My research interests have evolved from basic neuroscience investigations on the hormonal regulation of behavior through hormone-neurotransmitter regulatory systems to a current focus on translational medicine, where my lab studies new candidate drugs for the treatment of psychiatric and neurodegenerative diseases. Our work bridges molecular biology, cell biology, medicinal chemistry, pharmacology, imaging, and behavioral neuroscience to characterize drug candidates, with a particular emphasis on modulating the vasopressin system in the brain to provide therapeutics for unmet needs.

The focus on the vasopressin system is based on its well-known involvement in circuitry that significantly influences social responses and the processing of emotional information. Our group, which collaborates with investigators at multiple institutions, has been involved in the development of clinical candidates spanning discovery, optimization, preclinical development, and successful Phase I and Phase 2 Clinical Trials with compounds that target the vasopressin 1a receptor, the major subtype found in the brain.

 A recent additional interest is in Traumatic Brain Injury (TBIs), which is the world’s largest neurological problem. There are no treatments for TBIs and we now understand that even a “mild” concussion can have significant long-term effects, including an increased risk of developing a neurogenerative disease later in life.

Guillon, C. Gary A. Koppel, Michael J. Brownstein, Michael O. Chaney, Craig F. Ferris, Shi- fang Lu , Karine M.Fabio , Marvin J. Miller, Ned D. Heindel, David C. Hunden, Robin D. G. Cooper, Stephen W. Kaldor, Jeffrey J. Skelton, Bruce A. Dressman Michael P. Clay, Mitchell I. Steinberg, Robert F. Bruns, Neal G. Simon,. (2007) Azetidinones as vasopressin V1a antagonists. J. Biorganic Med Chem.

Simon, N. G. and Ferris, C.F. (2007) Aversive emotions:  Hormonal basis of aggression.  In L. Squire, et al. (eds.) New Encyclopedia of Neuroscience, Elsevier.

Simon, N. and Lu, S (2006). Androgens and aggression. In R. Nelson (ed), Aggressive Behavior. Oxford Press, pp. 537-582.

Simon, N., Mo, Q., Hu, S., and Lu, S. (2006). Hormonal pathways regulating intermale and interfemale aggression.  Intl. Rev. Neurobiol., 73, 99-124

Ferris, C.F., Lu, S., Messenger, T., Miller, M., Koppel, G.A., Bruns, F.R., Simon, N.G. (2006) An orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior.  Pharmacol, Biochem. Behav, 83, 169-174

Mo, Q., Lu, S., Simon, N.G. (2006) Dehydroepiandrosterone and its metabolites: Differential
effects on androgen receptor trafficking and transcriptional activity.  J  ster. Biochem.     Mol. Biol., 99, 50-58

Hu, S., Kaplan, J., Adams, M., and Simon, N. (2005).  ER-beta protein expression in cynomolgus monkey and CF-1 mouse brain. J. Neurobiol., 64, 298-309.

Simon, N.G., Kaplan, J.R., Hu, S., Register, T.C., and Adams, M.R.(2004)  Increased aggressive behavior and decreased affiliative behavior in adult male monkeys after long-term consumption of diets rich in soy protein and isoflavones. Horm. Behav. 45, 278-284

Mo, Q., Lu, S., Hu, S., and Simon, N.G. (2004) DHEA and DHEA sulfate differentially regulate androgen receptor and its transcriptional activity. Mol. Brain Res., 126, 165-172.