James N. Herron
Associate Professor of Molecular Pharmaceutics and Adjunct Associate Professor of Biomedical Engineering
Structural Immunology, Vaccines, Biosensors
Our research program includes three different areas of investigation: (1) structure-function correlates of antigen-antibody complex formation; (2) biosensors and clinical diagnostics assays; and (3) targeted drug-delivery systems. A brief description of each of these is given below:
Structure-Function Correlates of Antigen-Antibody Complex Formation
The goal of this project is to understand antigen-antibody interactions at the molecular level. Our approach is to cross-correlate 3-dimensional structures obtained by X-ray crystallography with information obtained by other biophysical techniques such as fluorescence spectroscopy and calorimetry. By increasing our understanding of antigen-antibody interactions at the molecular level, we hope to comprehend how structural elements translate into the affinity and specificity of antigen-combining sites. Such mechanistic models should also facilitate the engineering of antibodies and related proteins for applications in clinical diagnostics, medical imaging and targeted drug delivery.
Biosensors and Clinical Diagnostics Assays
The goal of this project is to develop a new generation of clinical diagnostics assays that can be used in critical care or point-of-care settings. Our approach is based on planar waveguide biosensors that can selectively excite the fluorescence of molecules located within 100 nanometers of the surface of the waveguide. By immobilizing either antibodies or oligonucleotide probes to the surface of the waveguide, we can perform either immunoassays or nucleic acid hybridization assays with picomolar sensitivity in 5 minutes or less. Such assays are expected to replace the current generation of in vitro diagnostics (IVD) assays that are presently performed offsite in clinical chemistry laboratories.
This technology should lead to a significant improvement in the detection and treatment of cardiovascular disease, cancer and sexually transmitted diseases. It may also help address national priorities in the containment of health care costs.
Targeted Drug-Delivery Systems
Drug-delivery systems are typically used to improve the efficacy and safety of drugs that are poorly absorbed or have a low therapeutic index. This approach has been fairly successful, resulting in drug products such as sustained-release formulations, transdermal patches, liposomes and other colloidal delivery systems. Recent advances in biotechnology have enabled a whole new generation of drug delivery systems in which the drug is targeted to a specific site using a recognition moiety such as an antibody. We are developing targeted delivery systems for autoimmune diseases such as type I diabetes, systemic lupus erythematosus (SLE) and multiple sclerosis (MS). In particular, we are developing antibodies that will specifically target the B and T lymphocytes that are implicated in these diseases. In addition, we are working on non-traditional vaccines for autoimmune disease and cancer.
Christensen DA, Herron JN (2009) Optical System Design for Biosensors Based on CCD Detection. In: Biosensors and Protocols, Volume 1: Optical-Based Detectors (Rasooly A, Herold KE, eds.). Series: Methods in Molecular Biology, Vol 503. Humana Press, Totowa, NJ. pp. 239-258
Guo J, Elzinga P, Hageman M, Herron J (2008) Rapid Throughput Solubility Screening Method for BCS Class II Drugs in Animal GI Fluids and Simulated Human GI Fluids Using a 96-well Format. Journal of Pharmaceutical Science 97:1427-1442
Guo J, Elzinga P, Hageman M, Herron J (2008) Rapid Throughput Screening of Apparent Ksp values for Weakly Basic Drugs Using 96-Well Format. Journal of Pharmaceutical Science 97:2080-2090
Suhonen M, Li SK, Higuchi WI, Herron JN (2008) A Liposome Permeability Model for Stratum Corneum Lipid Bilayers Based on Commercial Lipids. Journal of Pharmaceutical Sciences 97:4278-4293
Jiskoot W, Visser AJWG, Herron JN, Sutter M (2005) Fluorescence Spectroscopy. In: Methods for Structural Analysis of Protein Pharmaceuticals (W. Jiskoot & D. Crommelin, eds.). AAPS Press, Arlington, VA, pp. 27-82
Liu Y, Bishop J, Williams L, Blair S, Herron J (2004) Biosensing Based upon Molecular Confinement in Metallic Nanocavity Arrays. Nanotechnology 15:1368-1374
Cavenaugh JS, Wang H-K, Sha J, Hansen C, Papangkorn K, Smith RS, Herron JN (2004) How Well Can an Idiotope Peptide Mimic Replace Its Parent Idiotype in a Synthetic Peptide Vaccine? Pharmaceutical Research 21:1480-1488
Terzyan S, Ramsland PA, Voss, Jr. EW, Herron JN, Edmundson AB (2004) Three-Dimensional Structures of Idiotypically Related Fabs with Intermediate and High Affinity for Fluorescein. Journal of Molecular Biology 339:1141-1151
Tolley SE, Wang H-K, Smith RS, Christensen DA, Herron JN (2003) Single Chain Polymorphism Analysis in Long QT Syndrome using Planar Waveguide Fluorescent Biosensors. Analytical Biochemistry 315:223-237
Cavenaugh JS, Wang H-K, Hansen C, Smith RS, Herron JN (2003) How well can a T cell epitope replace its parent carrier protein? A dose response study. Pharmaceutical Research 20:591-596
Herron JN, Wang H-K, Janatová V, Durtschi JD, Caldwell KD, Christensen DA, Chang I-N, Huang S-C (2003) Orientation and Activity of Immobilized Antibodies. In: Biopolymers at Interfaces, 2 nd Edition (M. Malmsten, ed.), Surfactant Science Series, Vol. 110, Marcel Dekker, New York, pp. 115-163
Wei A-P, Herron JN (2002) Bifluorophoric Molecules as Fluorescent Beacons for Antibody-Antigen Binding. Journal Molecular Recognition 15:311-320