The Horvath Lab applies structural methods and biochemistry to make discoveries in two broad areas: (1) DNA Repair and (2) Chronic Neuropathic Pain. For the DNA repair project we study the atomic resolution structure of MutY to understand how this enzyme recognizes and removes Adenine in OG:A base pairs. The search has led us to a microbial world in the mid-Atlantic Ocean called the Lost City where samples collected by our collaborator Dr. Brazelton (Biology) contain MutY-encoding genes. The Neuropathic pain project focuses on the alpha-9 nicotinic acetylcholine receptor and a molecule, RgIA, that blocks this receptor and alleviates pain in animal models. RgIA was discovered in the venom of the marine snail Conus regius by our collaborator Dr. McIntosh (Biology). Our current goal is to determine the structure of the alpha-9 receptor in complex with RgIA so as to design non-opioid pain drugs.
- Telomere end structure
- Structures of neuroreceptor antagonists from marine snails
- 1. Curtice, K. J., Leavitt, L. S., Chase, K., Raghuraman, S., Horvath, M. P., Olivera, B. M., and Teichert, R. W. (2016) Classifying neuronal subclasses of the cerebellum through constellation pharmacology, J Neurophysiol 115, 1031-1042.
- 2. Horvath, M. P., George, E. W., Tran, Q. T., Baumgardner, K., Zharov, G., Lee, S., Sharifzadeh, H., Shihab, S., Mattinson, T., Li, B., and Bernstein, P. S. (2016) Structure of the lutein-binding domain of human StARD3 at 1.74 A resolution and model of a complex with lutein, Acta Crystallogr F Struct Biol Commun 72, 609-618.
- 3. Olivera, B. M., Safavi-Hemami, H., Horvath, M. P., and Teichert, R. W. (2015) Conopeptides, marine natural products from venoms: biomedical applications and future research applications, in Marine Biomedicine: From Beach to Bedside (Baker, B. J., Ed.), pp 461-495, CRC Press, Boca Raton, FL (USA).
- 4. Olivera, B. M., Seger, J., Horvath, M. P., and Fedosov, A. E. (2015) Prey-Capture Strategies of Fish-Hunting Cone Snails: Behavior, Neurobiology and Evolution, Brain Behav Evol 86, 58-74.
- 5. Platt, R. J., Curtice, K. J., Twede, V. D., Watkins, M., Gruszczynski, P., Bulaj, G., Horvath, M. P., and Olivera, B. M. (2014) From molecular phylogeny towards differentiating pharmacology for NMDA receptor subtypes, Toxicon 81, 67-79.
- 6. Shyam, R., Gorusupudi, A., Nelson, K., Horvath, M. P., and Bernstein, P. S. (2017) RPE65 has an additional function as the lutein to meso-zeaxanthin isomerase in the vertebrate eye, Proc Natl Acad Sci U S A 114, 10882-10887.
- 7. Teichert, R. W., Olivera, B. M., McIntosh, J. M., Bulaj, G., and Horvath, M. P. (2015) The molecular diversity of conoidean venom peptides and their targets: from basic research to therapeutic applications, in Venoms to Drugs: Venom as a Source for the Development of Human Therapeutics (King, G. F., Ed.), pp 163-203, The Royal Society of Chemistry, Cambridge, UK.
- 8. Vickrey, A. I., Domyan, E. T., Horvath, M. P., and Shapiro, M. D. (2015) Convergent Evolution of Head Crests in Two Domesticated Columbids Is Associated with Different Missense Mutations in EphB2, Mol Biol Evol 32, 2657-2664.
- 9. Woods, R. D., O'Shea, V. L., Chu, A., Cao, S., Richards, J. L., Horvath, M. P., and David, S. S. (2016) Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases, Nucleic Acids Res 44, 801-810.
- Biol 3525/Chem 3525: Molecular Biology of DNA Lab
- Biol 3510/Chem 3510: Biological Chemistry I