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Professor
Department of Neurosciences Case Western Reserve University
School of Medicine, Room E701
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My laboratory studies neurochemical plasticity in adult neurons. We are interested in the ways in which the chemistry of the adult nervous system can change and the functional consequences of such changes. We focus particularly on alterations that occur in response to (1) neural damage and (2) changes in the electrical activity.
Currently, we are focusing on the molecules and cells involved in altering neuronal gene expression in response to axonal injury and in changing the intrinsic growth capacity of these neurons. Our studies focus on sympathetic and sensory neurons. Previous research has established that, when a peripheral neuron’s axon is severed, it decreases its synthesis of a number of proteins involved in neurotransmission and increases its synthesis of other proteins involved in regeneration. We find that, following axotomy, sympathetic neurons in the rat superior cervical ganglion express vasoactive intestinal peptide (VIP), galanin, and pituitary adenylate cyclase-activating polypeptide, three neuropeptides not normally expressed by these neurons. These changes are detected both at the peptide and mRNA levels.
Similar changes occur if adult ganglia are placed in either explant or dissociated cultures, allowing us to use these in vitro systems to study the molecular mechanisms involved. Our studies have shown that these changes in neuropeptide expression are triggered at least in part by the induction of cytokines of the gp130 family, including leukemia inhibitory factor (LIF), and by the reduction of the target-derived trophic factor nerve growth factor (NGF) both of which occur after transection of sympathetic axons. Strikingly, changes in both of these peptides occur in two other types of peripheral neurons after axonal injury, namely, sensory and motor neurons.
These two signals also are involved in triggering an increase in the intrinsic growth capacity of these neurons. We study this effect by using the conditioning lesion response, which we have shown occurs in sympathetic neurons, as it has been shown to occur in sensory and motor neurons.
Another change which occurs in sympathetic and sensory ganglia after axotomy is the influx of macrophages. While macrophage infiltration in the distal stump of a transected peripheral nerve plays an important role in phagocytosing myelin and axonal debris, their role within peripheral ganglia is unknown and this question is an important part of our current research focus.
| Ph.D. Student | Present Position |
|---|---|
| Chauncey W. Bowers, Ph.D. | Assistant Research Scientist Division of Neuroscience Beckman Research Institute The City of Hope 1450 E. Duarte Rd Duarte CA 91010 |
| Nancy Ip, Ph.D. | Chair Professor and Director of the Biotechnology Research Institute Department of Biochemistry Hong Kong University of Science and Technology Clear Water Bay Kowloon, Hong Kong |
| Jaisri R. Lingappa, M.D., Ph.D. | Associate Professor of Pathobiology Adjunct Assistant Professor of Medicine University of Washington Room F161B Box 357238 1959 NE Pacific St. Seattle, WA 98195-7238 |
| Robert P. Mohney, Ph.D. | Project Leader Metabolon Inc 800 Capitola Drive, Suite 1 Durham, NC 27713 |
| Michael Schwarzschild, M.D., Ph.D. | Associate Professor Molecular Neurobiology MGH East, CNY-6, Rm 6024 Bldg 149 13th Street Charlestown MA 02129 |
| Yi Sun, Ph.D. | Associate Professor Department of Psychiatry and Biobehavioral Sciences UCLA Los Angeles, CA |
| Yuefang Zhou, Ph.D. | Assistant Professor Department of Neurology & Psychiatry St. Louis University St. Louis, MO |
| Sarah E Shoemaker, Ph.D. | University of North Carolina Neuroscience Center Chapel Hill, NC |
| Postdoc / R.A. | Present Position |
|---|---|
| Dr. Alcmene Chalazonitis, Ph.D. | Research Scientist Department of Anatomy and Cell Biology Columbia University CPS 630 W. 168th Street New York NY 10032 |
| Vincent A. Chiappinelli, Ph.D. | Chair and Professor of Pharmacology Dept. of Pharmacology George Washington University School of Medicine 2300 Eye Street NW Washington DC 20037 |
| Ralph H. Loring, Ph.D. | Associate Professor Department of Pharmaceutical Sciences Northeastern University 211 Mugar Hall Boston MA 02215 |
| Ann R. Rittenhouse, Ph.D. | Associate Professor Dept. of Physiology University of Massachusetts Medical Center 55 Lake Ave. North Worcester MA 01655 |
| Catherine A. Sasek, Ph.D. | Health Scientist Administrator National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-55 Rockville MD 20857 |
| David W. Schulz, Ph.D. | Manager Pfizer Central Research Department of Neuroscience Groton CT 06340 |
| Annette M. Shadiack, Ph.D. | Director, Preclinical Development Global Alliance for TB Drug Development 40 Wall Street, 24th Floor New York, NY 10005 |
| Kristen Boeshore, Ph.D. | Assistant Professor Biology Department Lebanon Valley College 101 N. College Ave. Annville, PA 17003 |