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Gail V W Johnson, Ph.D.

Contact Information

Phone Numbers

Office: (585) 276-3740

Research Labs

The Johnson Lab

Lab: (585) 276-4005

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Faculty Appointments

Biography

Research

THE MOLECULAR MECHANISMS OF NEURODEGENERATION
gail_johnsonvoll@urmc.rochester.edu
Our laboratory has a longstanding interest in the pathogenic processes in Alzheimer's disease (AD) and central nervous system (CNS) injury. 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. Currently studies in our lab are focused in two areas: (1) on understanding the regulation and function of the protein in tau in the context of AD, and (2) on how a protein called transglutaminase 2 (TG2) differentially impacts the survival and function of neurons and astrocytes following CNS injury. Each of these two areas of research that are ongoing in our lab is discussed briefly below.
The neuronally enriched protein tau plays a primary role in the pathogenesis of AD. Indeed, abnormal accumulations of aberrantly modified forms of the protein, neurofibrillary tangles, are one of the defining hallmarks of the disease. However, why the levels of these pathogenic forms of tau increase in AD, and how they cause toxicity are questions that have not been satisfactorily answered. A major focus of our studies involves determining how a neuron recognizes tau that is abnormally modified or no longer functional, and targets it to the autophagy pathway for degradation. In particular our group is interested in determining if a complex containing the co-chaperone BAG3 and other interacting proteins plays a role in not only directing tau to autophagy, but also in mediating the autophagy process. Further, our lab is also investigating how pathologically relevant forms of tau impact mitochondrial biology and the general health/functioning of the neuron.
Our lab also has a well-established interest in understanding the regulation and function of TG2 in neuronal cell death and survival. We have found that in neurons TG2 localizes to the nucleus in response to stress and plays a protective role. Intriguingly the converse is true for TG2 in astrocytes where it plays a detrimental role. Knockdown or deletion of TG2 from astrocytes significantly increases survival after stress and significantly increases their ability to protein neurons from insults. Given these and other findings we are currently delineating the differential roles of TG2 in regulating gene expression profiles in neurons and astrocytes. We are also examining how selective deletion of astrocytic TG2 improves outcomes after spinal cord injury, as well as investigating selective TG2 inhibitors as possible therapeutic interventions in the treatment of spinal cord injury.
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Credentials

Education

1976
B.A. | Southampton College
Biology

1978
M.S. | University of Massachusetts
Entomology

1984
Ph.D. | University of Delaware
Physiology

Post-doctoral Training & Residency

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

Awards

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

1992
Ciba Foundation Fellow Sponsor

1989 - 1994
NIH First Award

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Publications

Journal Articles

2/11/2019
Ji C, Tang M, Zeidler C, Höhfeld J, Johnson GV. "BAG3 and SYNPO (synaptopodin) facilitate phospho-MAPT/Tau degradation via autophagy in neuronal processes." Autophagy.. 2019 Feb 11; Epub 2019 Feb 11.

2/2/2019
Liu C, Luo R, Wang W, Peng Z, Johnson GVW, Kellems RE, Xia Y. "Tissue transglutaminase-mediated AT1 receptor sensitization underlies pro-inflammatory cytokine LIGHT-induced hypertension." American journal of hypertension.. 2019 Feb 2; Epub 2019 Feb 02.

1/2019
Fu H, Possenti A, Freer R, Nakano Y, Villegas NCH, Tang M, Cauhy PVM, Lassus BA, Chen S, Fowler SL, Figueroa HY, Huey ED, Johnson GVW, Vendruscolo M, Duff KE. "A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology." Nature neuroscience.. 2019 Jan 0; 22(1):47-56. Epub 2018 Dec 17.

Books & Chapters

2017
Chapter Title: Assessing the degradation of tau in primary neurons: the role of autophagy
Book Title: Methods in Cell Biology
Author List: Ji, C., Tang, M. and Johnson G.V.W.
Edited By: S. Feinstein and N. LaPointe,
Published By: Elsevier 2017 in Oxford, England

2016
Chapter Title: Stimulation of Tau Degradation
Book Title: Developing Therapeutics for Alzheimer's Disease: Progress and Challenges
Author List: Quintanilla, R.A., Cabezas-Opazo, F., Pallo, S.P., Chesser, A.S. and Johnson, G.V.W.
Edited By: Michael S. Wolfe
Published By: Elsevier Publishing 2016 in Waltham, MA.

2015
Chapter Title: Transglutaminases and Neurological Diseases
Book Title: Transglutaminases: Multiple Functional Modifiers and Targets for New Drug Discovery
Author List: Feola, J., Monteagudo, A., Yunes-Medina, L. and Johnson, G.V.W.
Edited By: Kiyotaka Hitomi, Soichi Kojima, and Laszlo Fesus
Published By: Springer Publishing 2015

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