Guilian M Xu

Guilian M Xu

Associate Scientist

Department: MD-NEUROSCIENCE-GENERAL
Business Phone: (352) 273-6667
Business Email: xugl@ufl.edu

About Guilian M Xu

My work is trying to find the underlying mechanisms of age-related brain disorders, such as Alzheimer’s disease (AD), Huntington disease (HD), Parkinson’s disease (PD) and motor neuron diseases (ALS). HD only has a familial form, while AD, PD, and ALS have both familial forms inherited from parents and sporadic forms that do not have a clear family link. Geneticists have discovered the genes that cause these diseases, and we make genetically engineered mice that modify those genes to model the conditions according to their findings. In most cases, the mice show the same symptoms as the patients. It is extremely beneficial to study the mechanisms and try therapies on the disease models of mice before translating into patients.

All these disorders seem to share similar common mechanisms of pathogenesis, although for now, no single common mechanism has yet emerged. All these diseases have insoluble protein accumulation involved and the major aggregated proteins are transmissible. I am testing a hypothesis called “secondary misfolding” by protein homeostasis damage which states: if a high level of one protein (usually with disease favored mutations) starts to lose its solubility and accumulates inside the cells, it can destroy the balance of other protein production, maintenance, and clearance. This process triggers the dysfunction of many independent biological pathways simultaneously and eventually kills the cells. This work involves the use of transgenic mouse models, human tissues, and cell culture systems to examine the soluble, insoluble proteins and their relationship with some bioinformatics tools.

Research Profile

Areas of Interest
  • ALS
  • Alzheimer’s Disease
  • Neuropathology of Neurodegenerative diseases

Publications

2020
Diversity in Aβ deposit morphology and secondary proteome insolubility across models of Alzheimer-type amyloidosis.
Acta neuropathologica communications. 8(1) [DOI] 10.1186/s40478-020-00911-y. [PMID] 32252825.
2019
Aberrant accrual of BIN1 near Alzheimer’s disease amyloid deposits in transgenic models.
Brain pathology (Zurich, Switzerland). 29(4):485-501 [DOI] 10.1111/bpa.12687. [PMID] 30506549.
2018
Changes in proteome solubility indicate widespread proteostatic disruption in mouse models of neurodegenerative disease.
Acta neuropathologica. 136(6):919-938 [DOI] 10.1007/s00401-018-1895-y. [PMID] 30140941.
2018
Characterization of gene regulation and protein interaction networks for Matrin 3 encoding mutations linked to amyotrophic lateral sclerosis and myopathy.
Scientific reports. 8(1) [DOI] 10.1038/s41598-018-21371-4. [PMID] 29511296.
2018
Differential induction of mutant SOD1 misfolding and aggregation by tau and α-synuclein pathology.
Molecular neurodegeneration. 13(1) [DOI] 10.1186/s13024-018-0253-9. [PMID] 29776378.
2016
Vulnerability of newly synthesized proteins to proteostasis stress.
Journal of cell science. 129(9):1892-901 [DOI] 10.1242/jcs.176479. [PMID] 27026526.
2015
Murine a Beta Over-Production Produces Diffuse and Compact Alzheimer-Type Amyloid Deposits
Acta Neuropathologica Communications. 3 [DOI] 10.1186/s40478-015-0252-9. [PMID] 26566997.
2015
Substantially elevating the levels of αB-crystallin in spinal motor neurons of mutant SOD1 mice does not significantly delay paralysis or attenuate mutant protein aggregation.
Journal of neurochemistry. 133(3):452-64 [DOI] 10.1111/jnc.13022. [PMID] 25557022.
2014
Experimental Transmissibility of Mutant Sod1 Motor Neuron Disease
Acta Neuropathologica. 128(6):791-803 [DOI] 10.1007/s00401-014-1342-7. [PMID] 25262000.
2013
Comment on “ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models”.
Science (New York, N.Y.). 340(6135):924-d [DOI] 10.1126/science.1234089. [PMID] 23704553.
2013
Cytosolic proteins lose solubility as amyloid deposits in a transgenic mouse model of Alzheimer-type amyloidosis.
Human molecular genetics. 22(14):2765-74 [DOI] 10.1093/hmg/ddt121. [PMID] 23512986.
2013
Reversible Pathologic and Cognitive Phenotypes in An Inducible Model of Alzheimer-Amyloidosis
The Journal of Neuroscience. 33(9):3765-3779 [DOI] 10.1523/JNEUROSCI.4251-12.2013. [PMID] 23447589.
2012
Reduction of low-density lipoprotein receptor-related protein (LRP1) in hippocampal neurons does not proportionately reduce, or otherwise alter, amyloid deposition in APPswe/PS1dE9 transgenic mice.
Alzheimer's research & therapy. 4(2) [DOI] 10.1186/alzrt110. [PMID] 22537779.
2012
Identification of proteins sensitive to thermal stress in human neuroblastoma and glioma cell lines.
PloS one. 7(11) [DOI] 10.1371/journal.pone.0049021. [PMID] 23145051.
2011
Transgenic Mice Expressing Caspase-6-Derived N-Terminal Fragments of Mutant Huntingtin Develop Neurologic Abnormalities With Predominant Cytoplasmic Inclusion Pathology Composed Largely of a Smaller Proteolytic Derivative
Human Molecular Genetics. 20(14):2770-2782 [DOI] 10.1093/hmg/ddr176. [PMID] 21515588.
2010
Lactic Acid Induces Aberrant Amyloid Precursor Protein Processing By Promoting Its Interaction With Endoplasmic Reticulum Chaperone Proteins
PLoS One. 5(11) [DOI] 10.1371/journal.pone.0013820. [PMID] 21072203.
2009
Amyloid Precursor Protein Increases Cortical Neuron Size in Transgenic Mice
Neurobiology of Aging. 30(8):1238-1244 [DOI] 10.1016/j.neurobiolaging.2007.12.024. [PMID] 18304698.
2008
Receptor-Associated Protein (Rap) Plays a Central Role in Modulating a Beta Deposition in App/Ps1 Transgenic Mice
PLoS One. 3(9) [DOI] 10.1371/journal.pone.0003159. [PMID] 18776935.
2007
Alzheimer’s-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 27(25):6771-80 [PMID] 17581964.
View on: PubMed
2005
Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer’s disease.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 25(21):5217-24 [PMID] 15917461.
View on: PubMed
2005
Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer’s disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities.
Neurobiology of disease. 18(3):602-17 [PMID] 15755686.
View on: PubMed
2004
Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase.
Human molecular genetics. 13(2):159-70 [PMID] 14645205.
View on: PubMed
2003
Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APP SWE.
Neurobiology of disease. 12(3):194-211 [PMID] 12742740.
View on: PubMed

Grants

Feb 2018 – Feb 2020
Seeded interactions of A? and neurofibrillary tangle pathologies in mouse models
Role: Principal Investigator
Funding: FL DEPT OF HLTH ED ETHEL MOORE ALZHEIMER
Jul 2014 – Jun 2018
Protein homeostasis in mouse models of Alzheimer pathology
Role: Principal Investigator
Funding: BRIGHTFOCUS FOU

Education

M.S. (ISOM on Data Science)
2017 · University of Florida
Ph.D. (Physiology)
2001 · University of Hong Kong
B.S. (Biochemistry)
1991 · Sichuan University

Contact Details

Phones:
Business:
(352) 273-6667
Emails:
Business:
xugl@ufl.edu