Moffitt Cancer Center Logo
 

Sandy D. Westerheide, PhD

Where You Are:
Sandy D. Westerheide, PhD

Office  (813) 979-7269

Education And Training
  • PhD, Emory University, 1998 - Genetics and Molecular Biology


Research in my laboratory is directed at understanding the molecular importance of the heat shock response (HSR) in cellular metabolism, aging and disease.  The HSR is a universally conserved pathway that allows cells to recover from protein damage induced by various stressors.  The heat shock transcription factor HSF1, the master regulator of the HSR, transcriptionally activates molecular chaperones and other genes that are essential for cell survival.  We are interested in understanding how the HSR can be modulated to provide therapeutic benefit for a variety of disease states.  Upregulation of the HSR could be therapeutically beneficial in various neurodegenerative diseases.  Conversely, downregulation of the HSR could be beneficial in cancer treatment. 

 

We have recently found that HSF1 is regulated by the longevity factor SIRT1.  SIRT1 is a metabolically regulated deacetylase that is required for full HSF1 transcription. We have shown that HSF1 is acetylated within its DNA binding domain at lysine 80, and that acetylation at this site disrupts DNA binding. Deacetylation of this residue by SIRT1 maintains HSF1 in a DNA-binding competent state, activating HSF1-dependent transcription and the HSR.  We are interested in further investigating the links between the heat shock response and cell metabolism and lifespan.

 

 

  • Foley J, Hill SE, Miti T, Mulaj M, Ciesla M, Robeel R, Persichilli C, Raynes R, Westerheide S, Muschol M. Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth. J Chem Phys. 2013 Sep;139(12):121901. Pubmedid: 24089713.
  • Raynes R, Pombier KM, Nguyen K, Brunquell J, Mendez JE, Westerheide SD. The SIRT1 modulators AROS and DBC1 regulate HSF1 activity and the heat shock response. PLoS One. 2013 Jul;8(1):e54364. Pubmedid: 23349863. Pmcid: PMC3548779.
  • Raynes R, Brunquell J, Westerheide SD. Stress Inducibility of SIRT1 and Its Role in Cytoprotection and Cancer. Genes Cancer. 2013 Mar;4(3-4):172-182. Pubmedid: 24020008. Pmcid: PMC3764474.
  • Raynes R, Leckey BD, Nguyen K, Westerheide SD. Heat shock and caloric restriction have a synergistic effect on the heat shock response in a sir2.1-dependent manner in Caenorhabditis elegans. J Biol Chem. 2012 Aug;287(34):29045-29053. Pubmedid: 22778258. Pmcid: PMC3436562.
  • Westerheide SD, Raynes R, Powell C, Xue B, Uversky VN. HSF Transcription Factor Family, Heat Shock Response, and Protein Intrinsic Disorder. Curr Protein Pept Sci. 2012 Feb;13(1):86-103. Pubmedid: 22044151.
  • Wang D, Westerheide SD, Hanson JL, Baldwin AS. Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. J Biol Chem. 2000 Oct;275(42):32592-32597. Pubmedid: 10938077.
TOOLS:   Font Size small font resizer separator font resizer separator big font resizer