Miami Project Researcher Receives $6M NINDS Grant
Jae K. Lee, Ph.D., professor in the Department of Neurological Surgery and The Miami Project to Cure Paralysis, was recently awarded a $6 million grant from the National Institute of Neurological Disorders and Stroke (NINDS) for his RM1 Interdisciplinary Team Science Grant to advance cellular therapies for spinal cord injuries. NINDS, part of the National Institutes of Health, will fund the project for five years.
The study, titled “Targeting cell-type specific disease phenotypes to promote CNS repair,” will develop a novel drug discovery platform that uses single cell RNAseq datasets to identify compounds that can potentially reverse cell-type specific disease signatures and use advanced drug delivery systems to target these specific cell types at the spinal cord injury site.
Despite decades of intensive research, there are currently no disease-modifying therapies to treat spinal cord injury. One major reason for this dire unmet need is the heterogeneity of the cells that comprise the injury site. The cell types and their cellular states vary widely, depending on their location around the injury site as well as the time after injury. Therapeutic molecules that target one cell type may be contraindicated for another cell type, thereby masking any potential beneficial effects. Current treatment strategies largely ignore this problem.
Dr. Lee is tackling this important issue through this recently awarded Interdisciplinary Team Science Grant. The collaboration includes Dr. Lee; Nagi Ayad, Ph.D., professor in the Department of Oncology of the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center; and Ki-Bum Lee, Ph.D., distinguished professor in the Department of Chemistry and Chemical Biology at Rutgers University.
The team will use a novel drug discovery platform that analyzes the genetic signature of every cell type known to exist at the spinal cord injury site, to identify compounds that are predicted to reverse the disease signature of specific cell types.
“Using advanced sequencing technologies, we have been able to obtain the gene expression profiles of every cell type that exists at the spinal cord injury site,” said Dr. Lee. “Now, using a novel bioinformatic platform developed by Dr. Nagi Ayad, we have the opportunity to leverage this large dataset for drug development purposes.
“Everyone recognizes that treating spinal cord injury is going to take a combinatorial approach,” Dr. Lee added, “so we are going to combine the expertise of three laboratories that span three completely different fields to take a novel approach to developing therapeutics for spinal cord injury.”
Identifying a cell-type specific drug is only part of the solution — another challenge is delivering that drug to the intended cell target, said Dr. Lee. This is where Dr. Ki-Bum Lee will use his decades of experience to develop an advanced drug delivery system capable of highly efficient cell-type targeted delivery with stimuli-responsive drug release at the spinal cord injury site.