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Laurie Parker

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Title

Laurie Parker
Associate Professor

Department:

Research Lab:


Lab website

Research description

Our research program is broadly directed at assay development for post-translational modifications (PTMs), with a focus on protein phosphorylation by tyrosine kinases. Protein tyrosine kinases play key roles in disease and are particularly important in cancer: mutations in several protein tyrosine kinase genes have been identified as drivers of many tumor types and drugs targeted at inhibiting these enzymes represent ~20% (>$9 billion) of the current oncology market. We use a “decoy” substrate biosensor approach (funded initially by a K99/R00 award from the NCI) in which an artificial, optimized substrate peptide is designed to report the activity of a specific enzyme in living cells. Delivery is achieved using cell-penetrating peptides, and enzymatic modification is measured using a range of readout strategies—some that require extraction of the cell contents and some that leave the cell intact. Targeting the function of the enzyme in its intracellular environment preserves protein-protein interactions, localization, and scaffolding-dependent activation, and decoy substrates provide a snapshot of enzymatic activity that circumvents the need for pre-knowledge of every endogenous substrate site. We also develop multiplex-compatible readouts, so we can use a suite of biosensors for different enzymes in order to profile pathways. We have established our approach and laid the groundwork of a substrate development workflow to expand our repertoire of biosensors for kinases and other enzymes. Long term, our lab will maintain a pipeline of biosensor and read-out technology development while also taking an active role in studying signaling biology with our tools.


Recent publications

Pub Med

Lipchik, A.M., Perez, M., Cui, W., Parker, L.L. "Multicolored, Tb3+-Based Antibody-Free Detection of Multiple Tyrosine Kinase Activities," Analytical Chem, 87(15), 7555-7558 (2015)

Lipchik, A.M., Perez, M., Bolton, S., Dumrongprechachan, V., Ouellette, S.B., Cui, W., Parker, L.L. “KINATEST-IDTM: A pipeline to develop phosphorylation-dependent terbium-sensitizing kinase assays,” Journal of the American Chemical Society, 137(7), 2484-2494 (2015)

Cui, W., Parker, L.L. “A Time-Resolved Luminescence Biosensor Assay for Anaplastic Lymphoma Kinase (ALK) Activity,” ChemComm, 51(2), 362-365 (2015)

Gui J, Liu B, Cao G, Lipchik A.M., Perez M, Dekan Z, Mobli M, Daly N.L., Alewood P.F., Parker L.L., King G.F., Zhou Y, Jordt S.E., Nitabach M.N. “A Tarantula-Venom Peptide Antagonizes the TRPA1 Nociceptor Ion Channel by Binding to the S1-S4 Gating Domain.” Current Biology, 24, 473-483 (2014)

Hu, L., Yang, L., Lipchik, A.M., Geahlen, R.L., Parker, L.L., Tao, W.G., “A quantitative proteomics-based competition binding assay to characterize ligand-protein interactions.” Analytical Chemistry, 85, 5071-5077 (2013).

Damayanti, N, Parker, L.L.* and Irudayaraj, J.* Fluorescence lifetime imaging of biosensor peptide phosphorylation in single live cells. Angewandte Chemie, Int. Ed. Eng. 52, 3931-3934 (2013). PMID: 23450802 *co-corresponding authors with equal contribution

Lipchik, A. M., Parker, L. L.  “Time-Resolved Luminescence Detection of Syk Kinase Activity Through Terbium Sensitization,” Analytical Chem., 85, 2582-2588. (2013). PMID: 23414415

Yang, T.Y., Eissler, C. L., Hall, M. C., Parker, L. L. “A multiple reaction monitoring (MRM) method to detect Bcr-Abl kinase activity in CML using a peptide biosensor” PLoS One, 8, e56627 (2013). PMID: 23437189

Parker, L.L.*, Loudon, G.M.* (*co-corresponding authors with equal contribution) “Case study using on-line homework in undergraduate organic chemistry: Results and student attitudes” Journal of Chemical Education, 90, 37-44 (2013). DOI: 10.2021/ed300270t

Lipchik, A.M.**, Killins, R. L.**, Geahlen, R.L., Parker. L.L. (**equal contribution) “Detection of intracellular Syk kinase activation using a novel peptide substrate,” Biochemistry, 51, 7515-7524 (2012). PMID: 22920457

Tang, J.B., Wang, J.Y., Parker, L.L. “Detection of early Abl kinase activation after ionizing radiation using a peptide biosensor,” ChemBioChem, 13, 665-673 (2012). PMID: 22334513

Martin, V.P., Wang, W.H., Lipchik, A.M., Parker, L. L., He, Y.T., Zhang, S., Zhang, Z.Y., Geahlen, R.L. “Akt2 inhibits the activation of NFAT in lymphocytes by modulating calcium release from intracellular stores,” Cellular Signaling, 24, 1064-1073 (2012) PMID: 22261254

