JOHN E. GREENLEE
Professor of Neurology
Neurologist, Veterans Administration Hospital
Neurobiology of Disease
Remote effects of cancer on the nervous system
Viral infections of the nervous system
Dr. Greenlee's laboratory investigates the role of the immune system in paraneoplastic cerebellar degeneration, a nonmetastatic complication of systemic cancer, characterized by destruction of cerebellar Purkinje cells and at times other neurons. The condition occurs most often in the setting of cancer of the lung, cancer of the female reproductive tract, or cancer of the breast. The onset of symptoms may be as long as two years before detection of the associated neoplasm. Dr. Greenlee's laboratory has shown that sera and cerebrospinal fluid from patients with this disorder contain high titers of antibodies to Purkinje cells and other target populations of neurons. Work over the past several years has demonstrated that this antibody response is elicited by tumor proteins similar to antigens within Purkinje cells or other neurons. Our recent investigations, employing organotypic cultures of rat cerebellum, demonstrate that these antibodies can be taken up by neurons and produce neuronal death. We are currently studying mechanisms of antibody uptake by neurons and mechanisms involved in antibody-mediated cell death.
O'Neill, F.J., Greenlee, J.E., Dörries, K., Clawson, S.A. and Carney, H. (2003) Propagation of archetype and non-archetype JC virus variants in human fetal brain cultures: Demonstration of interference activity by archetype JCV. J Neurovirol., 9:567-576.
Greenlee, J.E., Steffens, J.D., Clawson, S.A., Hill, K., and Dalmau, J. (2002) Anti-Hu antibodies in Merkel Cell Carcinoma. Annals of Neurology, 52:111-115.
Greenlee, J.E., Boyden, J.W., Pingree, M., Brashear, H.R., Clawson, S.A., and Keeney, P.M. (2001) Antibody types and IgG subclasses in paraneoplastic neurological syndromes. J Neurol Sci, 184:131-137.
Greenlee, J.E., Dalmau, J., Lyons, T., Clawson, S.A., Smith, R.H., and Pirch, H.R. (1999) Association of anti-Yo (type I) antibodies with paraneoplastic cerebellar degeneration in the setting of transitional cell carcinoma of the bladder: detection of Yo antigen in tumor tissue and fall in antibody titers following tumor removal. Annals of Neurology 45:805-809.
Greenlee, J.E., Burns, J.B., Rose, J.W., Jaeckle, K.A., and Clawson, C. (1995) Systemically administered Type I ("Anti-Yo") IgG, associated with paraneoplastic cerebellar degeneration, is taken up by rat Purkinje cells in vivo. Acta Neuropathologica 36:342-345.
Moll, J.W.B., Antoine, J.C., Brashear, H.R., Delattre, J., Drlicek, M., Giometto, B., Graus, F., Greenlee, J., Honnorat, J., Jaeckle, K.A., Tanaka, K., and Vecht, ChJ. (1995) Guidelines on the detection of paraneoplastic anti-neuronal specific antibodies. Neurology 45:1937-1941.
Greenlee, J.E., Parks, T.N., and Jaeckle, K.A. (1993) Type IIA ("Anti-Hu") antibodies, associated with human paraneoplastic syndromes, are taken up by and produce destruction of cultured rat granule cell neurons. Neurology 43:2049-2054.
Sakai, K., Ogasawara, T., Hirose, G., Jaeckle, K.A., and Greenlee, J.E. (1993) Analysis of autoantibody binding to 52 kd paraneoplastic cerebellar degeneration-associated antigen expressed in recombinant proteins. Ann. Neurol. 33:373-380.