Luke H. Bradley | Molecular & Cellular Biochemistry

Luke H. Bradley

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lhbradley@uky.edu
859-323-1826
MN 214 Medical Sciences Bldg
https://lhbradley1.wixsite.com/bradleylab

Position(s):

Regular Faculty

Affiliation(s):

Neuroscience

Bio / Education:

BS, Chemistry/Biochemistry, Ohio University
Ph.D., Biochemistry, Ohio State University
Postdoctoral Training, Chemistry/Synthetic Biology, Princeton University

Research Description:

Peptide and protein scaffolds for biotherapeutic discovery and development

Research in the Bradley laboratory utilizes approaches at the interface of chemistry, biochemistry, and neurobiology to discover and develop peptide and protein-based molecules as platforms for various medical, biotechnical, and biotherapeutic applications. We are using molecular design and screening techniques to develop molecules with desired biological activities and properties. In addition, biochemical and neurobiological characterization will contribute towards understanding the basis of the native molecule's function.

Selected Publications:

Fuqua JL, Littrell OM, Lundblad M, Turchan-Cholewo J, Abdelmoti LG, Galperin E, Bradley LH, Cass WA, Gash DM, Gerhardt GA. (2014) Dynamic Changes in the Dopamine Neuron Function after DNSP-11 Treatment: Effects in vivo and Increased ERK 1/2 Phosphorylation in vitro. Peptides 54: 1-8.

Hardy PA, Keeley D, Schorn G, Forman, E, Ai Y, Zhang Z, Bradley LH. (2013) Convection enhanced delivery of gadolinium-tagged polylysine. J Neuroscience Methods, 219: 169-175.

Littrell OM, Fuqua JF, Richardson AD, Turchan-Cholewo J, Hascup ER, Huettl P, Pomerleau F, Bradley LH, Gash DM, Gerhardt GA. (2013) A synthetic five amino acid GDNF propeptide increases dopamine neuron differentiation and neurochemical function. Neuropeptides, 47: 43-49.

Magnani R, Chaffin B, Dick E, Bricken ML, Houtz RL, Bradley LH. (2012) Utilization of a calmodulin lysine methyltransferase co-expression system for the generation of a combinatorial library of post-translationally modified proteins. Protein Expression & Purification, 86: 83-88.

Sexton T, Boock LJ, Rodgers DR, Bradley LH, Hersh LB. (2012) Active site mutations change the substrate cleavage specificity of neprilysin. PLoS ONE, 7(2): e32343.

Arai R, Kobayashi N, Kimura A, Sato T, Wang AF, Platt JM, Bradley LH, Hecht MH. (2012) Domain-swapped dimeric structure of a de novo 4-helix bundle protein, WA20. J Phys Chem B, 116: 6569-7032.

Bradley LH, Bricken ML, Randle C. (2011) Expression, purification, and characterization of proteins from high-quality combinatorial libraries of the mammalian calmodulin central linker. Protein Expression & Purification 75: 186-192.

Kelps KA, Turchan-Cholewo J, Hascup ER, Taylor TL, Gash DM, Gerhardt GA, Bradley LH. (2011) Evaluation of the physical and in vitro protective activity of three synthetic peptides derived from the pro- and mature GDNF sequence. Neuropeptides 45(3): 213-218.

Bradley LH, Fuqua J, Richardson A, Turchan-Cholewo J, Ai Y, Kelps KA, Glass J, He X, Zhang Z, Grondin R, Littrell OM, Gash DM, Gerhardt GA. (2010) Dopamine neuron stimulating actions of a GDNF propeptide. PLoS ONE 5(3): e9752.

Patel SC, Bradley LH, Jinadasa SP, Hecht MH. (2009) Cofactor Binding and Enzymatic Activity in an Unevolved Superfamily of De Novo Designed 4-Helix Bundle Proteins. Protein Science, 18:1388-1400.

Bradley LH, Thumfort PP, Hecht MH. (2006) De novo proteins from binary patterned combinatorial libraries. Methods Mol Biol 340: 53-69.

Bradley LH, Kleiner RE, Wang AF, Hecht MH, Wood DW. (2005) An Intein-Based Genetic Selection Enables Construction of a High-Quality Library of Binary Patterned De Novo Protein Sequences. Protein Engineering, Design & Selection 18: 201-207.

