Neuro-ICE engineers stem cells to heal the CNS. | | | Ted Dawson’s lab recently identified a promising drug target for late-onset Parkinson’s, a gene that plays a key role in the pathogenesis of the disease. |
Because the brain is the center of the self,” says Valina Dawson, “the effect of any loss of function can be profound.” Preserving the self, then, is what underlies work within the neuroregeneration and repair division that Dawson co-directs at ICE. More immediately, its researchers aim to learn how stem cells form and take on their unique roles in the CNS and to find how those mechanisms go awry when disease strikes. Guo-Li Ming, for example, explores the mechanisms by which neurons send out axons to other target neurons. When the CNS is injured, biochemical blocks appear that stymie axons, preventing them from reaching their designated partners and making good connections. Ming has been tracking a molecule called MAG that appears to be a key player in this process. Unscrambling MAG’s story will help Ming develop a cell-based therapy to overcome obstacles to axon regeneration in diseases like ALS and multiple sclerosis, or in spinal cord injury. Hongjun Song is investigating how stem cells develop and integrate into the adult nervous system. He’s already discovered that the neurotransmitter GABA, which usually inhibits neuron activity, actually promotes maturation of neuronal stem cells and helps integrate them into the adult brain. Song’s findings have important implications for the use of stem cells in neuronal cell-replacement therapies for degenerative diseases. Meanwhile, stem cells from a genetically engineered mouse are helping Nick Gaiano understand nervous system cancer. Gaiano studies NOTCH, a protein that resides on the surface of stem cells and helps them maintain the ability to differentiate into different types of cells. Gaiano’s basic research on the NOTCH pathway led to a startling finding—85 percent of mice in which NOTCH is artificially stimulated develop choroid plexus brain tumors. The mice are also prone to ocular melanomas, a much more invasive cancer. Clinical researchers recently discovered evidence of NOTCH in human tumor tissue, a sign that this protein pathway may also play a role in human melanomas. Fear, aggression, appetite—all our most basic drives—are regulated by the hypothalamus. Seth Blackshaw, who uses high-throughput technology to scan for genes important in development and disease, recently began large-scale expression profiling of the hypothalamus, studies that have already turned up provocative leads. He’s uncovered evidence that certain types of injury initiate development of neurons in the adult hypothalamus. In the process, he found a new candidate adult stem cell population. Additionally, the Blackshaw lab has identified genes that appear to regulate the development of retinal neurons. Neuro-ICE co-directors Ted and Valina Dawson have made major progress in the past two years identifying genes and resulting proteins that help protect the healthy brain. Using this new knowledge, they’re seeking drugs to turn on protein expression that could help the brain heal itself after injury or disease strike. Valina Dawson hopes to develop a drug that could specifically ameliorate loss of brain function after stroke. The Dawsons have also identified genes that catalyze the death of certain types of brain cells. Together, they are discovering how a new gene—LRRK2—may kill dopamine-producing neurons in Parkinson’s disease. “We think it’s going to be a very important gene,” she says. | 
