My training is in medicinal chemistry and mechanistic enzymology. I have a broad background as well in molecular biology and biochemistry, and more recently, in protein crystallography. Part of my current interest is in dissecting the mechanistic basis for selective inhibitor binding to Hsp90 chaperones, focusing on correlating structural data from recent structures I have determined with isothermal titration calorimetry binding assay measurements. I have also led the Gewirth lab effort in understanding the basis for inhibitor binding to the Androgen receptor DNA binding domain. Both of these projects dovetail well with my overall interest in developing novel therapeutic approaches to cancers and other diseases.
The Team I Am On
I am a staff scientist in the laboratory of Dr. Dan Gewirth. In addition to my own research projects, I work closely with graduate students and technicians in the lab, providing day-to-day advice and guidance.
1. Patel PD, Yan P, Seidler PM, Patel HJ, Sun W, Yang C, Que NS, Taldone T, Finotti P, Stephani RA, Gewirth DT, Chiosis G. (2013) Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Nature Chemical Biology 9, 677-84. PMID 23995768.
2. Oney S, Nimjee SM, Layzer J, Que-Gewirth N, Ginsburg D, Becker RC, Arepally G, Sullenger BA. (2007) Antidote-controlled platelet inhibition targeting von Willebrand factor with aptamers. Oligonucleotides 17, 265-74. PMID 17854267
3. Que-Gewirth NS and Sullenger BA (2007) Gene therapy progress and prospects: RNA aptamers. Gene Ther. 14, 283-91. PMID 17279100
2b. Oney S, Nimjee S, Layzer J, Que-Gewirth NS, Ginsburg D, Lopez JA, Becker RC, Arepally G, Sullenger BA (2007) Antidote Controlled Platelet Inhibition Targeting von Willebrand Factor with aptamers. Oligonucleotides 17, 265-74.
4. Nahori MA, Fournie-Amazouz E, Que-Gewirth NS, Balloy V, Chignard M, Raetz CR, Saint Girons I, Werts C. (2005) Differential TLR recognition of leptospiral lipid A and lipopolysaccharide in murine and human cells. J Immunol. 175, 6022- 31.
5. Que-Gewirth NL, Ribeiro AA, Kalb SR, Cotter RJ, Bulach DM, Adler B, Saint Girons, I, Werts C, Raetz CR. (2004) A methylated phosphate group and four amide-linked acyl chains in Leptospira interrogans lipid A: The membrane anchor of an unusual lipopolysaccharide that activates TLR2. J. Biol. Chem. 279, 25420-29.
6. Que-Gewirth NL, Lin S, Cotter RJ, Raetz CR. (2003) An Outer Membrane Enzyme that Generates the 2-Amino-2-deoxy-gluconate Moiety of Rhizobium leguminosarum Lipid A. J. Biol. Chem. 278, 12109-19.
7. Que-Gewirth NLS, Karbarz MJ, Kalb S, Cotter RJ, Raetz CR. (2003) Origin of the 2-Amino-2-deoxy-gluconate Unit in Rhizobium leguminosarum Lipid A: Expression Cloning of the Outer Membrane Oxidase LpxQ. J. Biol.Chem. 278, 12120-29.
8. Que NLS, Lin S, Cotter RJ, Raetz CR. (2000) Purification and mass spectrometry of six lipid A species from the bacterial endosymbiont Rhizobium etli. Demonstration of a conserved distal unit and a variable proximal portion. J. Biol. Chem. 275, 28006-16.
9. Que NLS, Ribeiro AA, Raetz CR. (2000) Two-dimensional NMR spectroscopy and structures of six lipid A species from Rhizobium etli CE3. Detection of an acyloxyacyl residue in each component and origin of the aminogluconate moiety. J. Biol. Chem. 275, 28017-28027.
10. Chen H, Agnihotri G, Guo Z, Que NLS, Chen XH, Liu H-w. (1999) Biosynthesis of Mycarose: Isolation and Characterization of Enzymes Involved in the C-2 Deoxygenation. J. Am. Chem. Soc. 121, 8124-25.
11. Chen H, Yeung S-M, Que NLS, Muller T, Schmidt RR, Liu H-w. (1999) Expression, Purification, and Characterization of TylB, an Aminotransferase Involved in the Biosynthesis of Mycaminose. J. Am. Chem. Soc. 121, 7166-67.
12. Basu SS, White KA, Que NLS, Raetz CR. (1999) A Deacylase in Rhizobium leguminosarum that Cleaves the 3-O-Linked Hydroxymyristate Moiety of Lipid A Precursors. J. Biol. Chem. 274, 11150-58.
13. Zhao, L, Que, NLS, Xue, Y, Sherman, DH, and Liu, H-w. (1998) Mechanistic studies of desosamine biosynthesis: C-4 deoxygenation precedes C-3 transamination. J. Am. Chem. Soc. 120,12159-60.
14. Garrett TA, Que NLS, Raetz CR. (1998) Accumulation of a Lipid A Precursor Lacking the 4′-Phosphate Following Inactivation of the Escherichia coli lpxK Gene.J. Biol. Chem. 273, 12457-65.
15. Hallis TM, Lei Y, Que NLS, Liu, H-w. (1998) Mechanistic Studies of the Biosynthesis of Paratose: Purification and characterization of CDP-paratose Synthase.Biochemistry 37, 4935-45.
16. Li K, Du W, Que NLS, Liu H-w. (1996) Mechanistic Studies of 1-Aminocyclo-propane-1-carboxylate Deaminase: Unique Covalent Catalysis by Coenzyme B6. J. Am. Chem. Soc. 118, 8763-64.
17. Shin I, Zhou H-q, Que NLS, Liu H-w. (1993) A Sex Pheromone Isolated from Macrocentrus grandii: Absolute Stereochemistry Determination and Implications.J. Org. Chem. 58, 2923-25.
18. Botuyan VE, Casareno RLB, Lim C, Que NLS, Compliance CYL. (1989) The Mutagenicity and Clastogenicity Potentials of Drugs. Chemistry Letters 1, 61-79.
19. Dalal K, Che M, Que NS, Sharma A, Yang R, Lallous N, Borgmann H, Ozistanbullu D, Tse R, Ban F, Li H, Tam KJ, Roshan-Moniri M, Leblanc E, Gleave ME, Gewirth DT, Dehm SM, Cherkasov A, Rennie PS. Bypassing drug-resistance mechanisms of prostate cancer with small-molecules that target androgen receptor chromatin interactions. Mol Cancer Ther. 2017 Aug 3. pii: molcanther.0259.2017.
Nanette Que, PhD
T: 716 898 8677