UMDNJ Researcher Strives to Reverse, Prevent
Disorders in Infants and Adults
NEW BRUNSWICK — Patrizia Casaccia-Bonnefil, MD, PhD, associate professor of neuroscience and member of The Cancer Institute of New Jersey at UMDNJ-Robert Wood Johnson Medical School, and her team of researchers have identified new molecular signals responsible for brain development and repair. These mechanisms may be utilized in therapies aimed at reversing damage of oligodendrocytes occurring in premature babies, as well as in adult patients affected by multiple sclerosis, brain trauma and spinal cord injury.
Dr. Casaccia-Bonnefil’s laboratory recently discovered that disease states and old age modify the properties of neural progenitors rendering them unable to mature normally, thereby leaving nerve cells unprotected. Progenitors are immature cells that develop into specific cell types, such as oligodendrocytes, which are the cells that produce myelin, the fatty substance that insulates the nerve fibers of the brain and spinal cord. The damaged nerve cells lead to the symptoms associated with multiple sclerosis, as well as other neurological disorders. Applying this discovery, Dr. Casaccia-Bonnefil’s research is aimed at understanding how these cells can be stimulated to repair the damaged adult brain.
“In an effort to prevent, protect and repair myelin, my research is aimed at defining novel therapies for the treatment of neurological defects associated with the development of premature myelin-producing oligodendrocytes and other conditions associated with deficits in myelin formation, including maternal diet, hormonal state or exposure to toxins,” Dr. Casaccia-Bonnefil said. “By doing so, we can work to restore nerve function and reverse the effects of neurodegenerative disorders.”
Dr. Casaccia-Bonnefil’s team also has identified several molecular components that inhibit proper cell development by affecting epigenetic memory. Epigenetic memory is an inheritable mechanism of gene expression (the process by which the inheritable information is transcribed and modified) that allows each cell to have a specific identity. As published in The Journal of Neuroscience, the loss of epigenetic memory slows down the maturation of progenitors into myelin-producing oligodendrocytes. In addition, in a recent issue of Neuron, Dr. Casaccia-Bonnefil’s laboratory identified a molecule called HDAC and a transcription factor known as Ying Yang 1 as essential for the normal development of oligodendrocytes. Deactivating Ying Yang 1 during cell development completely inhibits myelin formation.
“These seminal discoveries may significantly impact future therapeutic strategies for neurodegenerative disorders,” said Dr. Casaccia-Bonnefil.
Dr. Casaccia-Bonnefil is now studying how these findings can be translated specifically into treatment of diseases affecting young adults with multiple sclerosis or brain injury and affecting premature babies and neonates (infants less than four weeks old) with damaged myelin.
An internationally-recognized researcher, Dr. Casaccia-Bonnefil’s studies are funded by the National Institute of Health, the National Multiple Sclerosis Society, the New Jersey Commission of Science and Technology, the Christopher and Dana Reeve Foundation, and the MS Research Foundation (New Jersey).
UMDNJ is the nation's largest free-standing public health sciences university with more than 5,700 students attending the state's three medical schools, its only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and its only school of public health, on five campuses. Last year, there were more than two million patient visits to UMDNJ facilities and faculty at campuses in Newark, New Brunswick/Piscataway, Scotch Plains, Camden and Stratford. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, a mental health and addiction services network.