibits high stability and functional activity and is thus well suited for the follow-up purification and structural and drug design studies... - Cleavage preference distinguishes the two-component NS2B-NS3 serine proteinases of Dengue and West Nile virusesSergey A Shiryaev
Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Biochem J 401:743-52. 2007..We believe that our data represent a valuable biochemical resource and a solid foundation to support the design of selective substrates and synthetic inhibitors of flaviviral proteinases... - Unusual binding of ursodeoxycholic acid to ileal bile acid binding protein: role in activation of FXRαChangming Fang
Cancer Research Center, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
J Lipid Res 53:664-73. 2012..Furthermore, IBABP is necessary for the full activation of farnesoid X receptor α (FXRα) by bile acids, including UDCA. These observations suggest that IBABP may have a role in mediating some of the intestinal effects of UDCA... - Genome-wide changes accompanying knockdown of fatty acid synthase in breast cancerLynn M Knowles
Cancer Research Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
BMC Genomics 8:168. 2007..Inhibition of tumor FAS causes both cell cycle arrest and apoptosis, indicating FAS is a promising target for cancer treatment... - Synthesis of novel beta-lactone inhibitors of fatty acid synthaseRobyn D Richardson
NCI Cancer Center, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 51:5285-96. 2008..These findings support the idea that an orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development... - Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4Lynn M Knowles
Cancer Research Center, Burham Institute for Medical Research, La Jolla, California 92037, USA
J Biol Chem 283:31378-84. 2008..These findings indicate that suppression of palmitate synthesis is not sufficient for eliciting tumor cell death and suggest that the unique effect of inhibition of FAS results from negative regulation of the mTOR pathway via DDIT4... - Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogensSergey A Shiryaev
Burnham Institute for Medical Research, La Jolla, California 92037, USA
J Biol Chem 282:20847-53. 2007..Our results confirm that inhibiting furin-like PCs protects the host from the distinct furin-dependent infections and lay a foundation for novel, host cell-focused therapies against acute diseases... - Competitive interactions of collagen and a jararhagin-derived disintegrin peptide with the integrin alpha2-I domainLester J Lambert
Burnham Institute for Medical Research, La Jolla, California 92037, USA
J Biol Chem 283:16665-72. 2008.... - Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphorylationValentina Fogal
Cancer Research Center, Burnham Institute for Medical Research, 10901 N Torrey Pines Rd, La Jolla, California 92037, USA
Mol Cell Biol 30:1303-18. 2010.... - Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for lipogenesis in hypoxic melanoma cellsFabian V Filipp
Sanford Burnham Medical Research Institute, Cancer Research Center, La Jolla, CA, USA
Pigment Cell Melanoma Res 25:375-83. 2012..This reductive carboxylation is catalyzed by two isocitrate dehydrogenases, IDH1 and IDH2. Their combined action is necessary and sufficient to effect the reverse TCA flux and maintain cellular viability... - Cleavage targets and the D-arginine-based inhibitors of the West Nile virus NS3 processing proteinaseSergey A Shiryaev
The Burnham Institute, La Jolla, CA 92037, USA
Biochem J 393:503-11. 2006..Overall, our findings represent a foundation for in-depth mechanistic and structural studies as well as for the design of novel and efficient inhibitors of WNV NS3... - Crystal and solution structures of a prokaryotic M16B peptidase: an open and shut caseAlexander E Aleshin
Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Structure 17:1465-75. 2009..Moreover, clam-shell closure is required for proteolytic activity. We predict that other prokaryotic M16B family members will form dimeric peptidasomes, and propose a model for the evolution of the M16 family... - Inflammatory proprotein convertase-matrix metalloproteinase proteolytic pathway in antigen-presenting cells as a step to autoimmune multiple sclerosisSergey A Shiryaev
Burnham Institute for Medical Research, La Jolla, California 92037, USA
J Biol Chem 284:30615-26. 2009..These data suggest that MMP-25 plays an important role in MS pathology and that MMP-25, especially because of its restricted cell/tissue expression pattern and cell surface/lipid raft localization, is a promising drug target in MS... - Structural determinants of limited proteolysisMarat D Kazanov
Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
J Proteome Res 10:3642-51. 2011..Overall, this study provided a foundation for accurate automated prediction of segments of protein structure susceptible to proteolytic processing and, potentially, other post-translational modifications... - Proteins and an inflammatory network expressed in colon tumorsWenhong Zhu
Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, California 92037, United States
J Proteome Res 10:2129-39. 2011..0056). This study provides new insights into the proteins and networks that are likely to drive the onset and progression of colon cancer... - Central carbon metabolism in the progression of mammary carcinomaAdam D Richardson
The Cancer Center, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Breast Cancer Res Treat 110:297-307. 2008..This work provides the first comprehensive view of changes to central metabolism as a result of breast tumor progression... - PMAP: databases for analyzing proteolytic events and pathwaysYoshinobu Igarashi
The Center on Proteolytic Pathways, The Cancer Research Center and The Inflammatory and Infectious Disease Center, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Nucleic Acids Res 37:D611-8. 2009..Here, we describe how the databases of PMAP can be used to foster understanding of proteolytic pathways, and equally as significant, to reason about proteolysis... - Functional specialization in proline biosynthesis of melanomaJessica De Ingeniis
Sanford Burnham Medical Research Institute, La Jolla, California, United States of America
PLoS ONE 7:e45190. 2012..PYCRL, localized in the cytosol, is exclusively linked to the conversion of ornithine to proline. This analysis provides the first clarification of the role of PYCRs to proline biosynthesis... - A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2Lynn M Knowles
Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 279:30540-5. 2004..Altogether, the findings of the study reveal unappreciated links between fatty acid synthase and ubiquitin-dependent proteolysis of cell-cycle regulatory proteins... - Glutamine-fueled mitochondrial metabolism is decoupled from glycolysis in melanomaFabian V Filipp
Cancer Research Center, Sanford Burnham Medical Research Institute, La Jolla, CA, USA
Pigment Cell Melanoma Res 25:732-9. 2012..Biosynthetic networks linked with non-essential amino acids alanine, serine, arginine, and proline are also significantly impacted by the use of glutamine as an alternate carbon source... - A residue in the S2 subsite controls substrate selectivity of matrix metalloproteinase-2 and matrix metalloproteinase-9Emily I Chen
Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA
J Biol Chem 278:17158-63. 2003..The residues that occupy this position in other MMPs are highly variable, providing a potential structural basis for substrate recognition across the MMP family... - Redox control of integrin adhesion receptorsJeffrey W Smith
Cancer Research Center, Burnham Institute, La Jolla, California 92037, USA
Methods Enzymol 353:156-63. 2002 - Maspin alters the carcinoma proteomeEmily I Chen
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
FASEB J 19:1123-4. 2005..These observations reveal for the first time the far reaching effects of maspin on multiple protein networks and a new hypothesis of maspin function based on the regulation of proteasome function... - One-step fabrication of polymeric Janus nanoparticles for drug deliveryHui Xie
The Sanford Burnham Medical Research Institute, La Jolla, California 92037, United States
Langmuir 28:4459-63. 2012..To the best of our knowledge, this is the first demonstration of biocompatible Janus nanoparticles that encapsulate a hydrophobic drug (paclitaxel) on one side and a hydrophilic drug (doxorubicin hydrochloride) on the other... - Methods for analysis of the integrin ligand binding eventJeffrey W Smith
Burnham Institute, La Jolla, California 92037, USA
Methods Cell Biol 69:247-59. 2002 - High throughput substrate phage display for protease profilingBoris Ratnikov
Center on Proteolytic Pathways, Burnham Institute for Medical Research, La Jolla, CA, USA
Methods Mol Biol 539:93-114. 2009..The semiautomated platform allows one to obtain an order of magnitude more data, thus permitting precise comparisons among related proteases to define their functional distinctions... - Novel antagonists of the thioesterase domain of human fatty acid synthaseRobyn D Richardson
