Using a synthetic circuit as a probe, my lab will characterize how direct conversion and hyperproliferation affect the dynamics of transitions within a bistable circuit. a bistable switch), which can be more easily measured, modified, and modeled. State transitions from one cell fate to another represent transitions in large transcriptional networks that may be approximated by transitions in small transcriptional networks (e.g. transcriptional activity, proliferation) to cell state switching. MEASURING TRANSITION SPEED Characterizing the dynamics of proliferation-mediated transitions between cell statesīy examining the process of cellular decision-making in the synthetic context of reprogramming, we examine the contribution of developmentally-entangled systems-level phenomena (e.g. To effectively balance these tradeoffs, our lab constructs control systems to tailor expression of reprogramming factors to cellular capacity. Tradeoffs between transcription and replication limit cellular reprogramming, with excessive transcription limiting necessary cellular division. reprogramming, cancer).ĭESIGNING SOFTWARE TO MATCH HARDWARE Scaling circuit output to match cellular capacity These observations raise additional questions about the precise mechanisms by which hyperproliferation and hypertranscription enhance transitions in cellular state, which may refine our understanding of both synthetic and pathological cellular transformations (e.g. Hyperproliferation and hypertranscription drive rapid, robust conversion yet are often mutually inhibitory. software, 4647 The Ethnograph software, 50 EZ-Text package, 45 free/low-cost software, 4446 HyperRESEARCH software, 47,51 HyperTRANSCRIBE software. MOLECULAR PATHS TO RAPID REPROGRAMMING Hypertranscribing, hyperproliferating cells drive reprogramming Additionally, translating improved vectors to promote in vivo reprogramming will be an important long-term goal of my lab. Comparison of mouse and human reprogramming suggests mechanisms that limit the human system. With improved in vivo delivery vehicles via adeno-associated virus (AAVs), limitations in conversion efficiency in human cells remain the primary barrier to in vivo reprogramming therapies. Tissue regeneration to replace damaged or diseased cells endures as a prime objective in regenerative medicine. Philadelphia (PA): AACR Cancer Res 2022 82(12_Suppl):Abstract nr LB177.TOWARDS TISSUE REGENERATION Developing tools and insight to enable in vivo reprogramming. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022 2022 Apr 8-13. Widespread hypertranscription in aggressive human cancer. Hellmann, Uri Tabori, Annie Huang, Adam Shlien. Selvanathan, Jeffrey Toretsky, Matthew D. Our results provide fundamental insights into gene dysregulation across human cancers and may prove useful in identifying patients that would benefit from novel therapies.Ĭitation Format: Matthew Zatzman, Fabio Fuligni, Ryan Ripsman, Tannu Suwal, Lisa-Monique Edward, Rob Denroche, Gun Ho Jang, Faiyaz Notta, Steven Gallinger, Saravana P. Finally, patients with hypertranscribed mutations have improved response to immune checkpoint therapy. Single-cell analysis reveals hypertranscriptional clones, which dominate transcript production regardless of their size. There are various kinds of software that you can install on your Mac, and it is quite easy to manage those apps on macOS. Our data suggest that loss of transcriptional suppression underpins the hypertranscriptional phenotype. Business Software > HyperTRANSCRIBE How To Uninstall HyperTRANSCRIBE from Mac OS. It defines patient subgroups with worse survival, even within well-established subtypes. Hypertranscription is ubiquitous across cancer, especially in aggressive disease. Here, we developed a computational method to directly measure hypertranscription in 7,494 human tumors, spanning 31 cancer types. This is due in part to limitations of expression profiling methods, which assume equal RNA output between samples. Hypertranscription’s prevalence, underlying drivers and prognostic significance are undefined in primary human cancer. Hypertranscription is the genome-wide increase in RNA output. Cancers are often defined by the dysregulation of specific transcriptional programs however, the importance of global transcriptional changes is less understood.
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