PubMed Publications:

Grondin, R.;Littrell, OM ;Zhang, Z.;Ai, Y.;Huettl, P.;Pomerleau, F.;Quintero, JE ;Andersen, AH ;Stenslik, MJ ;Bradley, LH ;Lemmon, J.;O'Neill, MJ ;Gash, DM ;Gerhardt, GA "GDNF revisited: A novel mammalian cell-derived variant form of GDNF increases dopamine turnover and improves brain biodistribution." Neuropharmacology (2018): [PubMed Link] | [ Full text ]
Stenslik, MJ ;Evans, A.;Pomerleau, F.;Weeks, R.;Huettl, P.;Foreman, E.;Turchan-Cholewo, J.;Andersen, A.;Cass, WA ;Zhang, Z.;Grondin, RC ;Gash, DM ;Gerhardt, GA ;Bradley, LH "Methodology and effects of repeated intranasal delivery of DNSP-11 in awake Rhesus macaques." Journal of neuroscience methods 303, (2018): 30-40. [PubMed Link] | [ Full text ]
Smit, R.;Bouwens, RJ ;Carniani, S.;Oesch, PA ;Labbé, I.;Illingworth, GD ;Werf, P.;Bradley, LD ;Gonzalez, V.;Hodge, JA ;Holwerda, BW ;Maiolino, R.;Zheng, W. "Rotation in C ii -emitting gas in two galaxies at a redshift of 6.8." Nature 553, 7687 (2018): 178-181. [PubMed Link] | [ Full text ]
Stenslik, MJ ;Potts, LF ;Sonne, JW ;Cass, WA ;Turchan-Cholewo, J.;Pomerleau, F.;Huettl, P.;Ai, Y.;Gash, DM ;Gerhardt, GA ;Bradley, LH "Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease." Journal of neuroscience methods 251, (2015): 120-9. [PubMed Link] | [ Full text ]
Fuqua, JL ;Littrell, OM ;Lundblad, M.;Turchan-Cholewo, J.;Abdelmoti, LG ;Galperin, E.;Bradley, LH ;Cass, WA ;Gash, DM ;Gerhardt, GA "Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro." Peptides 54, (2014): 1-8. [PubMed Link] | [ Full text ]
Bradley, LH "High-quality combinatorial protein libraries using the binary patterning approach." Methods in molecular biology (Clifton, N.J.) 1216, (2014): 117-28. [PubMed Link] | [ Full text ]
Hardy, PA ;Keeley, D.;Schorn, G.;Forman, E.;Ai, Y.;Venugopalan, R.;Zhang, Z.;Bradley, LH "Convection enhanced delivery of different molecular weight tracers of gadolinium-tagged polylysine." Journal of neuroscience methods 219, 1 (2013): 169-75. [PubMed Link] | [ Full text ]
Littrell, OM ;Fuqua, JL ;Richardson, AD ;Turchan-Cholewo, J.;Hascup, ER ;Huettl, P.;Pomerleau, F.;Bradley, LH ;Gash, DM ;Gerhardt, GA "A synthetic five amino acid propeptide increases dopamine neuron differentiation and neurochemical function." Neuropeptides 47, 1 (2013): 43-9. [PubMed Link] | [ Full text ]
Arai, R.;Kobayashi, N.;Kimura, A.;Sato, T.;Matsuo, K.;Wang, AF ;Platt, JM ;Bradley, LH ;Hecht, MH "Domain-swapped dimeric structure of a stable and functional de novo four-helix bundle protein, WA20." The journal of physical chemistry. B 116, 23 (2012): 6789-97. [PubMed Link] | [ Full text ]
Magnani, R.;Chaffin, B.;Dick, E.;Bricken, ML ;Houtz, RL ;Bradley, LH "Utilization of a calmodulin lysine methyltransferase co-expression system for the generation of a combinatorial library of post-translationally modified proteins." Protein expression and purification 86, 2 (2012): 83-8. [PubMed Link] | [ Full text ]
Sexton, T.;Hitchcook, LJ ;Rodgers, DW ;Bradley, LH ;Hersh, LB "Active site mutations change the cleavage specificity of neprilysin." PloS one 7, 2 (2012): e32343. [PubMed Link] | [ Full text ]
Kelps, KA ;Turchan-Cholewo, J.;Hascup, ER ;Taylor, TL ;Gash, DM ;Gerhardt, GA ;Bradley, LH "Evaluation of the physical and in vitro protective activity of three synthetic peptides derived from the pro- and mature GDNF sequence." Neuropeptides 45, 3 (2011): 213-8. [PubMed Link] | [ Full text ]
