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Benjamin Miller

TitleProfessor
InstitutionSchool of Medicine and Dentistry
DepartmentDermatology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 697
Rochester NY 14642
Other Positions
TitleProfessor
InstitutionSchool of Medicine and Dentistry
DepartmentBiochemistry and Biophysics

 
 Awards And Honors
1991 - 1993W. R. Grace Graduate Fellow Award  | W. R. Grace Corporation
1994 - 1996NIH Postdoctoral Fellowship  | NIH
1998 - 2000Research Corporation Research Innovation Award  | Research Corporation
2001 - 2006Camille Dreyfus Teacher-Scholar Award  | Dreyfus Foundation
2009     Rochester Business Journal Health Care Achievement Award  | Rochester Business Journal
 
 Overview
Research in the Miller group focuses on two fundamental areas: the control of biomolecular interactions through the synthesis of new small-molecule probes, and the observation of biomolecular interactions through the development of novel optical sensing technologies. In the area of control, we are particularly interested in the sequence-selective recognition of RNA. New RNA sequences with important functions in basic biology and human health and disease are being discovered at an ever-increasing rate, and yet our ability to target these sequences specifically is still at a rudimentary stage. To address this gap, we are applying techniques of molecular design and a novel combinatorial method of small-molecule evolution called Dynamic Combinatorial Chemistry, which allows us to rapidly "prototype" sequence-selective RNA binding molecules. Thus far we have used this methodology to RNA targets important in Myotonic Dystrophy and HIV. Protein-targeted small-molecule discovery projects are also of interest, and current projects include the mechanism of tight junction formation and the transport of beta-amyloid across the blood-brain barrier. To the end of achieving better methods of observing biomolecular interactions, our group has a longstanding program in the use of the optical properties of nanostructured materials as the basis for new biosensors and diagnostic tools. Two examples of current efforts include Arrayed Imaging Reflectometry (AIR) and sensors based on two-dimensional photonic crystals (2-D PhC). AIR relies on the creation of a near-perfect antireflection coating on the surface of a silicon chip; binding of a biomolecular target destroys this antireflective condition and is visible by a change in reflected light. This allows for highly multiplexed (10's to 1000's of targets) and quantitative detection. Photonic crystal sensors, on the other hand, offer the possibility of ultrasensitive detection: for example, a major long-term goal of our work is the production of sensors that can effectively detect one virus in a blood sample.

 
 Selected Publications
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  1. Ofori LO, Hilimire TA, Bennett RP, Brown NW, Smith HC, Miller BL. High-Affinity Recognition of HIV-1 Frameshift-Stimulating RNA Alters Frameshifting in Vitro and Interferes with HIV-1 Infectivity. J Med Chem. 2014 Feb 13; 57(3):723-32.
    View in: PubMed
  2. Yadav AR, Mace CR, Miller BL. Examining the Interactions of the Splicing Factor MBNL1 with Target RNA Sequences via a Label-Free, Multiplex Method. Anal Chem. 2014 Jan 21; 86(2):1067-75.
    View in: PubMed
  3. Lifson MA, Basu Roy D, Miller BL. Enhancing the Detection Limit of Nanoscale Biosensors via Topographically Selective Functionalization. Anal Chem. 2014 Jan 21; 86(2):1016-22.
    View in: PubMed
  4. Finn RD, Miller BL, Clements J, Bateman A. iPfam: a database of protein family and domain interactions found in the Protein Data Bank. Nucleic Acids Res. 2014 Jan 1; 42(1):D364-73.
    View in: PubMed
  5. Yadav AR, Sriram R, Carter JA, Miller BL. Comparative study of solution-phase and vapor-phase deposition of aminosilanes on silicon dioxide surfaces. Mater Sci Eng C Mater Biol Appl. 2014 Feb 1; 35:283-90.
    View in: PubMed
  6. Pal S, Yadav AR, Lifson MA, Baker JE, Fauchet PM, Miller BL. Selective virus detection in complex sample matrices with photonic crystal optical cavities. Biosens Bioelectron. 2013 Jun 15; 44:229-34.
    View in: PubMed
  7. Pal S, Fauchet PM, Miller BL. 1-d and 2-d photonic crystals as optical methods for amplifying biomolecular recognition. Anal Chem. 2012 Nov 6; 84(21):8900-8.
    View in: PubMed
  8. Ofori LO, Hoskins J, Nakamori M, Thornton CA, Miller BL. From dynamic combinatorial 'hit' to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy. Nucleic Acids Res. 2012 Jul; 40(13):6380-90.
