Steadying Nerves

(Left: Scott Brady, PhD, Head of Anatomy and Cell Biology )

Anatomy and Cell Biology Head Scott Brady Leads the Quest to Understand Neurological Disorders

Typically microscopic in width but up to a meter in length, axons are the part of nerve cells that carry neurological signals throughout the body, and they’ve fascinated Scott Brady, PhD, throughout his career. “I wanted to understand how a neuron that large could develop and maintain itself for 75 or 80 years,” says Brady, head of the UIC department of anatomy and cell biology. “It leads to the question of what happens when things go wrong.”

Brady has made understanding how neurological processes go wrong in diseases such as Alzheimer’s, Parkinson’s and Huntington’s the focus of the department’s research agenda. “These diseases are major health issues for which there are effectively no treatments available,” observes Brady. “They have an enormous cost on both a personal and a societal level.”

Brady is leading this endeavor at a crucial juncture. Because many neurodegenerative diseases are age-related, they are likely to become more prevalent as the Baby Boomers grow older. On the other hand, rapid advancements in molecular science offer the promise of a whole new class of therapies. Since coming to the College of Medicine from the University of Texas Southwestern Medical Centerin 2003, Brady has built a multinational team of young researchers to conduct this cutting-edge work, hiring seven of the department’s 17 current faculty members. The department presently is conducting more than a dozen major studies, supported by more than $25 million in funding, including $21.9 million from the National Institutes of Health.

Brady’s own research builds on a discovery he made shortly after completing his PhD at the University of Southern California  in 1978. While studying the materials moving through the giant axon of squid during his postdoctoral work at the Marine Biological Laboratory in Woods Hole, Mass., and Case Western Reserve University in Cleveland, he discovered kinesins, a kind of molecular motor involved in axonal transport. Up to nearly one millimeter wide, the giant axon of squid is 1,000 times larger than those in most mammals, making it a frequent model for studies of neurological processes.

Since then, Brady has focused his research on better understanding the structure, regulation and molecular biology of kinesins in the neuron. He currently is exploring the roles of axonal transport and the regulation of molecular motors in Alzheimer’s, Parkinson’s, Huntington’s and other adult-onset neurodegenerative diseases. “These processes are important because many of the neurological diseases once thought to be diseases of cell death are, understood more explicitly, diseases of abnormal axonal transport,” Brady reflects. “The thinking goes that if you can restore the transport, you can save the cell and defeat the disease.” His work is supported regularly by the NIH, Muscular Dystrophy Association and ALS Association.

He’s equally passionate about supporting his young researchers in their own novel explorations. “Scott loves to see people succeed,” says Mary Jo LaDu, PhD ’91, associate professor of anatomy and cell biology.

Recruited from the ENH Research Institute, the research arm of Northwestern University and Evanston Northwestern Healthcare, LaDu is studying the interactions between the protein apoE4, the primary genetic risk factor for Alzheimer’s disease, and Abeta peptide, the only known genetic causative factor for the disease. She’s using a variety of techniques to explore how these proteins can be manipulated to treat the disease.

Since the beginning of 2009, LaDu has been directing a five-site, $11.5 million NIH study centered at UIC examining how apoE4 modulates the function of nerves in the brain.

Brady credits LaDu’s work for helping to determine that it is not the accumulation of plaques that triggers Alzheimer’s disease, as commonly was thought, but rather a component part of plaques, small soluble oligomers, that wreak havoc upon the human brain.

Other recent recruits reflect Brady’s commitment to both diversity and innovative research science. Orly Lazarov, PhD, a native of Israel who had been a research fellow at the University of Chicago prior to joining the department, is studying the molecular mechanisms that are common to both neurogenesis—the production of nerve cells—and Alzheimer’s disease. Hailing from Buenos Aires by way of UCLA and a gene therapy institute in Milan, Ernesto Bongarzone, PhD, is examining the root causes of neuronal damage in childhood diseases such as leukodystrophies and adult diseases such as multiple sclerosis. Gerardo Morfini, PhD, an Argentinean who came with Brady from University of Texas Southwestern Medical Center, is focusing on how regulatory pathways in the brain are affected by pathogenic proteins associated with Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (Lou Gehrig’s disease) and other diseases. (All three researchers are assistant professors in anatomy and cell biology.)

“One advantage of bringing together multiple research groups that share an interest in neurodegenerative diseases is that the whole becomes greater than the sum of its parts,” Brady notes. “Each of these recruits to our departmental faculty now has collaborations within the department. The resulting exchange of ideas and approaches creates an opportunity to answer questions that individual laboratories might not undertake.”

One example of this interaction is a recent publication in the Proceedings of the National Academy of Sciences that included members of the Brady, LaDu and Morfini laboratories among its authors. The study received attention nationally because it provided new insights into how the small oligomeric form of the Abeta peptide damages neurons in Alzheimer’s disease patients and identified a promising new set of therapeutic targets.

Brady sees the concentration in neuroscience the department has developed over the six years he’s been at its helm as a stepping stone to his ultimate goal: establishing a center for the study of neurodegenerative disease at UIC. “A center would enable us to recruit a critical mass of researchers who share questions and methods,” he says. “That kind of collaboration would allow us to make progress in our research more quickly than we can individually, and speed the development of potential treatments for these diseases.”