Associate Professor with Tenure
Dr. Rappolee is the current Graduate Officer for the Reproductive Sciences Program. Our lab’s focus is on intracellular communication during high-risk time periods of human embryonic development as the embryo prepares to implant into the uterus, and embryonic and placental trophoblast stem cells expand their populations and then subpopulations undergo essential differentiation required soon after implantation for the survival of the conceptus. We primarily focus on the impact of stress and stress enzymes during early mammalian development. We have found that stress enzymes control the homeostatic response to stress in embryos and stem cells that can lead to cell survival and proliferation.
But, at higher stress levels stress enzymes regulate differentiation events in placental stem cells and embryos. In both embryonic and placental stem cells, stress causes loss of transcription factors mediating pluripotency and gain of transcription factors mediating differentiation. Stress enzymes like stress-activated protein kinase/jun kinase (SAPK/JNK) and AMP-activated protein kinase (AMPK) mediate both homeostatic and developmental effects and collaborate on mediating stress induced differentiation largely through unique synergistic mechanisms. A variety of experimental stressors such as hyperosmolar stress, and clinically relevant stressors such as oxygen levels and benzopyrene (cigarette tar) have similar effects in inducing stress enzymes to mediate low dose homeostasis and higher dose differentiation of stem cells and embryos. The work has significant and profound implications for the mechanisms leading to the normal high loss of embryos soon after implantation and should lead to improvements in human in vitro fertilization and assisted reproductive technologies and to isolation and maintenance of higher quality embryonic stem cells.
- Rappolee DA, Xie,Y, Zhou S, Puscheck, EE. Stress responses at the endometrial-placental interface regulate villous placental differentiation from trophoblast stem cells. Reproduction, 145(5):R139-55. (2013) PMID23463790
- Awonuga AO, Yang Y, Rappolee DA . When Stresses Collide. Invited Commentary. (2013) Biol.Repro. 89(3):74,1-2 PMID23946542
- Xie Y, Awonuga AO, Rings EHHM, Puscheck EE, Rappolee DA. Stress induces AMPK-dependent loss of potency factors Id2 and Cdx2 in early embryos and stem cells. Stem Cells and Development 22(10):1564-75(2013). PMID23316940 COVER
- Xie Y, Zhou S, Jiang Z, Puscheck EE, Lee I, Parker G, Huttemann M, and Rappolee, DA. Hypoxic stress induces SAPK-dependent, imbalanced trophoblast stem cell differentiation but does not sustain it due to mitochondrial insufficiency. (2014). In Press Stem Cell Research
- Slater J, Zhou S, Xie Y, Puscheck EE, Rappolee DA . Stress-Induced Enzyme Activation Primes Murine Embryonic Stem Cells to Differentiate toward Extraembryonic Lineages. Stem Cells and Development. In Press (2014).