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 (by stimulating Mdm2-mediated ubiquitination), 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 study 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 with which to study regulation of metabolism in embryonic cells, effects on Pax3 expression, and effects of Pax3 on p53 stability, proliferation, and differentiation.
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