Shrinking pipelines and major cutbacks in CNS drug discovery in pharmaceutical companies have led to an increased awareness of the critical need for NIH-supported institutions to participate in early stage drug discovery research. NIH has initiated several strategic efforts to advance and de-risk novel therapeutic strategies by supporting early stage drug discovery that can providing data sets, proof-of-concept compounds, and in some cases drug leads or drug candidates that can be advanced towards clinical development in an industry setting. In addition to early stage drug discovery, this includes investments in discovery of clinical biomarkers and the advancement of novel molecules into clinical proof of concept studies. However, there are a number of challenges in establishing these new initiatives. Drug discovery is a unique and highly integrated discipline that has not traditionally been a major focus of NIH-supported institutions. For this reason, training of drug discovery scientists has not been a traditional focus of academic training programs. Instead, expertise and training in drug discovery occurs in pharmaceutical companies, where entry-level PhD scientists are trained across a broad range of disciplines that are key components of successful drug discovery research. For emerging efforts in academic drug discovery to succeed, it will be critical to provide outstanding training to equip young scientists with the skill sets required to build successful academic careers in which they incorporate aspects of drug discovery in their research or make drug discovery research a primary career focus. Vanderbilt has established world class academic CNS drug discovery program that utilizes the major infrastructure and expertise that is traditionally found only in industry settings. The program is enjoying tremendous success in driving fundamental advances in neuroscience and translational research through discovery and optimization of high quality research probes, drug leads, and clinical development candidates and using these tools to push the boundaries of our understanding of CNS systems that may be important for multiple brain disorders. This is providing our trainees with unique multidisciplinary and highly integrated CNS drug discovery training. We propose establishing a training program that builds on this success to systematically train postdoctoral fellows in multiple aspects of drug discovery research. Training opportunities include training in HTS and molecular pharmacology, medicinal chemistry, drug metabolism and pharmacokinetics, behavioral pharmacology, biomarker discovery, and other key sub disciplines that are critical for CNS drug discovery. Each project is pursued in a close collaboration between multiple laboratories in the program and provides an unprecedented opportunity for the highest level training in academic drug discovery.

Public Health Relevance

We propose a comprehensive training program for postdoctoral trainees that will provide extensive training in CNS drug discovery research. Trainees will work in a unique training environment that is made possible through the combined resources and expertise of the Vanderbilt Program in Drug Discovery, along with collaborating departments and centers, including the Department of Pharmacology, Center for Molecular Neuroscience, Vanderbilt Institute for Imaging Science, among others. This program provides a unique opportunity for postdoctoral fellows to receive unprecedented training in multiple facets of CNS drug discovery research within the context of a highly integrated drug discovery environment led by highly accomplished drug discovery scientists.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Institutional National Research Service Award (T32)
Project #
5T32MH093366-04
Application #
8661292
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Rosemond, Erica K
Project Start
2011-07-04
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Nashville
State
TN
Country
United States
Zip Code
37212
Moran, Sean P; Cho, Hyekyung P; Maksymetz, James et al. (2018) PF-06827443 Displays Robust Allosteric Agonist and Positive Allosteric Modulator Activity in High Receptor Reserve and Native Systems. ACS Chem Neurosci 9:2218-2224
Joffe, Max E; Santiago, Chiaki I; Engers, Julie L et al. (2017) Metabotropic glutamate receptor subtype 3 gates acute stress-induced dysregulation of amygdalo-cortical function. Mol Psychiatry :
O'Brien, Daniel E; Conn, P Jeffrey (2016) Neurobiological Insights from mGlu Receptor Allosteric Modulation. Int J Neuropsychopharmacol 19:
Gould, Robert W; Nedelcovych, Michael T; Gong, Xuewen et al. (2016) State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 - Relation to antipsychotic-like drug effects. Neuropharmacology 102:244-53
Gorden, D Lee; Myers, David S; Ivanova, Pavlina T et al. (2015) Biomarkers of NAFLD progression: a lipidomics approach to an epidemic. J Lipid Res 56:722-36
Nedelcovych, Michael T; Gould, Robert W; Zhan, Xiaoyan et al. (2015) A rodent model of traumatic stress induces lasting sleep and quantitative electroencephalographic disturbances. ACS Chem Neurosci 6:485-93
Gould, R W; Dencker, D; Grannan, M et al. (2015) Role for the M1 Muscarinic Acetylcholine Receptor in Top-Down Cognitive Processing Using a Touchscreen Visual Discrimination Task in Mice. ACS Chem Neurosci 6:1683-95
Mathews, Thomas P; Hill, Salisha; Rose, Kristie L et al. (2015) Human phospholipase D activity transiently regulates pyrimidine biosynthesis in malignant gliomas. ACS Chem Biol 10:1258-68
Jalan-Sakrikar, Nidhi; Field, Julie R; Klar, Rebecca et al. (2014) Identification of positive allosteric modulators VU0155094 (ML397) and VU0422288 (ML396) reveals new insights into the biology of metabotropic glutamate receptor 7. ACS Chem Neurosci 5:1221-37
Morris, Lindsey C; Days, Emily L; Turney, Maxine et al. (2014) A Duplexed High-Throughput Screen to Identify Allosteric Modulators of the Glucagon-Like Peptide 1 and Glucagon Receptors. J Biomol Screen 19:847-58

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