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From lab to clinic in the Sunshine State
May 2013
by Jim Cirigliano  |  Email the author
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ORLANDO—Sanford-Burnham Medical Research Institute has selected five research projects to initiate the Florida Translational Research Program (FTRP), the goal of which is to advance drug discovery and build a robust network of the state's existing drug discovery and development resources.
 
The projects that were awarded the five slots available in the FTRP's inaugural year include three related to discovering new therapeutics for cancer, one aimed at treating diabetes and one related to combating obesity. Dr. Claes Wahlestedt and a team at the University of Miami will search for chemical compounds to disrupt MLL3, which is indicated in the development of breast cancer, colon cancer and several leukemias. Dr. Daiqing Liao will lead a team of researchers at the University of Florida in the search for inhibitors of acetyltransferase p300, which they have demonstrated is a master regulator of cancer-cell survival. Dr. Cristina Fernandez-Valle and her team at the University of Central Florida will be searching for compounds that block the protein merlin, which has a similar function. Dr. Patricia McDonald at Scripps Florida and Sanford-Burnham will collaborate to identify molecules that inhibit GPR21, a protein known to reduce the effects of insulin. Finally, Dr. Fraydoon Rastinejad and the team at his Sanford-Burnham lab will search for inhibitors of Rev-Erba and Rev-Erbb, proteins that control metabolism and the expansion of fat cells.   
 
"We selected these projects based on scientific merit, technical feasibility and potential for commercialization," says Dr. Layton Smith, director of Drug Discovery Florida at Sanford- Burnham. "In this first run, we were looking for assays that were HTS-ready."
 
Sanford- Burnham will be extensively involved in each of these projects, acting as an important node in the network it is administering, and will maintain a dedicated team to manage the portfolio. The selected research programs can take advantage of Sanford-Burnham's expertise and infrastructure in ultrahigh-throughput screening. Sanford-Burnham scientists will conduct the wet-lab work, high-throughput assays and screening using the organization 's small-molecule library. Afterward, the projects will return to the investigators at the partnering institutions for further analysis, other assays and in-depth investigations not requiring high-throughput screening.  
 
A successful project will yield results of high-throughput screenings with validated hits in the assays with activity at the intended pathway or target. These first five collaborations, however, are only the first step.  
 
"We had more than 50 applicants with projects in varying stages of readiness," says Smith. "It told us that assistance with assay preparation is an enormous unmet need—there's a pent-up desire to do small-molecule screening. In realizing that, we realized we could help to develop a pipeline."  
 
In the years ahead, the FTRP will aim to develop such a pipeline of potential new medicines based on laboratory research discoveries. The focus in this pilot year was on high-throughput-ready assays, but as the program expands it will accept a greater diversity of proposals, including more comprehensive projects that may have a chemical component, those not yet ready for high-throughput screening and even some that may require assay development services from Sanford-Burnham.  
 
The number of projects is expected to increase in 2014.  
 
"Everyone knows drug discovery is expensive and prone to failures, and no company or institution can have all the experts in all disease areas," says Smith. "We're pioneering a virtual model for advancing technologies from the lab to the clinic building on existing strengths and technologies and finding the right partnerships."
 
"To my knowledge, no other state is doing this," says Smith.  
 
Florida Gov. Rick Scott issued a call in 2011 for bold, innovative projects that would leverage the existing drug discovery resources in the state, create networks among research and clinical entities and hold the potential for long-term economic impact. Sanford-Burnham's expertise and infrastructure related to drug development as well as its existing relationships with various institutions throughout the state made it an attractive choice for state funding to administer the FTRP.
 
Early work on the first of the FTRP collaborations began in February 2013, and the investigators expect to complete all of the projects by the end of the year.
 
Code: E051318

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