Cancer Research Center and Center on Proteolytic Pathways, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Cancer Ther 6:2120-6. 2007..This set of novel FAS antagonists provides an important pharmacologic lead for further development of anticancer therapeutics... - Comparative metabolic flux profiling of melanoma cell lines: beyond the Warburg effectDavid A Scott
Cancer Research Center, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
J Biol Chem 286:42626-34. 2011..Altogether, this study, which is the first comprehensive comparative analysis of metabolism in melanoma cells, provides a foundation for targeting metabolism for therapeutic benefit in melanoma... - A unique substrate binding mode discriminates membrane type-1 matrix metalloproteinase from other matrix metalloproteinasesSteven J Kridel
Program on Cell Adhesion, The Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 277:23788-93. 2002..Altogether the study provides a structural basis for selective and non-selective substrate recognition by MT1-MMP. The findings in this report are likely to explain several aspects of MT1-MMP biology... - Polymer particle shape independently influences binding and internalization by macrophagesGaurav Sharma
Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
J Control Release 147:408-12. 2010..The results of the study also give mechanistic guidance on how particle shape can be manipulated to design drug carriers to evade macrophages, or alternatively to target macrophages... - S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell deathZezong Gu
Center for Neuroscience and Aging, Program in Cell Adhesion and Extracellular Matrix Biology, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 297:1186-90. 2002..These findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity... - Profiling constitutive proteolytic events in vivoJohn C Timmer
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Biochem J 407:41-8. 2007..Taken together, our results demonstrate how to rapidly distinguish real proteolysis that occurs in vivo from the predictions based on in vitro experiments... - Inhibition of endothelial cell proliferation and angiogenesis by orlistat, a fatty acid synthase inhibitorCecille D Browne
Cancer Research Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
FASEB J 20:2027-35. 2006..Thus, orlistat is an antiangiogenic agent with a novel mechanism of action... - Orlistat is a novel inhibitor of fatty acid synthase with antitumor activitySteven J Kridel
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Cancer Res 64:2070-5. 2004..By virtue of its ability to inhibit fatty acid synthase, Orlistat halts tumor cell proliferation, induces tumor cell apoptosis, and inhibits the growth of PC-3 tumors in nude mice... - CutDB: a proteolytic event databaseYoshinobu Igarashi
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Nucleic Acids Res 35:D546-9. 2007..CutDB is publicly available at http://cutdb.burnham.org... - A novel variant of ileal bile acid binding protein is up-regulated through nuclear factor-kappaB activation in colorectal adenocarcinomaChangming Fang
Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
Cancer Res 67:9039-46. 2007..Collectively, the studies point toward a unique bile acid response pathway involving NF-kappaB and IBABP-L that could be useful for diagnosis and could potentially be targeted for therapeutic benefit... - An alternative processing of integrin alpha(v) subunit in tumor cells by membrane type-1 matrix metalloproteinaseBoris I Ratnikov
Burnham Institute, 10901 N Torrey Pines Road, La Jolla, California 92037, USA
J Biol Chem 277:7377-85. 2002.... - Efficient synthetic inhibitors of anthrax lethal factorMartino Forino
Burnham Institute, Cancer Research Center and Infectious and Inflammatory Disease Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 102:9499-504. 2005..Our data strongly indicate that the scaffold of inhibitors we have identified is the foundation for the development of novel, safe, and effective emergency therapy of postexposure inhalation anthrax... - Mass spectrometry-based label-free quantitative proteomicsWenhong Zhu
Center on Proteolytic Pathways, Burnham Institute for Medical Research, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
J Biomed Biotechnol 2010:840518. 2010..In this paper, we will discuss the technologies of these label-free quantitative methods, statistics, available computational software, and their applications in complex proteomics studies... - Gene expression profiling of tumor xenografts: In vivo analysis of organ-specific metastasisHyerim Lee
The Cancer Research Center, Program on Cell Adhesion at The Burnham Institute, La Jolla, CA 92037, USA
