Bruce Melancon

Bruce Melancon


Research Assistant Professor, University of Notre Dame
Research Instructor, Vanderbilt Center for Neuroscience Drug Discovery
Drug Discovery Scientist I, Vanderbilt Center for Neuroscience Drug Discovery
Ruth L. Kirschstein NIH Postdoctoral Fellow, Vanderbilt University Medical Center
Ph.D. in Chemistry, University of Notre Dame
B.S. in Chemistry, Louisiana State University and A&M College

Selected Awards

George M. Wolf Graduate Fellowship, University of Notre Dame
Minna-James-Heineman Scholarship, Leibniz Universitat Hannover

Research Interests

Schizophrenia (SZ) is a complex brain disorder that affects more than 1% of the total adult population worldwide.  SZ is a devastating disease affecting individuals early in life and debilitating them through their productive years. The disease is characterized by three main conditions or symptoms:  positive symptoms involve hallucinations, delusions and paranoia; negative symptoms involve social withdrawal and anhedonia; and cognitive dysfunction involves lapses in attention and working memory. Although there have been significant improvements in the pharmaceutical intervention for the treatment of SZ over the past 50 years, the current atypical antipsychotics still only treat the positive symptoms associated with the disease.  In addition, due to the ancillary pharmacology associated with these drugs (inhibition of dopamine and/or serotonin receptors), there exist significant side effects that lead to poor quality of life. There remains significant research dedicated to the discovery of alternative targets and treatments. The muscarinic acetylcholine receptors (mAChRs), a member of Family A G-protein coupled receptors, are further divided into 5 subtypes, M1-M5.  M1 and M4 have the highest expression levels in the CNS. Much research has shown that targeting M4 with a positive allosteric modulator (PAM), reverses the psychotic-like symptoms in rodent pre-clinical models of SZ. The Melancon lab endeavors to identify novel small molecule M4 PAMs that are centrally penetrant, with excellent selectivity against the other muscarinic subtypes.  Our expertise is in the areas of hit-to-lead medicinal chemistry and lead-optimization of small molecule probes with in vivo efficacy in pre-clinical models of SZ
Infectious diseases that are caused by eukaryotic pathogens result in significant morbidity and mortality worldwide. Treatment of these diseases is often compromised by limited therapeutic options and/or development of resistance. Protozoan parasites of the genus Leishmania are the causative agents of a wide spectrum of human diseases that range from skin and mucous membrane lesions to lethality, the latter caused by a visceral species. Leishmaniasis is an emerging disease with an annual incidence of 2 million cases. More than 12 million people are infected in over 80 endemic countries, resulting in 80,000 deaths per year. The World Health Organization (WHO) has recently declared leishmaniasis as a category I Neglected Tropical Disease (NTD). In collaboration with the McDowell lab in the Department of Biology, The Melancon lab and the Chemical Synthesis & Drug Discovery Facility are engaged in a drug discovery program to identify new HTS hits with anti-leishmanial activity that are effective in an in vivo cutaneous leishmaniasis model.

Recent Papers

  • Ghoshal, A; Rook, J.M.; Dickerson, J.W.; Roop, G.N.; Morrison, R.D.; Jalan-Sakrikar, N.; Lamsal, A.; Noetzel, M.J.; Poslusney, M.S.; Wood, M.R.; Melancon, B.J.; Stauffer, S.R.; Xiang, Z.; Daniels, J.S.; Niswender, C.M.; Jones, C.K.; Lindsley, C.W.; Conn, P.J. "Potentiation of M-1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model." Neuropsychopharmacol. 2016, 41 (2), 598-610.
  • Halambage, U.D.; Wong, J.P.; Melancon, B.J.; Lindsley, C.W.; Aiken, C. "Microplate-Based Assay for Identifying Small Molecules That Bind a Specific Intersubunit Interface within the Assembled HIV-1 Capsid." Antimicrob. Agents Ch. 2015, 59 (9), 5190-5195.
  • Jalan-Sakrikar, N.; Field, J.R.; Klar, R.; Mattmann, M.E.; Gregory, K.J.; Zamorano, R.; Engers, D.W.; Bollinger, S.R.; Weaver, C.D.; Days, E.L.; Lewis, L.M.; Utley, T.J.; Hurtado, M.; Rigault, D.; Archer, F.; Walker, A.G.; Melancon, B.J.; Wood, M.R.; Lindsley, C.W.; Conn, P.J.; Xiang, Z.X.; Hopkins, C.R.; Niswender, C.M. "Identification of Positive Allosteric Modulators VU0155094 (ML397) and CU0422288 (ML396) Reveals New Insights into the Biology of Metabotropic Glutamate Receptor 7." ACS Chem. Neuro. 2014, 5 (12), 1221-1237.
  • Bubser, M.; Bridges, T.M.; Dencker, D.; Gould, R.W.; Grannan, M.; Noetzel, M.J.; Lamsal, A.; Niswender, C.M.; Daniels, J.S.; Poslusney, M.S.; Melancon, B.J.; Tarr, J.C.; Byers, F.W.; Wess, J.; Duggan, M.E.; Dunlop, J.; Wood, M.W.; Brandon, N.J.; Wood, M.R.; Linsdley, C.W.; Conn, P.J.; Jones, C.K. "Selective Activation of M-4 Muscarinic Acetylcholine Receptors Reverses MK-801-Induced Behavioral Impairments and Enhances Associative Learning in Rodents." ACS Chem. Neuro. 2014, 5 (10), 920-942.
  • Wen, W.D.; Young, S.E.; Duvernay, M.T.; Schulte, M.L.; Nance, K.D.; Melancon, B.J.; Engers, J.; Locuson, C.W.; Wood, M.R.; Daniels, J.S.; Wu, W.J.; Lindsley, C.W.; Hamm, H.E.; Stauffer, S.R. "Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354." Bioorg. Med. Chem. Lett. 2014, 24 (19), 4708-4713.
  • Byun, N. E.; Grannan, M.; Bubser, M.; Barry, R.L.; Thompson, A.; Rosanelli, J.; Gowrishankar, R.; Kelm, N.D.; Damon, S.; Bridges, T.M.; Melancon, B.J.; Tarr, J.C.; Brogan, J.T.; Avison, M.J.; Deutch, A.Y.; Wess, J.; Wood, M.R.; Lindsley, C.W.; Gore, J.C.; Conn, P.J.; Jones, C.K. "Antipsychotic Drug-Like Effects of the Selective M-4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator VU0152100." Neuropsychopharmacol. 2014, 39 (7), 1578-1593.

Contact Information

  • Research Assistant Professor; Managing Director of the Chemical Synthesis & Drug Discovery Facility
  • Office: 340F McCourtney
  • Phone: 574-631-4513
  • Send an email
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Primary Research Areas

Research Specialties