Graduate Program in Neuroscience

Linda Bambrick, Ph.D.

Paul Fishman, M.D., Ph.D.

Gary Fiskum, Ph.D.

Douglas O. Frost, Ph.D.

Gloria E. Hoffman, Ph.D.

M. Samir Jafri, Ph.D.

Sergei Karnup, MD, PhD, DSc.

Bruce K. Krueger, Ph.D.

Margaret M. McCarthy, Ph.D.

Istvan Merchenthaler, MD, PhD, DSc

Mervyn J. Monteiro, Ph.D.

Teodor Postolache, M.D.

James Russell, M.D.

Robert Schwarcz, Ph.D.

J. Marc Simard, M.D., Ph.D.

Scott M. Thompson, Ph.D.

Ashiwel S. Undie, Ph.D.

Michael W. Vogel, Ph.D.

Paul J. Yarowsky, Ph.D.

Although neuroprotection scientists utilize a wide variety of state-of-the art methods and experimental systems, two common themes underlie much of the research in this area. First, many neurodegenerative disorders can be caused or promoted by inherited gene mutations leading to the production of abnormal brain proteins. Neuroprotection researchers are utilizing a number of systems in which these abnormal genes are inserted into normal cells or living (transgenic) mice in order to study the biological consequences of these mutations. Second, there is strong evidence that many neurodegenerative disorders are characterized by the death of brain cells (neurons, astrocytes, oligodendrocytes, etc.) via a process known as apoptosis by which cells commit suicide. While apoptosis plays an essential role in the development of the normal brain, its occurrence during adult life is abnormal and can cause neurodegenerative disease. Scientists throughout the world, including those in the Neuroprotection Research Focus Group, have been characterizing the complex molecular and cellular process by which brain cells undergo apoptosis with the goal of understanding how to prevent its occurrence. A particular focus at University of Maryland is the mitochondrion, a microscopic organelle inside all cells, once thought to be solely the cells energy source, but now known to also play a critical role in suppressing apoptosis in healthy cells and inducing this form of death in injured cells.

Research by neuroprotection scientists is directed toward identifying and characterizing proteins that maintain neuron survival in the normal brain, as well as those that, when altered by mutation, result in neuron death. Although many of these proteins are found specifically in neurons, some are located in other brain cells such as astrocytes, the metabolic chaperones of neurons, oligodendrocytes, the cells that form the myelin sheath insulation of axons, and cells within the cerebrovascular system providing fuel and oxygen to the brain. The effect of aging and neurotoxins on the levels of these proteins is also being investigated. These proteins are potential targets for drugs that could be used to prevent or treat neurodegenerative disorders. Indeed, neuroprotection researchers are engaged in a number of collaborative relationships with pharmaceutical companies interested in utilizing the discoveries made by these scientists to design novel drugs that are effective against neurological disorders and neurotoxicity.

Examples of neuroprotective interventions under development include the use of drugs, hormones, naturally occurring compounds, and environmental conditions that exhibit the following activities:

In addition to the preclinical neuroprotection research activities, many clinical trials are underway at the University of Maryland Medical Center, the Veteran's Administration Medical Center and the R Adams Cowley Shock Trauma Center testing the efficacy of new drugs and treatment protocols for acute ischemic stroke, head trauma, and a variety of diseases, such as Parkinsons disease. Clinical research at these centers is greatly enhanced by the Center for Clinical Trials at the University of Maryland and by the commitment of the university to expedite the development and implementation of safe and effective therapeutic protocols.

The Neuroprotection Research Focus Group consists of over 50 faculty, postdoctoral fellows, and students within 10 academic departments. Close and effective collaboration between these investigators is promoted by regular Neuroprotection Research Focus Group meetings and numerous research seminars. Total extramural research funding exceeds $10 million per year. Sources of grant support include several different institutes within the National Institutes of Health, other federal agencies, such as the Department of Defense, various research associations, like the American Heart Association and the Alzheimers Association, and numerous pharmaceutical and biotechnology firms.

One unique aspect of the Neuroprotection Research Focus Group is the close interaction between those investigating the pathophysiology of neurodegeneration and the clinicians who treat patients with neurologic and neurodegenerative diseases. The Neuroprotection Research Focus Group consists of both basic and clinical scientists within the University of Maryland School of Medicine, many of whom also work in the University of Maryland Medical Center, the Baltimore VA Medical Center, the R Adams Cowley Shock Trauma Center, and the Maryland Psychiatric Research Center. This extensive network is a valuable resource assisting students, faculty, and extramural sponsors meet the goals of their research missions.

The new millennium presents exciting challenges for the Neuroprotection Research Focus Group. Advances in molecular techniques for identifying abnormal genes and altered gene expression in chronic and acute neurodegenerative disorders enable screening of potential targets for intervention that was not possible a few years ago. The extensive and diverse patient population and the many experimental models of neurotoxicity and neurodegeneration being studied at the University of Maryland provide the resources necessary for such screening. The greater challenge will be to translate the knowledge gained from molecular analyses into an understanding of the mechanisms responsible for neurodegeneration, and into novel approaches for treating or preventing these disorders. Although these goals are formidable, their importance to the health, welfare, and security of our society is immeasurable.