Preclinical Translational Services

Preclinical Translational Services

High throughput screening, compound formulation, and pharmacokinetic analysis.

Shared Facilities:

High Throughput Bioscience Center (HTBC)

• Description — Fully automated high-throughput screening (HTS) and high content screening of compound, genomic cDNA, and genomic siRNA libraries. Consultation and assistance for assay development, design, and analysis and for instrumentation training. Access to microplate based liquid handling equipment (SciClone ALH3000, Agilent Bravo and VPrep, Plate Washers, Reagent/Cells Dispensers), for plate replication, reformatting, reagent/cell dispensing and washing. Access to multi-mode microplate based detection equipment (AnalystGT, Flexstation and Tecan Infinite M1000 96-384-well plate readers) for fluorescence (FP, HTRF, FI, FLIPR, FRET), luminescence, and absorbance reads. Access to automated microplate imaging equipment with the ImageXpress Micro (epi-fluorescence, brightfield/phase contrast, environmental control options).
• Location — Center for Clinical Sciences Research (CCSR) 0133
• Questions — Contact David Solow-Cordero, PhD  , (650) 725-6002
• Website — http://htbc.stanford.edu/
• Selected References

  Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade. Hyman JM, Firestone AJ, Heine VM, Zhao Y, Ocasio CA, Han K, Sun M, Rack PG, Sinha S, Wu JJ, Solow-Cordero DE, Jiang J, Rowitch DH, Chen JK. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14132-7. Epub 2009 Aug 5.  PubMedID: 19666565; PMCID: PMC2721821.

  A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Paulsen RD, Soni DV, Wollman R, Hahn AT, Yee MC, Guan A, Hesley JA, Miller SC, Cromwell EF, Solow-Cordero DE, Meyer T, Cimprich KA. Mol Cell. 2009 Jul 31; 35 (2): 228-39.  PubMedID: 19647519; PMCID: PMC2772893.

  Targeting GLUT1 and the Warburg Effect in Renal Cell Carcinoma by Chemical Synthetic Lethality. Chan DA, Sutphin PD, Nguyen P, Turcotte S, Lai EW, Banh A, Reynolds GE, Chi JT, Wu J, Solow-Cordero DE, Bonnet M, Flanagan JU, Bouley DM, Graves EE, Denny WA, Hay MP, Giaccia AJ. Sci Transl Med. 2011 Aug 3;3(94):94ra70. PubMedID: 21813754.

Medicinal Chemistry Core

• Description — The Institute for Chemical Biology is pleased to announce that Dr. Mark Smith will join Stanford May 1st as a senior Academic Staff Researcher. Mark can help biologists and clinicians at Stanford incorporate medicinal chemistry into ongoing and/or future research endeavors including: the design and execution of small molecule syntheses relevant to a research project; co-mentoring an undergraduate, predoctoral, or postdoctoral researcher in a faculty member’s lab who aspires to use medicinal chemistry approaches in their research; and collaborating with faculty toward the development of one or more specific aim(s) in their grant proposals where medicinal chemical expertise is required.

 In the near future, the Institute will help Mark set up a rudimentary chemical laboratory, where he will be able to pursue hands-on research on behalf of his collaborators.  Currently the most effective way for faculty to make use of Mark’s expertise in furthering their research may be through co-mentoring of a student or postdoc. Alternatively, Mark can design and have custom-synthesized small molecules which can become tools for better understanding of biological systems. Mark’s collaborators will be expected to cover the relevant operating expenses, however Mark’s salary is fully covered by the Provost for the first two years of his appointment.
• Questions — Contact Mark Smith, PhD 
• Selected References

  Monofluoro and Difluoro Analogues of 4’-Azidocytidine Against Hepatitis C Virus Replication: the Discovery of 4’-Azido-2’-deoxy-2’-fluorocytidine and 4’-Azido-2’-dideoxy-2’,2’-difluorocytidine. Smith DB, Kalayanov G, Sund C, Winqvist A, Maltseva T, Leveque VJ, Rajyaguru S, Le Pogam S, Najera I, Benkestock K, Zhou XX, Kaiser AC, Maag H, Cammack N, Martin JA, Swallow S, Johansson NG, Klumpp K and Smith M. J Med Chem. 2009, 52, 2971. PubMedID: 19341305.

  Diphenyl Ether Non-Nucleoside Reverse transcriptase Inhibitors with Excellent Potency Against Resistant Mutant Viruses and Promising Pharmacokinetic Properties. Sweeney ZK, Kennedy-Smith JJ, Wu J, Arora N, Billedeau JR, Davidson JP, Fretland J, Hang JQ, Heilek GM, Harris SF, Hirschfeld, D, Inbar P, Javanbakht H, Jernelius JA, Jin Q, Li Y, Liang W, Roetz R, Sarma K, Smith M, Stefanidis S, Su G, Suh JM, Villasenor AG, Welch M, Zhang F-J, Klumpp K. Chem Med Chem, 2009 4, 88. PubMedID: 19006142.

  Discovery of triazolinone non-nucleoside inhibitors of HIV reverse transcriptase. Sweeney ZK, Acharya S, Briggs A, Dunn JP, Elworthy TR, Fretland J, Giannetti AM, Heilek G, Li Y, Kaiser AC, Martin M, Saito YD, Smith M, Suh JM, Swallow S, Wu J, Hang JQ, Zhou AS, Klumpp K. Bioorg Med Chem Lett, 2008, 18, 4348. PubMedID: 18625554.

