Mary R. Loeken, PhD
Associate Professor, Department of Medicine, Harvard Medical School
Investigator, Section on Islet and Regenerative Cell Biology, Joslin Diabetes Center
DF/HCC Program AffiliationNeuro-Oncology
Lab WebsiteJoslin Loeken Lab
We are interested in the role of the Pax-3 transcription factor in neuroepithelial/neural crest development. This research initiated in an effort to understand the causes of neural tube and cardiac neural crest defects in the offspring of mothers with diabetes. Using a mouse model of diabetic pregnancy, we found that expression of Pax-3 is significantly impaired, and consequently, Pax-3-deficient cells undergo apoptosis. We recently found that Pax-3 down regulates p53 protein (either by inhibiting protein translation or stability), thereby suppressing p53-dependent apoptosis. While suppression of p53-dependent apoptosis by Pax-3 may be a necessary process during neuroepithelial/neural crest development, this could contribute to the oncogenic process in tumors derived from PAX-3-expressing tissues (such as neuroblastoma, Ewing's sarcoma, melanoma, and pediatric rhabdomyosarcoma), in which PAX-3 re-emerges. We have two areas of research related to the mission of DF/HCC: (a) to investigate the role of Pax-3 suppression of p53-dependent cell cycle withdrawal or apoptosis on neuroepithelial and neural crest cell fate; (b) to establish new embryonic cell lines derived from embryos carrying wild type or mutant Pax-3 alleles in various combination with wild type or mutant p53 alleles.
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