    View in: PubMed
  9. Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S, Paquette N, Deane RJ, Thiyagarajan M, Zarcone T, Fritz G, Friedman AE, Miller BL, Zlokovic BV. A multimodal RAGE-specific inhibitor reduces amyloid ß-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest. 2012 Apr 2; 122(4):1377-92.
    View in: PubMed
  10. Peng HI, Strohsahl CM, Miller BL. Microfluidic nanoplasmonic-enabled device for multiplex DNA detection. Lab Chip. 2012 Mar 21; 12(6):1089-93.
    View in: PubMed
  11. Gromova AV, Ciszewski JM, Miller BL. Ternary resin-bound Dynamic Combinatorial Chemistry. Chem Commun (Camb). 2012 Feb 18; 48(15):2131-3.
    View in: PubMed
  12. Miller BL. DCC in the development of nucleic acid targeted and nucleic acid inspired structures. Top Curr Chem. 2012; 322:107-37.
    View in: PubMed
  13. Sriram R, Yadav AR, Mace CR, Miller BL. Validation of arrayed imaging reflectometry biosensor response for protein-antibody interactions: cross-correlation of theory, experiment, and complementary techniques. Anal Chem. 2011 May 15; 83(10):3750-7.
    View in: PubMed
  14. Pal S, Guillermain E, Sriram R, Miller BL, Fauchet PM. Silicon photonic crystal nanocavity-coupled waveguides for error-corrected optical biosensing. Biosens Bioelectron. 2011 Jun 15; 26(10):4024-31.
    View in: PubMed
  15. Mace CR, Topham DJ, Mosmann TR, Quataert SA, Treanor JJ, Miller BL. Label-free, arrayed sensing of immune response to influenza antigens. Talanta. 2011 Jan 15; 83(3):1000-5.
    View in: PubMed
  16. Peng HI, Miller BL. Recent advancements in optical DNA biosensors: exploiting the plasmonic effects of metal nanoparticles. Analyst. 2011 Feb 7; 136(3):436-47.
    View in: PubMed
  17. Peng HI, Krauss TD, Miller BL. Aging induced Ag nanoparticle rearrangement under ambient atmosphere and consequences for nanoparticle-enhanced DNA biosensing. Anal Chem. 2010 Oct 15; 82(20):8664-70.
    View in: PubMed
  18. Palde PB, Ofori LO, Gareiss PC, Lerea J, Miller BL. Strategies for recognition of stem-loop RNA structures by synthetic ligands: application to the HIV-1 frameshift stimulatory sequence. J Med Chem. 2010 Aug 26; 53(16):6018-27.
    View in: PubMed
  19. Miller BL. Dynamic covalent chemistry: Catalysing dynamic libraries. Nat Chem. 2010 Jun; 2(6):433-4.
    View in: PubMed
  20. McNaughton BR, Gareiss PC, Jacobs SE, Fricke AF, Scott GA, Miller BL. A potent activator of melanogenesis identified from small-molecule screening. ChemMedChem. 2009 Oct; 4(10):1583-9.
    View in: PubMed
  21. Peng HI, Strohsahl CM, Leach KE, Krauss TD, Miller BL. Label-free DNA detection on nanostructured Ag surfaces. ACS Nano. 2009 Aug 25; 3(8):2265-73.
    View in: PubMed
  22. Wender PA, Miller BL. Synthesis at the molecular frontier. Nature. 2009 Jul 9; 460(7252):197-201.
    View in: PubMed
  23. Gareiss PC, Miller BL. Ribosomal frameshifting: an emerging drug target for HIV. Curr Opin Investig Drugs. 2009 Feb; 10(2):121-8.
    View in: PubMed
  24. Miller BL. Diagnostics for a personalized medical future: extending our senses to the molecular scale. Stud Health Technol Inform. 2009; 149:297-310.
    View in: PubMed
  25. Gareiss PC, Sobczak K, McNaughton BR, Palde PB, Thornton CA, Miller BL. Dynamic combinatorial selection of molecules capable of inhibiting the (CUG) repeat RNA-MBNL1 interaction in vitro: discovery of lead compounds targeting myotonic dystrophy (DM1). J Am Chem Soc. 2008 Dec 3; 130(48):16254-61.
    View in: PubMed
  26. Mace CR, Yadav AR, Miller BL. Investigation of non-nucleophilic additives for the reduction of morphological anomalies in protein arrays. Langmuir. 2008 Nov 18; 24(22):12754-7.
    View in: PubMed
  27. Palde PB, Gareiss PC, Miller BL. Selective recognition of alkyl pyranosides in protic and aprotic solvents. J Am Chem Soc. 2008 Jul 23; 130(29):9566-73.
