Paul M. Carvey, Ph.D. Professor of Pharmacology and Neurological Sciences Chairman of Pharmacology Acting Dean of the Graduate College
		Education B.S. (1972) – Creighton University (Biology, Psychology) M.S. (1974) – Creighton University (Physiology) Ph. D. (1983) – Rush University (Neuropharmacology)

Contact Information Address: Rush University 2242 West Harrison St. (Suite 260) Chicago, IL 60612 Business Phone: (312) 563-2563 Business FAX: (312) 563-3552 E-mail Address: pcarvey@rush.edu Research Interests Dr. Carvey has several research interests, although all focus on the dopamine (DA) neuron and its relationship to Parkinson’s disease (PD). He has studied, in tissue culture or animals, every single drug currently used in PD patients. His early research career focused on the concepts of pharmacological denervation and agonist-induced hypersensitivity states responsible for dyskinesias. Together with his mentor Harold Klawans, they advanced the notion that Tardive Dyskinesia was a consequence of DA receptor site up-regulation, and further that the propensity for developing Tardive Dyskinesia was a dose, duration of treatment, and type of neuroleptic effect of chronic therapy. He also identified a prominent role for the lateral habenula in antipsychotic therapy. Later he studied the potential relationship between autoimmunity and DA neuron degeneration in PD. In the later 80s and early nineties, he published several articles on the adrenal-medulla-to-brain transplant concept and proposed that the improvement seen in patients was a consequence of alterations in trophic activity. As part of this work, he demonstrated that chronic alterations in neurotransmitter tone, induced by drug treatment, led to compensatory alterations in target-derived neurotrophic activity that altered the cytoarchitectural integrity of the nigro-striatal pathway. He was also centrally involved with the concept that D-3 DA receptor agonists were not only effective in ameliorating symptoms of PD, but neuroprotective through trophic alterations as well. This animal work was instrumental in the design of prospective studies in humans verifying this principle. His work then turned to identifying the factor(s) responsible for converting stem cells into DA neurons. He showed that hematopoietic cytokines, and in particular, Interleukin 1, were centrally involved with this process thereby advancing the notion that molecules involved in regulating stem cell expansion and lineage restriction in the periphery, may be at work within the CNS as well. In the past several years, he has focused his attention on the roles of pro-inflammatory cytokines within the CNS. He has shown that prenatal infections, and in particular bacterial vaginosis which produces increased levels of the bacteriotoxin lipopolysaccharide (LPS), can lead to the birth of animals with fewer than normal DA neurons. He is in the process of verifying the hypothesis that animals born with fewer than normal DA neurons will develop a slowly progressive DA cell loss as they age, and are more sensitive to the neurotoxic effects of environmental toxins such as 6-hydroxydopamine, rotenone, dieldrin, and paraquat. He has proposed that prenatal exposure to LPS leads to a permanent alteration in the transcription of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFa). This epigenetic effect is likely to have significant impact on understanding a variety of diseases, and points to the possibility that prenatal neurotoxin exposure is an overlooked area of disease etiology. Confocal image of DA neurons in mesencephalic cultures expressing TNFR-1 and R-2 receptors (McGuire et al. Exper Neurol 169(2):219-230, 2001.) THir immunostains of ventral mesencephalon from animals exposed to LPS prenatally (LPS) or Hank’s Balanced Salt Solution (HBSS; Saline) at E10.5. Animals were then exposed to 60HDA at P99 or vehicle. Animals were sacrificed at P120. Representative Publications Drug Action in the Central Nervous System. P.M. Carvey, Ph.D. Oxford University Press, New York, NY. (1998). Ling, Z.D. H.C. Robie, C.W. Tong, and P.M. Carvey: Both the antioxidant and D3 agonist actions of pramipexole mediate its neuroprotective actions in mesencephalic cultures. J. Pharm. Exp. Ther. 289:202-210,1999. Vu, TQ, Ling, ZD, Ma, SY, Robie, HC, Tong, CW, Chen, EY, Lipton, JW, and Carvey, PM. Pramipexole attenuates the dopaminergic cell loss induced by intraventricular 6-hydroxydopamine. Journal of Neural Transmission, 107:(2), 159-176, 2000. Carvey, Paul M., ZaoDung Ling, Carol E. Sortwell, Mark R. Pitzer, Susan O. McGuire, A. Storch, and Timothy J. Collier: A Clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: A source of cells for transplantation in Parkinson’s disease. Exp. Neurology 2001; 171:98-108. Ling, Z.D., D.A. Gayle, S.Y. Ma, J.W. Lipton, C.W. Tong, J.S. Hong, and P.M. Carvey. In Utero Bacterial Endotoxin Exposure Causes Loss of Tyrosine Hydroxylase Neurons in the Postnatal Rat Midbrain.. Mov. Disorders 17:(1)116-124; 2002.