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Dr. Guilian Xu

Dr. Guilian Xu

Research Assistant Scientist, Neuroscience
Member, CTRND
Post Doc, Neuropatholgy, Johns Hopkins University, 2001-2005
Ph.D., Physiology, The University of Hong Kong, 2001
B.S., Biochemistry, Sichuan University, China 1991




Contact Dr. Xu
Office: 352-273-6667
Lab: 352-294-5159

Research Focus and Aims

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.

Current Research Projects

Protein homeostasis study of AD, PD, HD and ALS transgenic mouse models

Selected Publications


  1. Xu G, Pattamata A, Hildago R, Pace MC, Brown H, and Borchelt DR. Vulnerability of newly synthesized proteins to proteostasis stress. Journal of Cell Science. 129(9):1892-1901. (2016)
  2. Xu G, Fromholt S, Ayers JI, Brown H, Siemienski Z, Crosby KW, Ayer CA, Janus C, and Borchelt DR..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. J Neurochem. 133(3): 452-464. (2015)
  3. Xu G, Ran Y, Fromholt SE, Fu C, Yachnis AT, Golde TE, and Borchelt DR. Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits. Acta Neuropathol Commun. 3(1): 72. (2015)
  4. Xu G, Ayers JI, Roberts BL, Brown H, Fromholt S, Green C, and Borchelt DR. Direct and indirect mechanisms for wild-type SOD1 to enhance the toxicity of mutant SOD1 in bigenic transgenic mice. Hum Mol Genet. 24(4): 1019-1035. (2015)
  5. Price AR*, Xu G*, Siemienski ZB, Smithson LA, Borchelt DR, Golde TE, and Felsenstein KM. Comment on “ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models”. Science. 340(6135): 924-924d. (2013)   –equal contribution
  6. Xu G, Stevens SM Jr, Moore BD, McClung S, and Borchelt DR. Cytosolic proteins lose solubility as amyloid deposits in a transgenic mouse model of Alzheimer-type amyloidosis. Hum Mol Genet. 22(14): 2765-2774. (2013)
  7. Xu G, Green CC, Fromholt SE, and Borchelt DR. 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. Alzheimers Res Ther. 4(2): 12. (2012)
  8. Xu G, Stevens SM Jr, Kobeissy F, Brown H, McClung S, Gold MS, and Borchelt DR. Identification of proteins sensitive to thermal stress in human neuroblastoma and glioma cell lines. PLoS One. 7(11): e49021. (2012)
  9. Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Younkin LH, Younkin SG, Borchelt DR, and Savonenko AV. Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer’s disease. J. Neurosci. 25: 5217-5224. (2005)
  10. Wang J, Xu G, Li H, Gonzales V, Fromholt D, Karch C, Copeland NG, Jenkins NA, Borchelt DR. Somatodendritic accumulation of misfolded SOD1-L126Z in motor neurons mediates degeneration: alphaB-crystallin modulates aggregation. Hum Mol Genet. 14(16):2335-47. (2005)
  11. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR.  Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: Evidence for augmentation of a 42-specific gamma-secretase.  Hum. Mol. Gen. 13:159-170, (2004).
  12. Xu G, Gonzales V, Borchelt DR. Abeta deposition does not cause the aggregation of endogenous tau in transgenic mice. Alzheimer Dis Assoc Disord. 16(3):196-201. (2002)
  13. Xu G, Gonzales V, Borchelt DR. Rapid detection of protein aggregates in the brains of Alzheimer patients and transgenic mouse models of amyloidosis. Alzheimer Dis Assoc Disord. 16(3):191-5. (2002)
  14. Lesuisse C, Xu G, Anderson J, Wong M, Jankowsky J, Holtz G, Gonzalez V, Wong PC, Price DL, Tang F, Wagner S, Borchelt DR. Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice. Hum Mol Genet. 10(22):2525-37. (2001)
  15. Tang F, Li H, Nag S, Xu G, Chan T. Transgenic mouse and chemical lesion approaches to the study of Alzheimer’s disease. Chin Med J (Engl). 110(8):642-7. Review. (1997)


Link To PubMed