Email: physiology@rosalindfranklin.edu Fax: 847.578.3265
Hawkins, Richard A Kim, Donghee
Najmabadi, Feridoon McCormack, Charles E. Peterson, Darryl R. Rasgado-Flores, Hèctor
Current studies in my laboratory focus on transport properties of the blood-brain barrier, and its role in regulating brain extracellular fluid. The blood-brain barrier is formed by endothelial cells that line cerebral capillaries. These cells possess true tight junctions that polarize the endothelium into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains, imparting a high electrical resistance. Thus, solutes must cross the blood-brain barrier primarily by crossing the limiting plasma membranes. We are interested in defining specific transport systems in each of these membrane domains, as a basis for modeling transport pathways across the blood-brain barrier. Emphasis is on: 1) nutrient delivery to the brain; 2) fluid and electrolyte transport; and 3) access of therapeutic agents to the central nervous system. Transport mechanisms are characterized directly in isolated plasma membrane vesicles, derived by fractionating cerebral capillary endothelial cells. Studies are also performed using isolated capillary fragments, brain capillary endothelial cells in culture, and in intact animals. Thus, a multi-faceted approach is employed involving molecular, cellular, and whole animal methodologies. These studies are pertinent to normal regulatory functions of the blood-brain barrier, the pathophysiology of stroke, and the delivery of therapeutic drugs to the central nervous system for the treatment of neurological disorders. We are also currently investigating the development of therapeutic agents for cytoprotection of selected tissues under toxic conditions, including the blood-brain barrier and kidneys.
Recent Publications (selected):
Lee, W-J. R.A. Hawkins, J.R. Viña, and D.R. Peterson. Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal. Am. J. Physiol. 274: C1101-C1107, 1998.
Peterson, D.R. and R.A. Hawkins. Isolation and behavior of plasma membrane vesicles made from cerebral capillary endothelial cells. In: An Introduction to the Blood-Brain barrier: Methodology and Biology. Ed., W. Pardridge. Cambridge University Press, pp. 62-70, 1998.
Wallner, E.I., Q.Yang, D.R. Peterson, J. Wada, Y.S. Kanwar. Relevance of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis. Am. J. Physiol. 275: F467-F477, 1998.
Y.S. Kanwar, K. Ota, Q. Yang, A. Kumar, J. Wada, N. Kashihara, and D.R. Peterson. Isoaltion of rat fibrillin-1 cDNA and its relevance in metanephric development. Am. J. Physiol. 275: F710-F723, 1998.
Yang, Q., Y. Tian, J. Wada, N. Kashihara, E.I. Wallner, D.R. Peterson and Y. Kanwar. Expression characteristics and relevance of sodium glucose co-transporter (SGLT-1) to tubulogenesis in metanephric development. Am. J. Physiol. 279: F765-F777, 2000.
Peterson, D.R. and R.A. Hawkins. Transport studies using membrane vesicles. In: Blood-Brain Barrier: Biology and Protocols. Humana Press, Inc. Totowa. Pp, 233-247, 2003.
Neuwelt, E.A., M.A. Pagel, D.F. Kraemer, D.R. Peterson, and L.L. Muldoon. Bone marrow chemoprotection without compromise of chemotherapy efficacy in rat brain tumor model. J. Pharmacol. Exp. Ther. 309: 1-6, 2004.
Peterson, D.R. Blood-brain barrier. In: Encyclopedia of Life Sciences. Macmillan Reference Ltd., London, 2005.
Riser, B.L., S. Karoor, and D.R. Peterson. CCN genes and the kidney. In CCN proteins: a new family of cell growth and differentiation regulators. B. Perbal and M. Takigawa, eds. Imperial College Press, UK, pp. 95-116, 2005.
Cooker, L., D.R. Peterson, J. Rambow, M. Riser, R. Riser, F. Najmabadi, D. Brigstock, and B. Riser. TNF-alpha, but not IFN-gamma, regulates CCN2 (CTGF), collagen type I, and proliferation in mesangial cells: possible roles in the progression of renal fibrosis. Am. J. Physiol. F157-F165, 2007.
Dickey, D.T., L. L. Muldoon, N.D. Doolittle, D. R. Peterson, D.F. Kraemer, and E. A. Neuwelt. Effect of N-acetylcysteine route of administration on chemoprotection against cisplatin-induced nephrotoxicity in rat models. Cancer Chemother. Pharmacol. In press.
Stenstrom, D.A., L.L. Muldoon, H. Armijo-Medina, S. Watnick, N. D. Doolittle, J. A. Kaufman, D.R. Peterson, J. Bubalo, and E.A. Neuwelt. Can N-acetylcysteine prevent contrast induced nephropathy: Premature phase III trials. J. Vasc. Interven. Radiol. In press.