The Florida Translational Research Program (FTRP), an early drug discovery initiative funded by the state of Florida, has proven crucial in advancing research and securing out-of-state funding for investigators at SBP and collaborating institutions. During the current legislative session, SBP is seeking renewed funding of the three-year program after a budget hiatus in 2015 put numerous investigations on hold.
Through the FTRP, discoveries emerging from research labs statewide are enhanced at SBP’s drug discovery center to create a pipeline of potential new medicines to fight cancer, Alzheimer’s disease, diabetes and other diseases. The Prebys Center’s robotic systems and drug discovery experts screen potential drug candidates on a scale tens of thousands of times larger than would be possible in a traditional lab. For many researchers, the data generated is sufficient to attract additional funding in the form of grants and industry partnerships.
Fraydoon Rastinejad, PhD, professor in the Integrative Metabolism Program, received initial FTRP support that led to a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to conduct high-throughput screening. His team is looking for small-molecule modulators of nuclear receptors that control metabolism and circadian regulation, which should lead to novel therapies for diet-induced obesity.
“Such an ambitious drug discovery project would not be possible without the resources of the Prebys Center,” states Rastinejad. “No other institution or pharmaceutical company has searched for drugs that act on these receptors, so we worked with the Center staff to develop and standardize novel assays to identify compounds that activate or inhibit them.”
Similarly, Pamela McLean, PhD, of the Mayo Clinic in Jacksonville, FL, credits her collaboration with SBP (via the FTRP) for her recent award from the Michael J. Fox Foundation to find compounds that block early steps in the development of Parkinson’s disease. “Based on the preliminary data from our work with the Prebys Center, the MJFF doubled its initial award to fund further screening of 320,000 compounds from the NIH collection.”
For Keith Choe, FTRP-sponsored research led to new intellectual property in the form of a patent application by the University of Florida on the use of the laboratory model organism C. elegans to screen potential drugs to treat parasitic worm infections. Gastrointestinal (GI) nematode infections affect 25% of the human population worldwide, and cause anemia and malnutrition and increase susceptibility to other serious infections such as tuberculosis and HIV. Such new drugs are urgently needed to combat the worms’ increasing resistance to existing anti-parasitics.
SBP’s high-throughput capabilities are so cutting-edge that some researchers are pursuing new lines of research that may benefit future FTRP projects. For example, Siobhan Malany, PhD, director of Translational Biology, Lake Nona, won a grant from the Air Force to assess the potential toxicity of environmental chemicals in human cells derived from induced pluripotent stem cells (iPSCs). Testing in human cells should give a more reliable indication of whether the chemicals are harmful than the traditional approach using rodent models.
“This program was funded because of our earlier work developing the assays in iPSC-derived cells. The Air Force seeks to develop an integrated platform across multiple human cell types for rapid toxicological screens, and our initial findings have been promising,” states Malany.
The diversity of the FTRP projects—in cancer, obesity, diabetes, neurodegeneration and others—and the success metrics—generating additional grants, patents and publications—illustrate the program and the SBP Prebys Center’s continued potential to impact human health through the discovery of new therapeutics.