Janes, T. Sciuto, P. Kang, SC. Jaminet, A. Dvorak, M. Grant, E.
Ravasz Regan , W. Katie Bentley, Kyle I. Regulatory Networks.
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Teaching Experience. Teaching Statement. Curriculum Vitae. Endothelial cells are great examples of complex functional coordination.
This cell type displays extraordinary functional heterogeneity across the vasculature, a result of context-dependent, combinatorial use of a sizable functional arsenal. Deciphering how this coordination occurs remains problematic, in spite of detailed knowledge about individual functions. The central questions driving my research revolve around this problem: Are there general principles that govern coordination between regulatory modules?
Can we use such principles to build a theoretical foundation for modeling multi-module regulatory systems? Is there a critical type of modularity that is key to deciphering a cell's higher-level responses? We have recently defined dynamical modules as robust, multistable regulatory switches. Using this definition, we propose three general principles that characterize coordination between these regulatory modules.
We are in the process of developing appropriate quantitative measures in order to test their validity in Boolean regulatory networks. We have built a dynamically modular model of the mammalian cell cycle, and showed that this biological model obeys the three principles, while its randomized counterparts do not. We are now extending the cell cycle model with an apoptotic and DNA damage switch, them build the module responsible for growth factor signaling and cellular growth, an input module of the cell cycle engine in our current model. Biological noise-driven dynamic mosaic heterogeneity and functional bet hedging in vivo.
We have found a novel adaptive strategy used by endothelial cells to increase their phenotypic plasticity and protect tissues from sudden environmental change. Briefly, the endothelium of healthy organs can exploit biological noise to generate a spatially heterogeneous, slowly flickering mosaic of Willebrand factor vWF -positive and -negative cells. These dynamic mosaics only appear in specific organs and vascular beds, such as heart capillaries.tiodemitala.gq
A Dialogue of the Deaf: Fundamental Incompatibilities in the Regan-Liu Face-Off
Their absence damages heart capillary endothelial cells and neighboring cardiomyocytes, but does not affect other vessels. Our data point to a novel, tissue-specific strategy for homeostasis. Bistability in endothelial morphogenesis. In a recent Developmental Cell review I coauthored with Dr.
Katie Bentley , we explored the parallels between endothelial morphogenesis and the core principles of adaptive systems robotics. In a subsequent paper we showed that sensorimotor feedback can generate bistability in single endothelial cells sensing VEGF gradients at the angiogenic front. The FoxO1 transcription factor is expressed by most mammalian cells and it affects multiple cellular functions such as cell cycle, apoptosis, oxidative stress response, DNA repair, metabolism, aging and differentiation. Consequently, FoxO1 has been implicated in diseases as diverse as cancer, diabetes, muscle atrophy or Parkinson's disease, but its effects are cell-type specific and often paradoxical.
We have recently shown that endothelial FoxO1 is both necessary and sufficient for embryonic development. Loss of endothelial FoxO1 thus causes G1 arrest. Excess FoxO1 nonetheless fails to increase proliferation, as it also induces G2 arrest. Pharmacological elevation of FoxO1 may thus promote quiescence and ROS resistance in some tissues, but carries the risk of damaging the vasculature. Metabolite profiling in Akt- and Myc-overexpressing prostate cancer.
Disease Burden and Risk Factors : NCD Synergies
First, Liu dismisses the role of emotions in trade politics: cultural underpinnings and misperceptions matter as much as, if not more than, cold economics. You can cite quantitative evidence against a trade war left and right but are unlikely to win a single vote from American conservatives who take her fact-checking as a blatant attack on Trish Regan and the free world. Second, Liu is at best unwilling to look at the influences of electoral politics in the U. While insisting that China is a market economy with Chinese characteristics and private Chinese companies herald its global initiatives, she forgot that such a textbook narrative is insufficient to persuade an average Fox Business viewer and was counterproductive.
Most fundamentally, she dangerously ignored a powerful hypothesis of development that economic openness is underpinned by inclusive political processes. Disappointedly but expectedly, the Regan-Liu dialogue serves little in advancing broad U. It was a dialogue of the deaf, grounded in an overarching structure of a political trilemma.
Coined by political economist Dani Rodrik, the trilemma implies the inescapable incompatibilities of an integrated world economy, powerful nation-states, and democratic politics.
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No country can accomplish the three goals simultaneously. Today, the two world hegemons are inevitably trapped in the quagmire, with the U. If you're interested in writing for International Policy Digest - please send us an email via submissions intpolicydigest. Wenyuan Wu Read Next Latest Article.