Int J Cancer 107:528-34. 2003..This raises the hypothesis that tumors preferentially metastasize to lymph nodes by using CD73 to mimic part of the lymphocyte homing process... - Beta-lactam congeners of orlistat as inhibitors of fatty acid synthaseWei Zhang
Department of Chemistry, Texas A and M University, College Station, TX 77842 3012, USA
Bioorg Med Chem Lett 18:2491-4. 2008..While in general these derivatives showed lower potency compared to beta-lactones, a reasonably potent, lead compound (-)-9 (IC(50)=8.6microM) was discovered that suggests that this class of compounds should be evaluated further... - Total synthesis and comparative analysis of orlistat, valilactone, and a transposed orlistat derivative: Inhibitors of fatty acid synthaseGil Ma
Department of Chemistry, Texas A and M University, College Station, Texas 77842-3012, USA
Org Lett 8:4497-500. 2006..Comparative antagonistic activity of these derivatives toward a recombinant form of the thioesterase domain of fatty acid synthase is reported along with comparative activity-based profiling... - Practical, catalytic, asymmetric synthesis of beta-lactones via a sequential ketene dimerization/hydrogenation process: inhibitors of the thioesterase domain of fatty acid synthaseVikram C Purohit
Department of Chemistry, Texas A and M University, P.O. Box 30012, College Station, Texas 77842-3012, USA
J Org Chem 71:4549-58. 2006..28 +/- 0.06 microM). In addition, mechanistic studies of the ketene dimerization process by ReactionView infrared spectroscopy support previous findings that ketene formation is rate determining... - HTS identifies novel and specific uncompetitive inhibitors of the two-component NS2B-NS3 proteinase of West Nile virusPaul A Johnston
Pittsburgh Molecular Library Screening Center, Department of Pharmacology, University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA
Assay Drug Dev Technol 5:737-50. 2007..We also provide the structural basis for additional species-selective allosteric inhibitors of flaviviruses... - HypercalcemiaMichelle M Shepard
Department of Internal Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
Am J Med Sci 334:381-5. 2007..Calcium stores, serum measurement, and regulation are reviewed as an introduction to understanding the etiology and treatment of hypercalcemia...
Research Grants
- A Variant of Ileal Bile Acid Binding Protein in Colon CancerJeffrey Smith; Fiscal Year: 2006....
- Vascular Integrins and Nitric OxideJeffrey Smith; Fiscal Year: 2007..abstract_text> ..
- Metalloproteinases in Tumor Progression and MetastasisJeffrey Smith; Fiscal Year: 2007..These chemical leads will be improved by iterative structure-based modifications and will be tested in cell-based assays and ultimately in animal models of tumor progression. ..
- Center on Proteolytic Pathways(RMI)Jeffrey Smith; Fiscal Year: 2007..An Outreach component is planned to ensure that the CPP achieves high visibility, and ultimately numerous connections, with the scientific research community. ..
- Nanotherapy for Vulnerable PlaqueJeffrey Smith; Fiscal Year: 2007..abstract_text> ..
- Metalloproteinases in Tumor Progression and MetastasisJeffrey Smith; Fiscal Year: 2009..These chemical leads will be improved by iterative structure-based modifications and will be tested in cell-based assays and ultimately in animal models of tumor progression. ..
- FXR signaling pathway is a valid target for chemoprevention in colorectal cancerJeffrey Smith; Fiscal Year: 2009..Results from this study are likely to provide new methods for chemoprevention, and novel assays for identifying responsive sub-populations. ..
- Applied Biosystems QStar Pulsar I with oMALDI SourceJeffrey Smith; Fiscal Year: 2003..The acquisition of the Q-Star instrument will enhance the Burnham Institute's broad, long-term effort of supporting and enabling world-class science at the interface of biology and mass spectrometry. ..
- ALPHA V INTEGRINS IN BREAST CANCERJeffrey Smith; Fiscal Year: 2002..Results from these analyses will greatly augment the interpretation of results obtained from the experiments on tumor metastasis. ..
- MECHANISM OF ACTIVATION OF PLATELET GPIIB AND GPIIIAJeffrey Smith; Fiscal Year: 2001..Binding studies will be performed between Ca2+ and purified conformers of dormant and active IIb-IIIa. Results from this analysis should determine which class of ion binding sites regulate activation of the integrin. ..
- DISINTEGRINS & METALLOPROTEINASES IN ORTHOPEDIC DISEASEJeffrey Smith; Fiscal Year: 2002..Homology-based PCR will be used to clone osteoclast ADAMs. Antibodies against these ADAMs will be used in attempts to block osteoclast differentiation. ..