THE SIMON LABORATORY
The laboratory of M. Celeste Simon, Ph.D., has conclusively shown that a protein complex called Hypoxia Inducible Factor (HIF) regulates how a cell adapts to oxygen deprivation. Simon's lab has shown that HIF is essential for blood cell and blood vessel development during embryogenesis. Because a solid tumor cannot grow unless it acquires new blood vessels from surrounding host tissues, HIF also appears to be necessary for tumor progression.
Mutations in at least three genes well known to suppress tumor growth can lead to HIF stimulation and the growth of blood vessels in tumors. By identifying the molecules that require HIF's ability to promote blood vessel growth and tumor cell survival, Simon and her colleagues hope to develop a procedure that will cut off the tumor's oxygen supply and diminish the cancer cell's ability to metastasize.
Vascular defects in E9.5 Arnt/ placentas. H&E-stained Arnt+/+ (A,B) and Arnt/ (C,D) sections showing the presence of a chorionic plate (short arrows in A and C) in both animals, but lack of fetal vessels (long arrows in B) in the labyrinthine layer of the Arnt/ placenta (D). Original magnification in A,C: 80×; magnification of inset in B,D: 400×. (GC) Giant cells; (MD) maternal deciduum; (LT) labyrinthine trophoblast.
Source: Adelman DM, Gertsenstein M, Nagy A, Simon MC, Maltepe E. Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses. Genes Dev. 2000 Dec 15;14(24):3191-203.
We are studying the role of signaling molecules and transcription factors in regulating the process by which, during human embryonic development, some hemangioblastic stem cells develop into endothelial precursors (which go on to make blood vessels) and others develop into hematopoietic stem cells (which make blood cells). A better understanding of this process will offer insight into the ways in which some tumors are able to trick the body into developing the additional blood vessels those tumors need to grow.
CancerNet - Angiogenesis Inhibitors in the Treatment of Cancer
CancerNet - Antiangiogenesis Information