Associate Professor
Office:  La Tourette Hall 432
Phone:  (815) 753-8654
jrhorn@niu.edu

Educational Background

Postdoctoral Fellow, University of Chicago, 2003-2006

Postdoctoral Fellow, Northwestern University Medical School, 2002-2003

Ph.D., University of Iowa, 2002

B.A., Knox College, 1996

Curriculum Vitae

Research Interests

Protein-protein and protein-small molecule interactions; molecular recognition; protein engineering; drug design.

Horn Lab Webpage

A combinatorial histidine scanning library approach to engineer highly pH-dependent protein switches. Murtaugh, M.L.; Fanning, S.W.; Sharma, T.M.; Terry, A.M.; Horn J.R. (2011) Protein Science, 20 (9):1619-1631 (Featured Cover Art).

An anti-hapten camelid antibody reveals a cryptic binding site with significant energetic contributions from a nonhypervariable loop. Fanning, S.W.; Horn, J.R. (2011) Protein Science, 20 (7): 1196–1207 (Featured Cover Art).

A Combinatorial Approach to Engineer a Dual-Specific Metal Switch Antibody. Fanning, S.W.; Murtaugh, M.; Horn, J.R. (2011) Biochemistry, 50 (23): 5093–5095.

Production and characterization of a genetically engineered anti-caffeine camelid antibody and its use in immunoaffinity chromatography. Franco, E.J.; Sonneson, G.J.; DeLegge, T.J.; Hofstetter, H.; Horn, J.R.; Hofstetter, O. (2010) J Chromatography B, 878 (2): 177-186.

Hapten-Induced Dimerization of a Single-Domain VHH Camelid Antibody. Sonneson, G. J.; Horn, J. R. (2009) Biochemistry, 48 (29): 6693–6695.

Principal determinants leading to transition state formation of a protein-protein complex, orientation trumps side chain interactions. Horn, J. R.; Sosnick, T. R.; and Kossiakoff, A. K. (2009) PNAS, 106 (8): 2559-2564.

Shotgun Alanine Scanning Shows That Growth Hormone Can Bind Productively to Its Receptor through a Drastically Minimized Interface. Kouadio, J.-L.; Horn, J. R.; Pal, G.; Kossiakoff, A. A. (2005) J. Biol. Chem., 280: 25524-25532.

Allosteric inhibition through core disruption. Horn, J. R.; Shoichet, B. K. (2004) J. Mol. Biol., 336 (5): 1283-1291.

van't Hoff and Calorimetric Enthalpies from Isothermal Titration Calorimetry: Are There Significant Discrepancies? Horn, J. R.; Russell, D.; Lewis, E. A.; Murphy, K. P. (2001) Biochemistry, 40 (6): 1774-1778.

A major constituent of biological regulation and activity involves macromolecule interactions, such as protein-protein and protein-small molecule interactions. These finely regulated interactions form the framework for maintaining cellular homeostasis. When unregulated, the results can lead to disease states (e.g., cancer, autoimmune diseases). Thus, proteins are frequently targets of therapeutic intervention.

It is of fundamental importance to understand the biophysical nature of the forces responsible for molecular recognition. Our lab addresses such questions through studying protein energetics, dynamics, and structure. We utilize both experimental and computational/theoretical approaches toward this end. The long-term goals of this research will aid in structure-based drug design and the development of novel protein engineering strategies.

To help investigate structure/energetic relationships, we use a variety of protein-protein model systems, such as the camelid antibody/antigen complex shown in Figure 1. Biophysical studies using techniques such as isothermal titration calorimetry (ITC: see the example in Figure 2), surface plasmon resonance (SPR), and X-ray crystallography combine to provide powerful insight into molecular recognition. In addition, we utilize protein engineering techniques such as phage display (molecular biology-based combinatorial chemistry) to probe and explore protein-protein interactions.

Our lab is also interested in understanding the biophysical nature of other important biological protein-protein complexes, such as those found within the bcl-2 family. These are proteins that play pivotal roles in apoptosis, the cellular death pathway.

Computational and theoretical techniques are also used to explore the nature of protein-protein and protein-small molecule interactions. For instance, molecular dynamic simulations are used to model features of protein dynamics that are often difficult to elucidate through experimental approaches. To model protein-small molecule interactions, molecular docking (virtual inhibitor discovery, Figure 3) is used to test and explore structural/energetic relationships. This technique also provides opportunities to discover novel inhibitors.

Figure 1. A camelid antibody/antigen complex.

Figure 2. Example of isothermal titration calorimetry (ITC) results.

Figure 3. Theoretical model of small-molecule docking.