Stanford Behavioral and Functional Neuroscience Lab (SBFNL)

• Description — Stanford behavioral and functional neuroscience laboratory (SBFNL) will provide expertise in all aspects related to the design and implementation of behavioral experiments as well as data analysis and interpretation. The core is fully equipped to accommodate a full battery of behavioral tests relevant to learning and memory, sensory gating, place/fear conditioning, motor function, nociception, and anxiety-related behaviors. We are specialized in genetic and pharmacological phenotyping in both mouse and rat. In addition the center provides expertise in an array of acute and chronic experimental models of neurodegenerative disorders such as stroke and ischemic brain injury.
• Questions — Contact Mehrdad Shamloo, PhD  , (650) 725-3152
• Website — http://sbfnl.stanford.edu/
• Selected References

  Mouse model of Timothy syndrome recapitulates triad of autistic traits. Bader PL, Faizi M, Owen SF, Tadross MR, Alfa RW, Bett GCL, Tsien RW, Rasmusson RL, Shamloo M. PNAS (2011; in press). PubMedID: 21878566; PMCID: PMC3174658.

  Identification of a central role for complement in osteoarthritis. Wang Q, Rozelle AL, Lepus CM, Scanzello CR, Larsen DM, Crish JF, Gurkan Bebek G, Ritter SY, Lindstrom TM, Hwang I, Wong HH, Leonardo Punzi L, Encarnacion A, Shamloo M, Goodman SB, Wyss-Coray T, Goldring SR, Gobezie R, Crow MK, Holer VM, Lee DM, and Robinson WH. Nature Medicine (2011; in press). PubMedID: 22057346.

  Restoration of Norepinephrine-Modulated Contextual Memory in a Mouse Model of Down Syndrome. Salehi A, Faizi M, Colas D, Valletta J, Laguna J, Takimoto-Kimura R, Kleschevnikov A, Wagner SL, Aisen P, Shamloo M and Mobley WC. Sci Transl Med 18 November 2009: Vol. 1, Issue 7, p. 7ra17.  PubMedID: 20368182.

Stanford Biomaterials and Advanced Drug Delivery Laboratory (BioADD)

• Description — Stanford Biomaterials and Advanced Drug Delivery Laboratory (bioADD) is a cutting edge research facility located at Stanford University . Today’s problems in drug design require complex answers to achieve effective delivery and treatment. The Stanford BioADD Laboratory helps to solve these problems with advanced modern technology and innovative solutions. Specializing in the creation of biomaterials and drug delivery agents, the laboratory lends its expertise toward designing drug formulations and developing smart materials for biomedical applications.
• Location — Grant Building S380
• Questions — Contact Jayakumar Rajadas, PhD  , (650) 724-7710
• Website — http://bioadd.stanford.edu/
• Selected References

  Vascular anastomosis using controlled phase transitions in poloxamer gels. Chang EI, Galvez MG, Glotzbach JP, Hamou CD, El-ftesi S, Rappleye CT, Sommer KM, Rajadas J, Abilez OJ, Fuller GG, Longaker MT, Gurtner GC. Nat Med. 2011 Aug 28;17(9):1147-52.   PubMedID: 21873986.

  Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling. Wong VW, Rustad KC, Akaishi S, Sorkin M, Glotzbach JP, Januszyk M, Nelson ER, Levi K, Paterno J, Vial IN, Kuang AA, Longaker MT, Gurtner GC. Nat Med. 2011 Dec 11;18(1):148-52. PubMedID: 22157678.

  Efficient gene delivery of primary human cells using peptide linked polyethylenimine polymer hybrid. Dey D, Inayathullah M, Lee AS, LeMieux MC, Zhang X, Wu Y, Nag D, De Almeida PE, Han L, Rajadas J, Wu JC. Biomaterials. 2011; 32(20):4647-58. PubMedID: 21477858.

Stanford University Mass Spectrometry (SUMS)

• Description — Capabilities include routine analyses such as nanoLC-MS/MS protein identification; LC-MS based amino acid analysis; mass determination of small molecules, peptides, and proteins; accurate mass determinations; LC-MS, MSn, and high-resolution MS. Custom projects encompass diverse areas of proteomics, metabolomics, metabolite identification, non-covalent interactions, and targeted quantitation; examples include characterization of post-translational modifications, identification of protein binding partners, proteomic and metabolomic profiling, and biomarker verification.
• Location — Mudd 175
• Questions — Contact Allis Chien, PhD  , (650) 723-0710
• Website — http://mass-spec.stanford.edu/
• Selected References

  Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD, Mochly-Rosen D. Science. 2008 Sep 12;321(5895):1493-5. PubMedID: 18787169; PMCID: PMC2741612.

  Neural Precursor Cell-expressed Developmentally Down-regulated Protein 4-2 (Nedd4-2) Regulation by 14-3-3 Protein Binding at Canonical Serum and Glucocorticoid Kinase 1 (SGK1) Phosphorylation Sites.  Chandran S, Li H, Dong W, Krasinska K, Adams C, Alexandrova L, Chien A, Hallows KR and Bhalla V. The Journal of Biological Chemistry. October 28, 2011; 286, (43): 37830-40. PubMedID: 21900244.

  Colonic Contribution to Uremic Solutes. Aronov PA, Luo F J-G, Plummer NS, Quan Z, Holmes S, Hostetter TH and Meyer TW. JASN. September 1, 2011; 22 (9): 1769-76. PubMedID: 21784895.

  Proteome-Wide Search Reveals Unexpected RNA-Binding Proteins in Saccharomyces cerevisiae. Tsvetanova NG, Klass DM, Salzman J, Brown PO. PLoS ONE. Sep 10, 2010; 5(9): e12671. doi:10.1371/journal.pone.0012671   PubMedID: 20844764; PMCID: PMC2937035.