Shi-Hua Li, M.D.


Office: 346

Lab: 355

Phone: 404-712-2304


Additional Contact Information

Mailing Address:

Whitehead Biomedical Research Building

615 Michael St.

Atlanta, GA 30322

Additional Websites

Research Interests

Nine inherited neurodegenerative disorders are caused by an expansion of a polyglutamine tract in the associated disease proteins. Of these diseases, Huntington disease (HD) has been well studied and shows altered gene expression that contributes to the disease process. Increased evidence indicates that the disease protein, huntingtin, accumulates in the nucleus and interacts with transcription factors. We found that mutant huntingtin, which contains an expanded polyglutamine tract in its N-terminal region, binds to the transcription factor Sp1 and affects Sp1-mediated gene expression. Since mutant huntingtin also forms nuclear aggregates or inclusions in the brain, it is interesting to know whether aggregated or soluble mutant huntingtin affects gene expression. Elucidating the mechanism by which mutant huntingtin affects gene expression will also provide insight into the mechanisms of other polyglutamine disorders. We hypothesize that soluble polyglutamine proteins interfere with gene expression by altering the interactions between transcription factors and their DNA targets before the formation of large nuclear inclusions. Our study is currently focusing on the questions of how mutant N-terminal huntingtin abnormally binds to transcription factors to affect gene expression and whether the altered gene expression is associated with disease progression. We will use molecular biology and HD transgenic mouse models to address these important issues. These studies will also help identify a therapeutic target for the treatment of HD and other polyglutamine diseases.

Areas of Specialization

  • Trinucleotide expansion and Neurodegenerative disease


  • MD, Medicine, Jiangxi Medical College, PR College,1977-1982