The Vanderbilt Institute of Chemical Biology (VICB) is a multi- and trans-disciplinary institute within the Basic Sciences of the Vanderbilt School of Medicine. Founded by Larry Marnett and Ned Porter in 2002, the VICB’s stated mission was to “establish research and education programs in the application of chemical technologies to important biological problems”. The location and timing for embarking on such a mission could not have been better.
A productive atmosphere
Unlike the vast majority of universities in the United States, Vanderbilt’s College of Arts and Sciences and School of Medicine share a single campus, an arrangement that fostered an unusually productive atmosphere of collaboration across multiple disciplines in the biomedical sciences. Realizing the benefits of this arrangement, Vanderbilt leadership had established the Academic Venture Capital Fund (AVCF) to provide $100 million for investment in trans-institutional initiatives. The VICB was one initiative to benefit from this AFCF support as it rapidly promoted multi-disciplinary programs in chemical biology across the campus.
Key to the early success of the VICB was the combination of AVCF funds with contributions from individual departments to support the recruitment of 20 new faculty members with expertise in fields related to chemical biology. These included synthetic and medicinal chemistry, natural products discovery, high-throughput screening, computational chemistry, nanotechnology, pharmacology, and metabolomics. The new recruits rapidly integrated into the Vanderbilt research community, joining with 55 incumbent faculty to create the VICB membership.
To promote molecular probe discovery, the foundation of chemical biology research, the VICB established core laboratories in high-throughput screening and chemical synthesis. Once again, the Institute benefitted from excellent timing, as these efforts coincided with the inauguration of the National Institute of Health’s Roadmap Molecular Libraries and Imaging Initiative in 2004. This initiative included establishment of the Molecular Libraries Screening Center Network, which funded 10 high-throughput screening facilities across the country. The VICB’s HTS Core, under the direction of Dave Weaver, was one of those original MLSCN facilities, and it benefitted greatly from the NIH funding, and the experience of working within the Network during its formative years. Then, when the NIH expanded the program to the Molecular Libraries Probe Centers Network, the VICB’s Chemical Synthesis Core, under the direction of Craig Lindsley, became one of only two Specialized Chemistry Centers in the nation. Soon thereafter, the Synthesis Core, under the direction of Gary Sulikowski and Alex Waterson, became a Specialized Chemistry Center in the National Cancer Institute’s Chemical Biology Consortium. Now well established, the HTS Core (directed by Paige Vinson) and Chemical Synthesis Core (directed by Gary Sulikowski) join with the Antibody and Protein Resource (VAPR, directed by Rob Carnahan) and the Small Molecule NMR Core (directed by Don Stec) to provide VICB members with the capabilities needed to screen, characterize, and synthesize the small and large molecule probes that are so critical to successful chemical biology research.
The VICB established educational programs to increase awareness of chemical biology at Vanderbilt and to train the next generation of researchers. The VICB Seminar Program brings top chemical biologists from around the world to campus and also highlights major accomplishments by Vanderbilt faculty. The Seminar Program serves as the focal point for one of three graduate levels courses in chemical biology that are offered by Institute faculty. The NIH-funded Integrative Training in Therapeutic Discovery and Chemical Biology Interface Training Grants have supported numerous graduate students and postdoctoral fellows in chemical biology, while the NSF-sponsored Research Experiences for Undergraduates program brings undergraduate students to campus each summer to work in VICB member laboratories. The annual Research Symposium, planned and conducted by students, provides a forum for the presentation of their latest research, and the Chemical Biology Association of Students provides an opportunity to socialize. Students interested in formalizing their training may complete the Chemical Biology Certificate Program.
The VICB in the forefront
In the 14+ years since its inception, the VICB has had a major impact, catapulting Vanderbilt to the forefront of chemical biology and drug discovery nationally and internationally. It provided the incubator from which Jeff Conn created his highly productive Vanderbilt Center for Neuroscience Drug Discovery. It provides ongoing support for Steve Fesik’s Cancer Drug Discovery Program. Numerous additional drug and molecular probe discovery efforts are thriving on the Vanderbilt campus. Included are:
- Alex Brown’s collaboration with Craig Lindsley to identify isoform-selective inhibitors of phospholipase D.
- Erik Skaar’s work to identify new antibiotics to combat drug-resistant bacterial infections.
- Larry Marnett’s collaboration with Sachin Patel leading to the discovery of substrate-selective COX-2 inhibitors that act as anti-anxiety agents.
- Charles Hong’s discovery of modulators of bone morphogenic protein signaling.
- Larry Zweibel’s work on allosteric modulators of olfactory signaling in mosquitoes.
- Ethan Lee’s research into the mechanism of action of novel inhibitors of Wnt pathway signaling.
- Jerod Denton’s and David Weaver’s discovery of novel inhibitors of potassium channel function.
- David Wright’s work with Rick Haselton to develop low resource methods to improve malaria diagnosis.
- Charles Manning’s discovery of PET imaging agents to identify apoptotic cells in vivo.
- Roger Cone’s work to discover modulators of melanocortin receptor signaling.
These promising discoveries will impact basic science research in a wide range of diseases, including cancer, obesity, diabetes, epilepsy, malaria, bacterial infection, and neuropsychiatric diseases. Many of the molecular probes already discovered also provide lead molecules for ultimate translation to the clinic.
The VICB provides a vibrant interdisciplinary environment that fosters new discovery and research innovation at Vanderbilt. It will be critical to the future exploration of new dimensions for successful multi-investigator initiatives and the ongoing integration of chemical biology education and research into disease-focused programs across the Vanderbilt campus. Going forward, under the leadership of Director Larry Marnett and Associate Directors Eric Skaar, Gary Sulikowski, Brian Bachmann, Alex Brown, and Michelle Sulikowski, the VICB remains committed to its mission of harnessing the power of chemistry to improve human health.