$7,270,484 for Neuroscience Research

How do we form memories? How does the brain move muscle, give us feelings and perform all its miraculous feats? These are some of the daunting questions fueling Ira Black, MD, and his team on their hunt to "uncover the alphabet the brain uses throughout life to effect the changes that occur with experience."

How does a nerve cell establish its identity? How does it know who it is and what it should be doing? Could other cells do that function?

Black, who is chair of the Department of Neuroscience and Cell Biology at UMDNJ-Robert Wood Johnson Medical School (RWJMS), says these queries led his team to convert adult human and rat bone marrow (stem) cells into nerve cells using a relatively simple protocol they developed. These types of cells generally differentiate into bone, cartilage, muscle, tendon and fat. Black's team rocked the research world with the announcement of this feat on August 15, 2000, in the Journal of Neuroscience Research. His ultimate goal is to use this technique- which can produce, in the laboratory, a ready source of a person's own cells for transplantation-to replace dead and dying nerve cells in those with Parkinson's and Alzheimer's diseases, and spinal cord injury.

But creating new nerve cells in culture does not ensure their survival in a living being.

The researchers have successfully taken the next major step by transplanting these cells into the brains and spinal cords of embryonic rats and have determined that the cells survive into the animals' young adulthood and cause them no harm. The team is currently transplanting the neurons into animal models with nervous system damaging diseases to see if, in fact, the cells can function to stop or reverse the disease process. This same work may have applicability in correcting birth defects and congenital abnormalities during embryonic development.

In the spring, the National Institute of Child Health and Human Development awarded Black and his team a five-year, $7,270,484 grant to continue their work into "the molecular mechanisms of development." The researchers' approach is twofold: While advancing their work in transplanting new nerve cells into animal models and analyzing the specific gene mechanisms that allow the conversion of one type of cell to another, they are also identifying and cloning the genes underlying learning and memory.

With colleagues Janet Alder, PhD, and Smita Thakker-Varia, PhD, from RWJMS, and Mark Plummer, PhD, from Rutgers, Black has taken memory neurons from the brain, grown them in cell culture and used trophic (survival) factors to increase the activity of these cells in order to identify the genes associated with enhanced learning and memory. Then working with live animals, they have selectively knocked out one of these genes as a prototype to study the effect on learning and memory. One goal is to identify potential therapeutic targets for improving memory.

"Ultimately, we could replace dead or dying cells in the brain with stem cells, or maybe replace defective genes," he explains. "Individual experiences impact genes in the brain, which then alter brain and nerve function. This gives real rhyme and reason to the term plasticity'the ability of cells to change function in response to environmental stimuli."

Black and his team recently established the Stem Cell Research Center at RWJMS to further investigate stem cell biology and the potential of such cells as therapeutic agents for neurological disorders. The new facility-which is seeking additional financial support-will allow expansion of their efforts.

"I think we're on the threshold of a revolution in medicine. We're talking about replacement, regeneration and recovery of function, not about patching up and giving drugs," says Black.

He says the real payoff is still years away, but states: "The evidence is accumulating that this is realistic. Our goal is to understand the mechanisms responsible for development at all of the various stages of life."