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Gail V W Johnson, Ph.D.

Contact Information

Phone Numbers

Office: (585) 276-3740

Fax: (585) 276-2418

Faculty Appointments




Our laboratory has a longstanding interest in the pathogenic processes in Alzheimer disease and Huntington disease, and more recently in stroke. For our studies we use a wide variety of different approaches from in vitro enzyme assays with purified proteins, to studies in whole animals. This broad-based approach allows us to translate what we learn about a process or signaling pathway at the molecular level to the in vivo situation. Each of the 3 areas of research that are ongoing in our lab is discussed briefly below.
Two hallmarks of the Alzheimer's disease brain are the intracellular neurofibrillary tangles composed primarily of the protein tau in a pathologically modified state and the extracellular senile plaques composed primarily of the Abeta peptide. There is compelling evidence that aberrant posttranslational processing of tau is central to the disease process. Nonetheless, the mechanisms by which pathological changes in tau result in impaired neuronal function and contribute to cell death processes in Alzheimer disease have not been fully elucidated. A major focus in our lab is on understanding the cellular targets of Alzheimer disease relevant forms of tau. Currently we are investigating how tau that is abnormally phosphorylated and/or proteolytically processed impacts mitochondrial dynamics and function. We and others have exciting new data suggesting that the mitochondria may be a crucial downstream target of pathological tau and contribute to the neurodegenerative processes.
Our lab has a well-established and longstanding interest in understanding the regulation and function of transglutaminase 2 (TG2) in neuronal cell death and survival. Recently we found that TG2 in its capacity as a scaffold protein binds HIF1beta, attenuates HIF signaling, attenuates the expression of specific HIF responsive pro-apoptotic genes and protects neurons from ischemia-induced cell death. In addition, we have found that exogenous expression of TG2 in neurons in a mouse is protective against stroke damage. Therefore we are investigating the mechanisms by which TG2 attenuates HIF signaling and protects against ischemia-induced cell death.

Huntington disease is an autosomal dominant neurodegenerative disease caused by a pathological expansion of the polyglutamine domain in the huntingtin protein. There is convincing evidence that both transcriptional dysregulation and mitochondrial dysfunction play pivotal roles in the pathogenesis of Huntington disease. In recent studies we have found that mitochondria from mutant huntingtin expressing striatal cells take up significantly less calcium than mitochondria from wild type cells and are significantly more sensitive to calcium-induced decreases in respiration. We have also found that the expression of specific mitochondrial and anti-oxidant genes are downregulated in Huntington disease cell models. Therefore we are now investigating: (1) whether mutant huntingtin impairs the ability of mitochondria to appropriately maintain pH and regulate redox status and if this contributes to the calcium handling defects that result in respiratory deficits and increased sensitivity to calcium-induced permeability transition pore opening, (2) whether a decrease in the transcriptional activity PPARgamma by mutant huntingtin compromises mitochondrial metabolism and function and (3) whether activation of PPARgamma ameliorates mitochondrial dysfunction in mouse Huntington's disease models.



B.A. | Southampton College

M.S. | University of Massachusetts

Ph.D. | University of Delaware

Post-doctoral Training & Residency

1985 - 1988
Postdoctoral Research Fellow, Department of Pharmacology, University of Alabama at Birmingham (UAB), Birmingham, AL


1994 - 1996
Ruth K. Broad Biomedical Research Foundation, Inc. Awardee

Ciba Foundation Fellow Sponsor

1989 - 1994
NIH First Award

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Journal Articles

Quintanilla, R.A., Matthews-Roberson, T.A., Dolan, P.J. and Johnson, G.V.W. "Caspase-cleaved tau expression results in mitochondrial dysfunction in cortical neurons. Implications for the pathogenesis of Alzheimer disease". Journal of Biological Chemistry. 2009; 284: 18754-18766.

Beagle, B.B., Mi, K. and Johnson, G.V.W. "Phosphorylation of PPP(S/T)P motif in non-membrane anchored LRP6 intracellular domain is not required to activate the Wnt/beta-Catenin pathway and attenuate GSK3beta activity". Journal of Cellular Biochemistry. 2009; 108: 886-895.

Quintanilla, R.A. and Johnson, G.V.W. "The role of mitochondrial dysfunction in Huntington disease". Brain Research Bulletin. 2009; 80: 242-247.

Books & Chapters

Chapter Title: Transglutaminases in neurodegenerative disorders
Book Title: Transglutaminases: the family of enzymes with diverse functions Progress in Expe
Author List: Bailey, CDC; Tucholski, J; Johnson, GVW
Edited By: K. Mehta and R. Eckert
Published By: Karger Publishers2005

Chapter Title: "Measurement of calpain activity in vitro and in situ using a fluorescent compound and tau protein as substrates".
Book Title: Calpain Methods & Protocols: Methods in Molecular Biology
Author List: Guttmann, RP; Johnson, GVW
Published By: Calpain Methods & Protocols: Methods in Molecular Biology1999

Chapter Title: Calpain-mediated proteolysis of neuronal structural proteins
Book Title: The Pharmacology and Toxicology of Calpain
Author List: Guttmann, RP; Johnson, GVW
Edited By: K.K.W. Wang and P. Yuen
Published By: Taylor and Francis Publishers1999 in NY