Browsing by Author "Cheng, Hui"

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    System modeling reveals the molecular mechanisms of HSC cell cycle alteration mediated by Maff and Egr3 under leukemia
    (BMC, 2017-10-03) Li, Rudong; Wang, Yin; Cheng, Hui; Liu, Gang; Cheng, Tao; Liu, Yunlong; Liu, Lei; Medical and Molecular Genetics, School of Medicine
    Background Molecular mechanisms of the functional alteration of hematopoietic stem cells (HSCs) in leukemic environment attract intensive research interests. As known in previous researches, Maff and Egr3 are two important genes having opposite functions on cell cycle; however, they are both highly expressed in HSCs under leukemia. Hence, exploring the molecular mechanisms of how the genes act on cell cycle will help revealing the functional alteration of HSCs. Results We herein utilize the bioinformatic resources to computationally model the acting mechanisms of Maff and Egr3 on cell cycle. Using the data of functional experiments as reference, molecular acting mechanisms are optimally enumerated through model selection. The results are consolidated by evidences from gene sequence analysis, thus having enhanced the confidence of our pilot findings, which suggest that HSCs possibly undergo a “adaptation - suppression” process in response to the malignant environment of leukemia. Conclusion As a pilot research, our results may provide valuable insights for further experimental studies. Meanwhile, our research method combining computational modeling and data from functional experiments can be worthwhile for knowledge discovery; and it can be generalized and extended to other biological/biomedical studies. Electronic supplementary material The online version of this article (doi:10.1186/s12918-017-0467-4) contains supplementary material, which is available to authorized users.
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    Taperin bundles F-actin at stereocilia pivot points enabling optimal lifelong mechanosensitivity
    (Rockefeller University Press, 2025) Belyantseva, Inna A.; Liu, Chang; Dragich, Abigail K.; Miyoshi, Takushi; Inagaki, Sayaka; Imtiaz, Ayesha; Tona, Risa; Zuluaga-Osorio, Karen Sofia; Hadi, Shadan; Wilson, Elizabeth; Morozko, Eva; Olszewski, Rafal; Yousaf, Rizwan; Sokolova, Yuliya; Riordan, Gavin P.; Aston, S. Andrew; Rehman, Atteeq U.; Fenollar Ferrer, Cristina; Wisniewski, Jan; Gu, Shoujun; Nayak, Gowri; Goodyear, Richard J.; Li, Jinan; Krey, Jocelyn F.; Wafa, Talah; Faridi, Rabia; Adadey, Samuel Mawuli; Drummond, Meghan; Perrin, Benjamin; Winkler, Dennis C.; Starost, Matthew F.; Cheng, Hui; Fitzgerald, Tracy; Richardson, Guy P.; Dong, Lijin; Barr-Gillespie, Peter G.; Hoa, Michael; Frolenkov, Gregory I.; Friedman, Thomas B.; Zhao, Bo; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Stereocilia are rod-like mechanosensory projections consisting of unidirectionally oriented actin filaments that extend into the inner ear hair cell cytoskeleton, forming dense rootlets. Taperin (TPRN) localizes to the narrowed-down base of stereocilia, where they pivot in response to sound and gravity. We show that TPRN-deficient mice have progressive deafness characterized by gradual asynchronous retraction and fusion of outer and inner hair cell stereocilia, followed by synaptic abnormalities. Stereocilia that lack TPRN develop warped rootlets with gradual loss of TRIOBP-5 and ANKRD24 from mechanosensory rows starting postnatally. In contrast, TPRN overexpression causes excessive F-actin bundling, extra rows, and over-elongation of stereocilia during development. Purified full-length mouse TPRN cross-links F-actin into bendable bundles reflecting in vivo data. This F-actin-bundling ability is attributed to the TPRN N-terminal region. TPRN interacts with the membrane receptor PTPRQ, connecting the F-actin core to the plasma membrane, stabilizing stereocilia. Thus, TPRN is a specialized F-actin bundler strategically located to augment stereocilia rootlet formation and their pivot point flexibility for sustained sound-induced deflections.