Bremmer, S.C., Hall, H., Martinez, J.S., Eissler, C.L., Hinrichsen, T.H., Rossie, S., Parker, L.L., Hall, M.C., Charbonneau, H. “Cdc14 Phosphatases preferentially dephosphorylate a subset of cyclin-dependent kinase (Cdk) sites containing phosphoserine” J. Biol. Chem. 287, 1662-1669 (2012) PMID: 22117071

Eissler, C.L., Bremmer, S. C., Martinez, J.S., Parker, L. L., Charbonneau, H. and Hall, M.C. “A general strategy for studying multi-site protein phosphorylation using label-free selected reaction monitoring mass spectrometry.” 418, 267-275, Anal. Biochem. (2011). PMID: 21810403

Placzek, E.A., Plebanek, M.P., Lipchik, A., Kidd, S.R. and Parker, L.L. “A peptide biosensor for detecting intracellular Abl kinase activity using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,” Anal. Biochem., 397, 73-78 (2010). NIHMS ID# 151624; PMID: 19818327

Wu, D., Sylvester, J.E., Parker, L.L., Zhou, G., Kron, S.J. “Peptide reporters of kinase activity in whole cell lysates,” Biopolymers, 94, 475-486 (2010). PMID: 20593469

Parker, L.L., Engel-Hall, A., Drew, K., Steinhardt, G., Helseth, D.L., Jabon, D., McMurry, T., Angulo, D.S., and Kron, S.J. “Investigating quantitation of phosphorylation using MALDI-TOF mass spectrometry,” J. Mass Spectrom., 43, 518-527 (2008). NIHMS ID# 75782; PMID: 18064576

Parker, L.L. and Kron, S.J. “Kinase activation in circulating cells: Opportunities for diagnosis and therapeutic monitoring.” Expert Opin. Med. Diagn., 2, 33-46 (2008).

Wu, D., Mand, M.R., Veach, D.R., Parker, L.L., Clarkson, B., Kron, S.J. “A solid-phase Bcr-Abl kinase assay in 96-well hydrogel plates,” Anal. Biochem., 375, 18-26 (2008) PMID: 18194660

Parker, L.L., Kurutz, J.W., Kent, S.B., Kron, S.J. “Control of the yeast cell cycle with a photocleavable a-factor analog,” Angew. Chem. Int. Ed. Engl., 45, 6322-25 (2006). NIHMS ID# 75784; PMID: 16937420

  • Featured in Nature, Research Highlights, 443, 374 (2006) and ACS Chemical Biology, Spotlight, 9, 545 (2006)

Parker, L.L., Brueggemeier, S.B., Rhee, W.J., Wu, D., Kent, S.B., Kron, S.J. and Palecek S.P. “Photocleavable peptide hydrogel arrays for MALDI-TOF analysis of kinase activity,” Analyst., 131, 1097-1104 (2006) PMID: 17003856

Parker, L.L., Schilling, A.B., Kron, S.J., Kent, S.B. “Optimizing thiophosphorylation in the presence of competing phosphorylation with MALDI-TOF-MS detection,” J. Proteome Res., 4, 1863-66 (2005).  NIHMS ID# 75781; PMID: 16212443

Wu, D., Nair-Gill, E., Sher, D.A., Parker, L.L., Campbell, J.M., Siddiqui, M., Stock, W., Kron, S.J. “Assaying Bcr-Abl kinase activity and inhibition in whole cell extracts by phosphorylation of substrates immobilized on agarose beads,” Anal. Biochem., 347, 67-76 (2005). NIHMS ID# 75783; PMID: 16236241

Hutton, T.K. and Parker, L.L. 1-(4-Methoxyphenyl)-(2-(4’-methylbenzylthio)-ethylamine (an auxiliary for native chemical ligation), in Encyclopedia of Reagents for Organic Synthesis, ed. L. A. Paquette, Wiley, Chichester (2005). Also in Handbook of Reagents for Organic Synthesis: Reagents for Glycoside, Nucleotide, and Peptide Synthesis; and in e-EROS online: http://www.mrw.interscience.wiley.com/eros/articles/rn00570/frame.html

Parker, L.L.; Anderson, F.M.; O’ Hare, C.C.; Lacy, S.M.; Bingham, J.P., Robins, D.J. and Hartley J.A. “Synthesis of novel DNA cross-linking antitumour agents based on polyazamacrocycles,” Bioorg. Med. Chem., 13, 2389-95 (2005).

Parker, L.L., Lacy, S.M., Farrugia, L.J., Evans, C., Robins, D.J., O’Hare, C.C., Hartley, J.A., Jaffar, M., Stratford, I.J. “A novel design strategy for stable metal complexes of nitrogen mustards as bioreductive prodrugs.” J. Med. Chem., 47, 5683-89 (2004). PMID: 15509167

Parker, L.L.; Gowans, N.G.; Jones, S.W.; Robins, D.J. “A practical synthesis of linear and cyclic triamines using (2-trimethylsilyl)ethanesulfonamides (SES-amides).” Tetrahedron, 59, 10165-71 (2003).


 

Ph.D., University of Glasgow, UK, 2003
Phone Number
612-624-9066
Email Address

llparker@umn.edu

Address
7-140 MCB
420 Washington Avenue SE
Minneapolis, MN 55455