    View in: PubMed
  28. Mace CR, Striemer CC, Miller BL. Detection of human proteins using arrayed imaging reflectometry. Biosens Bioelectron. 2008 Oct 15; 24(2):334-7.
    View in: PubMed
  29. Ross NT, Miller BL. Characterization of the binding surface of the translocated intimin receptor, an essential protein for EPEC and EHEC cell adhesion. Protein Sci. 2007 Dec; 16(12):2677-83.
    View in: PubMed
  30. Ross NT, Mace CR, Miller BL. Biophysical analysis of the EPEC translocated intimin receptor-binding domain. Biochem Biophys Res Commun. 2007 Nov 3; 362(4):1073-8.
    View in: PubMed
  31. McNaughton BR, Gareiss PC, Miller BL. Identification of a selective small-molecule ligand for HIV-1 frameshift-inducing stem-loop RNA from an 11,325 member resin bound dynamic combinatorial library. J Am Chem Soc. 2007 Sep 19; 129(37):11306-7.
    View in: PubMed
  32. Strohsahl CM, Krauss TD, Miller BL. Identification of high-stringency DNA hairpin probes by partial gene folding. Biosens Bioelectron. 2007 Sep 30; 23(2):233-40.
    View in: PubMed
  33. Ouyang H, Delouise LA, Miller BL, Fauchet PM. Label-free quantitative detection of protein using macroporous silicon photonic bandgap biosensors. Anal Chem. 2007 Feb 15; 79(4):1502-6.
    View in: PubMed
  34. Strohsahl CM, Miller BL, Krauss TD. Preparation and use of metal surface-immobilized DNA hairpins for the detection of oligonucleotides. Nat Protoc. 2007; 2(9):2105-10.
    View in: PubMed
  35. Bucholtz KM, Gareiss PC, Tajc SG, Miller BL. Synthesis and evaluation of the first cis-cyclobutane-containing receptor for lipid A. Org Biomol Chem. 2006 Nov 7; 4(21):3973-9.
    View in: PubMed
  36. Mace CR, Striemer CC, Miller BL. Theoretical and experimental analysis of arrayed imaging reflectometry as a sensitive proteomics technique. Anal Chem. 2006 Aug 1; 78(15):5578-83.
    View in: PubMed
  37. McNaughton BR, Miller BL. Resin-bound dynamic combinatorial chemistry. Org Lett. 2006 Apr 27; 8(9):1803-6.
    View in: PubMed
  38. Tajc SG, Miller BL. A designed receptor for pH-switchable ion binding in water. J Am Chem Soc. 2006 Mar 1; 128(8):2532-3.
    View in: PubMed
  39. Cosmanescu A, Miller B, Magno T, Ahmed A, Kremenic I. Design and implementation of a wireless (Bluetooth) four channel bio-instrumentation amplifier and digital data acquisition device with user-selectable gain, frequency, and driven reference. Conf Proc IEEE Eng Med Biol Soc. 2006; 1:2053-6.
    View in: PubMed
  40. Tolbert BS, Tajc SG, Webb H, Snyder J, Nielsen JE, Miller BL, Basavappa R. The active site cysteine of ubiquitin-conjugating enzymes has a significantly elevated pKa: functional implications. Biochemistry. 2005 Dec 20; 44(50):16385-91.
    View in: PubMed
  41. Horner SR, Mace CR, Rothberg LJ, Miller BL. A proteomic biosensor for enteropathogenic E. coli. Biosens Bioelectron. 2006 Feb 15; 21(8):1659-63.
    View in: PubMed
  42. Strohsahl CM, Du H, Miller BL, Krauss TD. Towards single-spot multianalyte molecular beacon biosensors. Talanta. 2005 Sep 15; 67(3):479-85.
    View in: PubMed
  43. Du H, Strohsahl CM, Camera J, Miller BL, Krauss TD. Sensitivity and specificity of metal surface-immobilized "molecular beacon" biosensors. J Am Chem Soc. 2005 Jun 1; 127(21):7932-40.
    View in: PubMed
  44. DeLouise LA, Kou PM, Miller BL. Cross-correlation of optical microcavity biosensor response with immobilized enzyme activity. Insights into biosensor sensitivity. Anal Chem. 2005 May 15; 77(10):3222-30.
    View in: PubMed
  45. Delouise LA, Miller BL. Enzyme immobilization in porous silicon: quantitative analysis of the kinetic parameters for glutathione-S-transferases. Anal Chem. 2005 Apr 1; 77(7):1950-6.
