From lab to clinic in the Sunshine State
First five projects named to pilot Florida Translational Research Program
ORLANDO—Sanford-Burnham Medical Research Institute hasselected five research projects to initiate the Florida Translational ResearchProgram (FTRP), the goal of which is to advance drug discovery and build arobust network of the state's existing drug discovery and developmentresources.
The projects that were awarded the five slots available inthe FTRP's inaugural year include three related to discovering new therapeuticsfor cancer, one aimed at treating diabetes and one related to combatingobesity. Dr. Claes Wahlestedt and a team at the University of Miami will searchfor chemical compounds to disrupt MLL3, which is indicated in the developmentof breast cancer, colon cancer and several leukemias. Dr. Daiqing Liao willlead a team of researchers at the University of Florida in the search forinhibitors of acetyltransferase p300, which they have demonstrated is a masterregulator of cancer-cell survival. Dr. Cristina Fernandez-Valle and her team atthe University of Central Florida will be searching for compounds that blockthe protein merlin, which has a similar function. Dr. Patricia McDonald atScripps Florida and Sanford-Burnham will collaborate to identify molecules thatinhibit GPR21, a protein known to reduce the effects of insulin. Finally, Dr.Fraydoon Rastinejad and the team at his Sanford-Burnham lab will search forinhibitors of Rev-Erba and Rev-Erbb, proteins that control metabolism and theexpansion of fat cells.
"We selected these projects based on scientific merit,technical feasibility and potential for commercialization," says Dr. LaytonSmith, director of Drug Discovery Florida at Sanford-Burnham. "In this firstrun, we were looking for assays that were HTS-ready."
Sanford-Burnham will be extensively involved in each ofthese projects, acting as an important node in the network it is administering,and will maintain a dedicated team to manage the portfolio. The selectedresearch programs can take advantage of Sanford-Burnham's expertise andinfrastructure in ultrahigh-throughput screening. Sanford-Burnham scientistswill conduct the wet-lab work, high-throughput assays and screening using theorganization's small-molecule library. Afterward, the projects will return tothe investigators at the partnering institutions for further analysis, otherassays and in-depth investigations not requiring high-throughput screening.
A successful project will yield results of high-throughputscreenings with validated hits in the assays with activity at the intendedpathway or target. These first five collaborations, however, are only the firststep.
"We had more than 50 applicants with projects in varyingstages of readiness," says Smith. "It told us that assistance with assaypreparation is an enormous unmet need—there's a pent-up desire to dosmall-molecule screening. In realizing that, we realized we could help todevelop a pipeline."
In the years ahead, the FTRP will aim to develop such apipeline of potential new medicines based on laboratory research discoveries.The focus in this pilot year was on high-throughput-ready assays, but as theprogram expands it will accept a greater diversity of proposals, including morecomprehensive projects that may have a chemical component, those not yet readyfor high-throughput screening and even some that may require assay developmentservices from Sanford-Burnham.
The number of projects is expected to increase in 2014.
"Everyone knows drug discovery is expensive and prone tofailures, and no company or institution can have all the experts in all diseaseareas," says Smith. "We're pioneering a virtual model for advancingtechnologies from the lab to the clinic building on existing strengths andtechnologies 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 resourcesin the state, create networks among research and clinical entities and hold thepotential for long-term economic impact. Sanford-Burnham's expertise andinfrastructure related to drug development as well as its existingrelationships with various institutions throughout the state made it anattractive choice for state funding to administer the FTRP.
Early work on the first of the FTRP collaborations began inFebruary 2013, and the investigators expect to complete all of the projects bythe end of the year.