Fisher, MA ;McKinley, KL ;Bradley, LH ;Viola, SR ;Hecht, MH "De novo designed proteins from a library of artificial sequences function in Escherichia coli and enable cell growth." PloS one 6, 1 (2011): e15364. [PubMed Link] | [ Full text ]
Bradley, LH ;Bricken, ML ;Randle, C. "Expression, purification, and characterization of proteins from high-quality combinatorial libraries of the mammalian calmodulin central linker." Protein expression and purification 75, 2 (2011): 186-91. [PubMed Link] | [ Full text ]
Bradley, LH ;Fuqua, J.;Richardson, A.;Turchan-Cholewo, J.;Ai, Y.;Kelps, KA ;Glass, JD ;He, X.;Zhang, Z.;Grondin, R.;Littrell, OM ;Huettl, P.;Pomerleau, F.;Gash, DM ;Gerhardt, GA "Dopamine neuron stimulating actions of a GDNF propeptide." PloS one 5, 3 (2010): e9752. [PubMed Link] | [ Full text ]
Patel, SC ;Bradley, LH ;Jinadasa, SP ;Hecht, MH "Cofactor binding and enzymatic activity in an unevolved superfamily of de novo designed 4-helix bundle proteins." Protein science : a publication of the Protein Society 18, 7 (2009): 1388-400. [PubMed Link] | [ Full text ]
Bradley, LH ;Wei, Y.;Thumfort, P.;Wurth, C.;Hecht, MH "Protein design by binary patterning of polar and nonpolar amino acids." Methods in molecular biology (Clifton, N.J.) 352, (2007): 155-66. [PubMed Link] | [ Full text ]
Bradley, LH ;Thumfort, PP ;Hecht, MH "De novo proteins from binary-patterned combinatorial libraries." Methods in molecular biology (Clifton, N.J.) 340, (2006): 53-69. [PubMed Link] | [ Full text ]
Bradley, LH ;Kleiner, RE ;Wang, AF ;Hecht, MH ;Wood, DW "An intein-based genetic selection allows the construction of a high-quality library of binary patterned de novo protein sequences." Protein engineering, design & selection : PEDS 18, 4 (2005): 201-7. [PubMed Link] | [ Full text ]
Hecht, MH ;Das, A.;Go, A.;Bradley, LH ;Wei, Y. "De novo proteins from designed combinatorial libraries." Protein science : a publication of the Protein Society 13, 7 (2004): 1711-23. [PubMed Link] | [ Full text ]
Bradley, LH ;Swenson, RP "Role of hydrogen bonding interactions to N(3)H of the flavin mononucleotide cofactor in the modulation of the redox potentials of the Clostridium beijerinckii flavodoxin." Biochemistry 40, 30 (2001): 8686-95. [PubMed Link] | [ Full text ]
Chang, F.;Bradley, LH ;Swenson, RP "Evaluation of the hydrogen bonding interactions and their effects on the oxidation-reduction potentials for the riboflavin complex of the Desulfovibrio vulgaris flavodoxin." Biochimica et biophysica acta 1504, 2-3 (2001): 319-28. [PubMed Link] | [ Full text ]
Bradley, LH ;Swenson, RP "Role of glutamate-59 hydrogen bonded to N(3)H of the flavin mononucleotide cofactor in the modulation of the redox potentials of the Clostridium beijerinckii flavodoxin. Glutamate-59 is not responsible for the pH dependency but contributes to the..." Biochemistry 38, 38 (1999): 12377-86. [PubMed Link] | [ Full text ]
Christoff, JJ ;Bradley, L.;Miller, DD ;Lei, L.;Rodriguez, F.;Fraundorfer, P.;Romstedt, K.;Shams, G.;Feller, DR "Synthesis and evaluation of trimetoquinol derivatives: novel thromboxane A2/prostaglandin H2 antagonists with diminished beta-adrenergic agonist activity." Journal of medicinal chemistry 40, 1 (1997): 85-91. [PubMed Link] | [ Full text ]