Philadelphia University + Thomas Jefferson University

Xia, Xugang

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Xugang Xia, PhD

Contact Dr. Xia

900 Walnut Street
Philadelphia, PA 19107

Research and Clinical Interests

Neurobiology of Disease

My research focuses on the mechanisms by which dopaminergic neurons selectively degenerate in Parkinson's disease (PD). PD primarily results from a substantial and progressive loss of dopaminergic neurons in the midbrain. At present, the neurons at risk cannot be protected and the disease progression cannot be prevented by any treatments available because we have a very limited understanding on the disease mechanisms. Recent advance in genetic and epidemiological study suggests a multifactorial etiology for PD. As a multifactorial disease, PD may be caused by harmful interaction between environmental toxins and genetic factors during the aging process. We have created genetically mutated animals that overexpress the disease-linked genes or are depleted of neuroprotective genes. With these genetic models, we are studying how dopaminergic neurons degenerate in the presence and in the absence of environmental toxicants.

Our laboratory uses multidisciplinary approaches to study the disease mechanisms. In collaboration with the transgenic core directed by Dr. Carlisle Landel, we have developed a technique to produce transgenic rats by pronuclear injection. Traditional gene knockout, transgenic RNAi knockdown, and transgenic gene overexpression are routinely used to produce transgenic animals in our lab. To analyze the animal models, we use histological (fluorescence and electron microscopy), biochemical (proteomics), molecular (Southern and Northern blotting, and DNA and miRNA microarray), and electrochemical (in vivo microdialysis coupled with HPLC, and cyclic voltammetry) approaches.

By a better understanding on the disease mechanisms, the pace to find a cure for PD would be accelerated.


Most Recent Peer-Reviewed Publications

  1. Increased Ubqln2 expression causes neuron death in transgenic rats
  2. Survival and cause of death among a cohort of confirmed amyotrophic lateral sclerosis cases
  3. Cytosolic PINK1 escapes from mitochondria to promote dendritic outgrowth.
  4. Profiling the genes affected by pathogenic TDP-43 in astrocytes
  5. Pathogenic Ubqln2 gains toxic properties to induce neuron death
  6. Expression of ALS-linked TDP-43 mutant in astrocytes causes non-cell-autonomous motor neuron death in rats
  7. Reactive astrocytes secrete lcn2 to promote neuron death
  8. Entorhinal cortical neurons are the primary targets of FUS mislocalization and ubiquitin aggregation in FUS transgenic rats
  9. Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats
  10. FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration
  11. Early exposure to paraquat sensitizes dopaminergic neurons to subsequent silencing of PINK1 gene expression in mice
  12. TDP-43 potentiates alpha-synuclein toxicity to dopaminergic neurons in transgenic mice
  13. Temporal expression of mutant LRRK2 in adult rats impairs dopamine reuptake
  14. Transgenic rat model of neurodegeneration caused by mutation in the TDP gene
  15. Nerve injection of viral vectors efficiently transfers transgenes into motor neurons and delivers RNAi therapy against ALS
  16. Developing tTA transgenic rats for inducible and reversible gene expression
  17. A tightly regulated Pol III promoter for synthesis of miRNA genes in tandem
  18. A construct with fluorescent indicators for conditional expression of miRNA
  19. Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression
  20. Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo