Leighton Wan

All Publications

• Author Correction: Discovery of indole-modified aptamers for highly specific recognition of protein glycoforms. Nature communications Yoshikawa, A. M., Rangel, A., Feagin, T., Chun, E. M., Wan, L., Li, A., Moeckl, L., Wu, D., Eisenstein, M., Pitteri, S., Soh, H. T. 2022; 13 (1): 3452

  View details for DOI 10.1038/s41467-022-31223-5

  View details for PubMedID 35705534

• A system for multiplexed selection of aptamers with exquisite specificity without counterselection. Proceedings of the National Academy of Sciences of the United States of America Yoshikawa, A. M., Wan, L., Zheng, L., Eisenstein, M., Soh, H. T. 2022; 119 (12): e2119945119

  Abstract

  SignificanceAptamers have the capacity to discriminate between structurally similar small molecules. However, generating such highly specific aptamers has proven challenging using conventional processes based on counterselection against nontarget molecules. In this work, we describe a high-throughput screening platform that can characterize the specificity of millions of aptamers toward a group of structurally related molecules in a single experiment and generate exquisitely specific aptamers without any counterselection. As exemplars, we generated aptamers with high affinity and specificity toward three structurally related kynurenine metabolites using our platform. Our platform can be readily adapted to other small-molecule targets and should therefore accelerate the development of aptamer reagents with exquisite specificity.

  View details for DOI 10.1073/pnas.2119945119

  View details for PubMedID 35290115

• Discovery of indole-modified aptamers for highly specific recognition of protein glycoforms. Nature communications Yoshikawa, A. M., Rangel, A., Feagin, T., Chun, E. M., Wan, L., Li, A., Moekl, L., Wu, D., Eisenstein, M., Pitteri, S., Soh, H. T. 2021; 12 (1): 7106

  Abstract

  Glycosylation is one of the most abundant forms of post-translational modification, and can have a profound impact on a wide range of biological processes and diseases. Unfortunately, efforts to characterize the biological function of such modifications have been greatly hampered by the lack of affinity reagents that can differentiate protein glycoforms with robust affinity and specificity. In this work, we use a fluorescence-activated cell sorting (FACS)-based approach to generate and screen aptamers with indole-modified bases, which are capable of recognizing and differentiating between specific protein glycoforms. Using this approach, we were able to select base-modified aptamers that exhibit strong selectivity for specific glycoforms of two different proteins. These aptamers can discriminate between molecules that differ only in their glycan modifications, and can also be used to label glycoproteins on the surface of cultured cells. We believe our strategy should offer a generally-applicable approach for developing useful reagents for glycobiology research.

  View details for DOI 10.1038/s41467-021-26933-1

  View details for PubMedID 34876561

• ULTRASOUND CHARACTERIZATION OF BONE DEMINERALIZATION USING A SUPPORT VECTOR MACHINE ULTRASOUND IN MEDICINE AND BIOLOGY Denis, M., Wan, L., Fatemi, M., Alizad, A. 2018; 44 (3): 714–25

  Abstract

  We propose an ultrasound-guided remote measurement technique, utilizing an acoustic radiation force beam as our excitation source and a receiving hydrophone, to assess non-invasively a bone's mechanical properties. Features, such as velocity, were extracted from the acoustic pressure received from the bone surface. The typical velocity of an intact bone (3540 m/s) was higher in comparison to that of a demineralized bone (2231 m/s). According to the receiver operating characteristic curve, the optimal velocity cutoff value of ≥3096 m/s yields 80% sensitivity and 82.61% specificity between intact and demineralized bone. Utilizing a support vector machine, the hours of bone demineralization were successfully classified with maximum accuracy >80% using 18% training data. The results indicate the potential application of our proposed technique and support vector machine for monitoring bone mechanical properties.

  View details for PubMedID 29284556

  View details for PubMedCentralID PMC5801199