Gail V.W. Johnson

Professor of Psychiatry

1061 Sparks Center

University of Alabama at Birmingham School of Medicine

Birmingham, AL 35294-0017

 gvwj@uab.edu

Gail V. W. Johnson (b. 1955) Professor of Psychiatry, Cell Biology and Neurobiology, received her B.A. degree in biology from Southampton College (1976), her M.S. degree in entomology from the University of Massachusetts (1978) and a Ph.D. degree (1984) in physiology from the University of Delaware. Postdoctoral studies were pursued at UAB prior to joining the faculty in 1990. Dr. Johnson holds joint appointments in the departments of Cell Biology, Neurobiology and Pharmacology. Her laboratory is well-funded and productive, and many of her former graduate students and postdoctoral fellows have gone on to successful careers in science.  In addition to her research endeavors, Dr. Johnson is a dedicated runner.

The Microtubule-Associated Protein Tau

A primary focus of our laboratory is on the function and dysfunction of the neuronal cytoskeletal phosphoprotein tau. Tau is a microtubule-associated protein, and in this capacity stabilizes microtubules and promotes microtubule assembly. However, tau also plays a role in neurite outgrowth independent of its ability to bind to microtubules, and there is evidence to suggest that tau is involved in modulating signal transduction pathways. Considering these and other findings, it is clear that tau is likely to play a central role in neuronal cell function. In addition, abnormally hyperphosphorylated tau aggregates and forms pathological intracellular inclusions called neurofibrillary tangles in Alzheimer's disease brain. Further, mutations in the tau gene have been shown to cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17).  In FTDP-17 there is extensive neuronal loss in the frontal and temporal cerebral cortex, and also an abnormal accumulation of hyperphosphorylated tau.   Currently our laboratory is investigating several aspects of tau protein metabolism and function as they relate to both normal and pathological conditions. These investigations include: (1) defining factors which modulate the localization of tau within the cell, (2) identifying the signaling pathways and specific protein kinases that modulate tau phosphorylation, (3) determining how specific FTDP-17 mutations affect tau phosphorylation, function and  localization, and (4) determining the relationship between apoptosis and tau phosphorylation. These studies will help elucidate the normal metabolism and function of tau protein and increase our understanding of the role of tau in the pathogenesis of Alzheimer's disease and FTDP-17.

Transglutaminase and Huntington's Disease

A second focus of our laboratory is on the enzyme tissue transglutaminase.  This enzyme catalyzes the formation of an isopeptide bond between a polypeptide bound glutamine and a polypeptide bound lysine, or the incorporation of a polyamine into the polypeptide bound glutamine.  Huntington's disease is caused by an unstable expansion of a polyglutamine stretch in a protein called huntingtin.  Because a polypeptide bound glutamine is the primary determining factor for a transglutaminase substrate, it had been hypothesized that tissue transglutaminase may be involved the pathogenesis of Huntington's disease by abnormally modifying mutant huntingtin.  Indeed, our laboratory recently demonstrated that the levels and activity of tissue transglutaminase are elevated in Huntington's disease brain in a grade and region dependent manner. Nonetheless, we recently demonstrated that in the cell huntingtin is not a substrate of tissue transglutaminase, however proteins that selectively associate with mutant huntingtin are modified by tissue transglutaminase. Therefore we are: (1) investigating the mechanisms that regulate tissue transglutaminase expression and activity, and (2) identifying the proteins that are selective substrates of tissue transglutaminase and determine how modification by tissue transglutaminase affects their function, (3) determining how tissue transglutaminase may regulate transcriptional events, and (4) elucidating the role of tissue transglutaminase in modulating neurite outgrowth.

Recent Publications (Representative): .

 


 And Links to photos of the lab:

RG