People
William D. Hobey
Professor Emeritus
Faculty Listing
Fax: +1-508-831-5933
whobey@wpi.edu
Educational Background
- B.S., Tufts Univ., 1957
- Ph.D., California Institute of Technology, 1962
Research
My research focuses on how phosphorylation modulates the transport of ions through biological membranes. The lipid bilayer of the membrane presents a dielectric barrier to the passage of ions which nature circumvents by a complex of protein molecules penetrating the bilayer. Frequently, this structure is “gated”, i. e. it can be opened and closed under the action of signals such as chemical messengers, changes in membrane potential for ion channels, or stress on the cell. In some cases auxiliary cytosolic proteins control or regulate the gating. The activity of the transporter may be modulated by phosphorylation of the transport protein itself or of a regulatory protein. The extent of phosphorylation is maintained through a dynamic balance between phosphorylation by a kinase utilizing ATP and dephosphorylation through the action of a phosphatase. Currently, we are working on two distinct systems, both of which are activated above normal levels by drugs.
- Red blood cell membranes contain an electrically neutral potassium/chloride cotransport system found in a variety of cell types to be involved in cell volume regulation. It is believed that the response to cell volume change is mediated through change in the activity of a protein kinase. In human erythrocytes this system shows low activity under normal physiological conditions, but can be activated under a variety of chemical procedures. It is constitutively activated in Hereditary Xerocytosis, a human hemolytic anemia. The beta-adrenergic blocker, propranolol, to a small extent by itself, and to a much larger extent in the presence of calcium ion, elicits flux of potassium ion from human red cells. We have shown that this efflux is through the cotransport system. Here we have, for the most part, taken an indirect, kinetics based approach to characterizing the mechanisms. In the process, we have developed a computerized method using ion selective electrodes for monitoring potassium fluxes from cell suspensions. We have used this methodology to characterize the propranolol binding sites, as well as the dependency of the activated cotransport on various ions and on ATP. We are currently using it to determine the dependence of the activation on phosphorylation by a number of different kinases.
- In collaboration with the laboratory of Dr. Steven Treistman at the Brudnick Neuropsychiatric Research Institute we are studying the modulation of the large conductance, calcium activated potassium (BK) channel by phosphorylation. Ethanol potentiates this channel leading to a membrane potential change that reduces the release of vasopressin from the pituitary gland. However, this release exhibits acute and chronic tolerance to the drug, which may correlate with the general tolerance to ethanol developed in alcoholism. We are investigating both whether ethanol alters the phosphorylation of BK, and whether deliberate alteration of phosphorylation modulates the response of BK to the drug. Projects here involve both electrophysiology, and standard methods of investigating changes in protein structure.
Years of Service at WPI
- Assistant Professor, 1963-67
- Associate Professor, 1967-