27-Oct-2003

Katherine Conant , MD Dr. Conant is an Assistant Professor of Neurology who has been a member of the faculty since 1998. Her research interests are focused primarily on the role that molecules which are traditionally associated with the immune response play in select processes of the central nervous system. Effects of proteases (serine proteases and matrix metalloproteinases) are of particular interest. Recent work has shown that matrix metalloproteinase-1 stimulates changes in intracellular cAMP as well as pertussis toxin-sensitive protein synthesis. Such effects may be secondary to activation of a CD47/integrin complex which is linked to Gi mediated signaling. Future studies will further explore signaling by proteases with the overall goal of determining whether these enzymes may affect cell and/or cell process migration not only through the degradation of extracellular matrix/tissue scaffolding, but through the stimulation of intracellular events that influence cell shape and protein synthesis. CURRENT ADDRESS The Johns Hopkins Hospital Department of Neurology Pathology 625 600 N. Wolfe Street Baltimore, MD 21231 Phone: 410-502-7589 Fax: 410-502-7609 e-mail: kconant@jhmi.edu EDUCATION & TRAINING 1983 A.B. Biochemistry, Cornell University, Ithaca, NY 1987 M.D. Boston University School of Medicine, Boston, MA 1987-1988 Intern in Internal Medicine, Boston City Hospital, Boston, MA 1988-1989 Research Fellow, Neurological Therapeutics, National Institutes of Health, Bethesda MD 1989-1992 Resident in Neurology, Georgetown University Hospital, Washington, DC 1992-1998 Research Fellow, Neurovirology, National Institutes of Health, Bethesda MD CURRENT APPOINTMENTS Assistant Professor of Neurology The Johns Hopkins University School of Medicine, Baltimore, MD CERTIFICATIONS 1994 Board Certified, American Board of Neurology and Psychiatry HONORS & AWARDS 1983 Phi Beta Kappa, Theta Chapter, NY 1987 Ciba Geigy Award for Excellence in Neuroscience 1997 National Institutes of Health Merit Award RESEARCH ACTIVITIES Current research projects include: Studies of matrix metalloproteinases (MMPs) which are focused on their potential to affect cell shape and process extension in neurons and astrocytes. Collaborative studies examining other potential downstream events and using microvascular endothelial cells of the blood brain barrier. Studies on stimuli (including drugs of abuse) and mechanisms that affect MMP release from cells of the brain parenchyma. Studies of protease activated receptor agonists, including thrombin and peptide ligands, which are focused on intracellular events in astrocytes (ie transcription factor binding). Collaborative studies relating to CD47 associated effects in neurons and astrocytes. REPRESENTATIVE PUBLICATIONS Conant K, Ma M, Nath A, and Major EO. Extracellular human immunodeficiency virus type 1 Tat protein is associated with an increase in both NF-kB binding and protein kinase C activity in primary human astrocytes. J Virol (1996) 70:1384-1389. Conant K, Garzino-Demo A, Nath A, McArthur JC, Halliday W, Power C, Gallo RC, Major EO. Induction of monocyte chemoattractant protein-1 in HIV-1 tat-stimulated astrocytes and elevation in AIDS dementia. Proc Natl Acad Sci USA 95:3117-3121, 1998. Conant K, Ahmed U, Schwartz, JP, Major EO. INF-g inhibits AP-1 binding activity in human brain derived cells through a nitric oxide dependent mechanism. J Neuroimmunol 88:39-44, 1998. Nath, A., Conant, K., Chen, P., Scott, C., and Major, E.O. Transient exposure of HIV-1 Tat protein results in cytokine production in macrophages and astrocytes: a hit and run phenomenon. J. Biol. Chem. 274:17098-17102, 1999 Conant K, McArthur JC, Griffin DE, Sjulson L, Wahl LM, Irani DN. Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with HIV dementia. Ann Neurol 46:391-398, 1999. Vos C, Sjulson L, Nath A, McArthur JC, Pardo C, Rothstein J, Conant K. Cytotoxicity by matrix metalloproteinase 1 in organotypic and dissociated neuronal cultures. Exp Neurol 163:324-330, 2000. Vos C., Gartner S., Ransohoff R.M., McArthur J.C., Wahl L., Sjulson L., Hunter E., and Conant K. Matrix metalloprotease-9 release from monocytes increases as a function of differentiation: implications for neurodegeneration and neuroinflammation. J Neuroimmunol. (2000) 109:221-227 Johnston, J.B., Zhang, K., Silva, C., Shalinsky, D.R., Conant, K., Ni W., Corbett D., Wee Yong V., and Power, C. HIV-1 Tat neurotoxicity is prevented by matrix metalloprotease inhibitors. Ann Neurol (2001) 49:230-41. Conant K, Haughey N, Nath A, St. Hillaire C, Gary DS, Pardo CA, Wahl LM, Bilak M, Milward E, and Mattson MP. MMP-1 activates a pertussis toxin-sensitive signaling pathway that stimulates the release of MMP-9. J Neurochem. (2002) 82:885-893.