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Dr. Marlene A Jacobson

Dr. Jacobson received her bachelor degree in Chemistry from Douglass College, Rutgers University and her Ph.D. in Chemistry from the University of Delaware. Upon completion of her doctoral program, Dr. Jacobson was awarded a NIH Post-Doctoral Fellowship in Chemistry at MIT and secondary appointment as Visiting Fellow in Genetics at Harvard Medical School. In 1987, she joined Merck Research Labs where, over 24 years, she pursued drug discovery and preclinical development in areas of neuroscience, including schizophrenia, Alzheimer’s disease and sleep disorders, pain and thrombosis. Dr. Jacobson is recognized for her contributions to the discovery and development of allosteric modulators of G-protein coupled receptors including muscarinic and metabotropic glutamate receptors. She has co-authored over 100 research publications, abstracts and patents. Dr. Jacobson’s research interests include neuropathic lysosomal storage disorders, molecular pharmacology of allosteric modulators and biased ligands of G-protein coupled receptors, novel screening methodologies and assay development for drug discovery.

Selected Publications

1. Williams, T, Jacobson MA, Kalinichev, M and Rocher, J-P, Activation of the mGlu5 receptor for the treatment of schizophrenia and cognitive-deficit associated disorders, Topics in Medicinal Chemistry, Special Issue on Schizophrenia (2014) Springer Berlin Heidelberg doi: 10.1007/7355_2014_57

2. Carter RL, Grisanti LA, Yu JE, Repas AA, Woodall M, Ibetti J, Koch WJ, Jacobson MA, Tilley,DG. Dynamic mass redistribution analysis of endogenous β-adrenergic receptor signaling in neonatal rat cardiac fibroblasts Pharmacol Res Perspect. 2014 Feb;2(1). doi: 10.1002/prp2.24

3. Jacobson, M.A., Kreatsoulas, C., O’Brien, J.A., Pascarella, D.M. and C. Sur,  The M1 muscarinic receptor allosteric agonist AC-42 and TBPB bind to a unique site from the acetylcholine orthosteric site, (2010) Molecular Pharmacology 78:648-657.

4. Garbaccio, R.M., Brnardic, E.J., Fraley, M.E., Hartman, G.D., Hutson, P.H.O'Brien, J.A., Magliaro, B. C., Uslaner, J.M., Huszar, S.L., Fillgrove, K.L, Small, J.H., Tang, C., Kuo, Y. and Jacobson, M.A., Tert-Butylphenoxy Oxazolobenzimidazoles: Discovery and Lead Optimization of Selective Positive Allosteric Modulators for the Metabotropic Glutamate 2 Receptor, (2010) ACS Med Chem Letters 20:3129-3133.

5. Brnardic,E.J., Fraley ,M.E., Garbaccio, R.M., Layton, M.E., Sanders, J.M., Culberson, C., Jacobson, M.A., Magliaro, B.C., Hutson, P.H., O'Brien, J.A., Huszar, S.L., Uslaner, J.M., Fillgrove, K.L., Tang, C., Kuo, Y., Sur, S.M., and Hartman, G.D. 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as Positive Allosteric Modulators of mGluR2 for the Treatment of Schizophrenia: Hit-to-Lead Efforts, (2010) Bio.Med. Chem. Lett. 20: 3129-3133.

6. Uslaner,  J.M., Parmentier-Batteur, S., Flick, R.B., Surles, N.O., Lam, J.S.H., McNaughton, C.H., Jacobson, M.A. and Hutson, P.H. Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampus (2009) Neuropharmacology 57:531-538.

7. Ma, L., Seager,M., Wittmann , M., Bickel, D., Burno, M., Jones, K., Kuzmick-Graufelds, V., Xu.G., Pearson,M., McCampbell, A., Gaspar,R., Shughrue,P., Danziger,A., Regan,C., Garson,S., Doran, S., Kreatsoulas,C., Veng,L., Lindsley,C., Shipe,W., Kuduk,S., Jacobson, M., Sur,C., Kinney,G., Seabrook,G., Ray,W. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation (2009) Proc. Natl. Acad. Sci. 106 :15950-15955.

8. Wolkenberg, S.E., Zhao, Z., Wisnoski, D.D., Leister, W.H., O'Brien, J.A., Lemaire, W., Williams, D.L., Jacobson, M.A., Sur, C., Kinney, G.G., Pettibone, D.J., Tiller, P.R., Smith, S., Gibson, C., Ma, B.K., Polsky-Fisher, S.L., Lindsley, C,W. and Hartman, G.D. Discovery of GlyT1 inhibitors with improved pharmacokinetic properties (2009) Biorg.and Med. Chem Lett. 19:1492-1495.

9. Zhao,Z., Leister, W.H., O'Brien,J.A., Leimare, W., Williams, D.L., Jacobson, M.A., Sur, C., Kinney, G.G., Pettibone, D.J., Tiller, P.R., Smith, S., Hartman, G.D., Lindsley. C.W. and Wolkenberg, S.E. Discovery of N-{[1-propylsulfony;]-4-pyridin-2-ylpiperidin-4-yl}methyl}-benzamides as novel, selective and potent GlyT1 inhibitors (2009) Biorg.and Med. Chem Lett. 19:1488-1491.

10. Smith, S.M., Uslaner, J.M., Yao, L., Mullins, C.M., McNaughton, C.H., Huszar, S.L., Pascarella, D.M., Kandebo, M, Hinchliffe, R.M., Sparey, T.J., Jones, B., Brandon, N.J., Venkatraman, S, Young, S, Sachs, N.A., Jacobson, M.A. and Hutson, P.H. The behavioral and neurochemical effects of a novel D-amino acid oxidase inhibitor (pyrrole carboxylic acid, compound 8) and D-serine. (2009) JPET 328:921-930.

Temple University
Moulder Center for Drug Discovery Research

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