    View in: PubMed
  46. McNaughton BR, Bucholtz KM, Camaaño-Moure A, Miller BL. Self-selection in olefin cross-metathesis: the effect of remote functionality. Org Lett. 2005 Feb 17; 7(4):733-6.
    View in: PubMed
  47. Miller BL. Interfacing biology and computing for health: the future of home diagnostics. Stud Health Technol Inform. 2005; 118:66-78.
    View in: PubMed
  48. DeLouise LA, Miller BL. Quantatitive assessment of enzyme immobilization capacity in porous silicon. Anal Chem. 2004 Dec 1; 76(23):6915-20.
    View in: PubMed
  49. Tajc SG, Tolbert BS, Basavappa R, Miller BL. Direct determination of thiol pKa by isothermal titration microcalorimetry. J Am Chem Soc. 2004 Sep 1; 126(34):10508-9.
    View in: PubMed
  50. Lu J, Strohsahl CM, Miller BL, Rothberg LJ. Reflective interferometric detection of label-free oligonucleotides. Anal Chem. 2004 Aug 1; 76(15):4416-20.
    View in: PubMed
  51. McNaughton BR, Miller BL. A mild and efficient one-step synthesis of quinolines. Org Lett. 2003 Nov 13; 5(23):4257-9.
    View in: PubMed
  52. Du H, Disney MD, Miller BL, Krauss TD. Hybridization-based unquenching of DNA hairpins on au surfaces: prototypical "molecular beacon" biosensors. J Am Chem Soc. 2003 Apr 9; 125(14):4012-3.
    View in: PubMed
  53. Chan S, Horner SR, Fauchet PM, Miller BL. Identification of Gram negative bacteria using nanoscale silicon microcavities. J Am Chem Soc. 2001 Nov 28; 123(47):11797-8.
    View in: PubMed
  54. Karan C, Miller BL. RNA-selective coordination complexes identified via dynamic combinatorial chemistry. J Am Chem Soc. 2001 Aug 1; 123(30):7455-6.
    View in: PubMed
  55. Hubbard RD, Horner SR, Miller BL. Highly substituted ter-cyclopentanes as receptors for lipid A. J Am Chem Soc. 2001 Jun 20; 123(24):5810-1.
    View in: PubMed
  56. Hari A, Karan C, Rodrigues WC, Miller BL. Extending the scope of chromium-manganese redox-coupled reactions: a one-pot synthesis of benzoxazoles. J Org Chem. 2001 Feb 9; 66(3):991-6.
    View in: PubMed
  57. Klekota B, Miller BL. Dynamic diversity and small-molecule evolution: a new paradigm for ligand identification. Trends Biotechnol. 1999 May; 17(5):205-9.
    View in: PubMed
  58. Miller BL, Bonner WA. Enantioselective autocatalysis. III. Configurational and conformational studies on a 1,4-benzodiazepinooxazole derivative. Orig Life Evol Biosph. 1995 Dec; 25(6):539-47.
    View in: PubMed
  59. Wender PA, Irie K, Miller BL. Identification, activity, and structural studies of peptides incorporating the phorbol ester-binding domain of protein kinase C. Proc Natl Acad Sci U S A. 1995 Jan 3; 92(1):239-43.
    View in: PubMed
  60. Wender PA, Kelly RC, Beckham S, Miller BL. Studies on DNA-cleaving agents: computer modeling analysis of the mechanism of activation and cleavage of dynemicin-oligonucleotide complexes. Proc Natl Acad Sci U S A. 1991 Oct 1; 88(19):8835-9.
    View in: PubMed
  61. Pardridge WM, Buciak JL, Yang J, Miller BL, Vinters HV. Measurement of amyloid peptide precursor of Alzheimer disease in human blood by double antibody immunoradiometric assay. Alzheimer Dis Assoc Disord. 1991; 5(1):12-24.
    View in: PubMed
  62. Schaffner KF, Snyder JV, Abramson NS, Bar-Joseph G, D'Alecy LG, Edgren E, Lave JR, Meisel A, Miller BL, Mullie A, et al. Philosophical, ethical, and legal aspects of resuscitation medicine. III. Discussion. Crit Care Med. 1988 Oct; 16(10):1069-76.
    View in: PubMed
  63. Pardridge WM, Vinters HV, Miller BL, Tourtellotte WW, Eisenberg JB, Yang J. High molecular weight Alzheimer's disease amyloid peptide immunoreactivity in human serum and CSF is an immunoglobulin G. Biochem Biophys Res Commun. 1987 May 29; 145(1):241-8.
    View in: PubMed

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