Adaptations to Changes in Oxygen Availability
Celeste Simon, Ph.D.,
Professor, Cell and Developmental Biology
University of Pennsylvania
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Abstract: During the past century it has been established that regions within solid tumours experience mild to severe O2 deprivation owing to aberrant vascular function. These hypoxic regions are associated with altered cellular metabolism, as well as increased resistance to radiation and chemotherapy. Over the past decade, work from many laboratories has elucidated the mechanisms by which hypoxia-inducible factors (HIFs) modulate tumour cell metabolism, angiogenesis, growth, and metastasis. The central role played by intra-tumoural hypoxia and HIF in these processes has made them attractive therapeutic targets in the treatment of multiple human malignancies.
Presenter Biography: Dr. Simon obtained a bachelor’s degree at Miami University (Oxford, Ohio) in 1977, and an M.S. in Microbiology at Ohio State University in 1980. Her Ph.D. in Biochemistry was obtained from Rockefeller University in 1985. She conducted postdoctoral research in the laboratories of Dr. Joseph Nevins (Rockefeller University) and Dr. Stuart Orkin (Harvard Medical School). As a Howard Hughes Associate in Dr. Orkin’s laboratory, she began her work on hematopoietic development using mouse embryonic stem cells as a model for differentiation.
Her first faculty position was at the University of Chicago (1992), Department of Medicine, where she continued her studies on hematopoiesis. She became an assistant investigator of the Howard Hughes Medical Institute in 1994 in a national competition that appointed seventeen junior faculty to the HHMI. Focusing on the role of the PU.1 transcription factor in specifying hematopoietic cell fate, Dr. Simon definitively showed that PU.1 is essential for the development of macrophages, neutrophils, B lymphocytes, T lymphocytes, and mast cells. At this time, she developed an interest in angiogenesis and how hematopoiesis and angiogenesis are tightly linked in the developing mouse embryo. She turned her attention to the role of oxygen (O2) availability in regulating hematopoiesis and angiogenesis and studied mouse knockouts of the hypoxia inducible factor (HIF) signaling pathways. These studies show that the naturally low O2 environment of the developing embryo regulates blood cell, blood vessel, placental, and cardiac development via HIF. In 1999, she joined the new Abramson Family Cancer Research Institute (AFCRI) at the University of Pennsylvania School of Medicine and is now a Professor there. She was promoted to Associate Investigator (HHMI) in 2000, and full Investigator in 2005. On September 1, 2007, she became the Scientific Director of the AFCRI.
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