Review
Cell Biology
Doris Chen, Wanjia Yu, Laura Aitken, Frank Gunn-Moore
Summary: FRMD6, also known as Willin, is an upstream regulator of Hippo signaling that modulates actin cytoskeleton dynamics and plays important roles in the nervous system, including neuronal differentiation, myelination, nerve injury repair, and vesicle exocytosis. Recent studies suggest a potential role for Willin/FRMD6 in Alzheimer's disease through its actions in cellular perturbations related to the pathogenesis of AD.
Article
Cell Biology
Doris Chen, Wanjia Yu, Laura Aitken, Frank Gunn-Moore
Summary: This study identifies Willin/FRMD6 as a potential risk gene for Alzheimer's disease (AD), and demonstrates the direct effects of A beta on its expression. The study also reveals mitochondrial oxidative stress as a novel mechanism underlying the role of Willin/FRMD6 in AD pathogenesis. Additionally, the study shows that knockdown of Willin/FRMD6 leads to mitochondrial dysfunction and upregulation of ERK1/2 signaling, which are key early features of AD. Increasing Willin/FRMD6 expression may serve as a therapeutic strategy for protecting against A beta-induced mitochondrial and neuronal dysfunction.
Article
Cell Biology
Truc Phan Hoang Le, Nga Thi Thanh Nguyen, Duong Duy Thai Le, Muhammad Ayaz Anwar, Sang Yoon Lee
Summary: In this study, PIP5Ka was found to act as an activator of the Hippo pathway by interacting and colocalizing with Merlin. This interaction promoted PIP2-dependent Merlin activation and induced the local recruitment and activation of LATS1 on the PIP2-rich plasma membrane, resulting in the negative regulation of YAP/TAZ activity.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Pei Li, Jinsheng Wang, Lingran Zhi, Fengmei Cai
Summary: Linc00887 inhibits the progression of cervical cancer by sponging miR-454-3p and activating the FRMD6-Hippo signaling pathway, as confirmed through in vitro and in vivo experiments.
CANCER CELL INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Li Wang, Kyungsuk Choi, Ting Su, Bing Li, Xiaofeng Wu, Ruihui Zhang, Jordan H. Driskill, Hongde Li, Huiyan Lei, Pengfei Guo, Elizabeth H. Chen, Yonggang Zheng, Duojia Pan
Summary: This study reveals that upstream regulators of the Hippo signaling pathway can form functionally antagonizing condensates, and their coalescence provides a mode of counteracting the activity of biomolecular condensates.
Article
Cell Biology
Qiyue Chen, Kai Fan, Xi Chen, Xiaobo Xie, Li Huang, Guangbao Song, Weizhong Qi
Summary: This study investigates the role of Ezrin in synovial vessels in rheumatoid arthritis (RA) and its regulatory mechanisms. Ezrin plays a crucial role in proliferation, migration, and angiogenesis of vascular endothelial cells in RA by regulating the Hippo-YAP pathway and the PI3K/Akt signaling pathway. Inhibition of Ezrin or its downstream YAP pathway in AIA mice experiments may affect synovial angiogenesis and exacerbate the progression of RA.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Oncology
Tianzhuo Wang, Huiying Guo, Lei Zhang, Miao Yu, Qianchen Li, Jing Zhang, Yan Tang, Hongquan Zhang, Jun Zhan
Summary: FRMD6, a member of the 4.1 ezrin-radixin-moesin domain-containing protein family, is overexpressed in lung cancer tissues and is associated with poor outcomes in patients with lung squamous cell carcinoma and lung adenocarcinoma. FRMD6 promotes cell migration, proliferation, and tumor formation in lung cancer by interacting with and enhancing the mTOR signaling pathway. Knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in mouse models.
FRONTIERS OF MEDICINE
(2023)
Article
Cell Biology
Xiaohan Hu, Li Li, Fang Li, Yuan Yang, Jingnan An, Xinghua Zhou, Rui Zhang, Lingli Shi, He Zhao, Jian Wang, Yizhou Hu, Yunyun Xu
Summary: This study found that the transition from in situ growth to invasive dissemination in various tumor types is mainly mediated by the dynamic interaction between EMT and cell cycle, and most signaling receptors associated with both EMT and cell cycle are potential tumor suppressors. The top co-associated receptor, Neogenin, was found to inhibit the in situ growth and metastasis of colorectal cancer (CRC) and glioma by forming a complex with Merlin and promoting the phosphorylation of YAP. Neogenin protein level was associated with good prognosis and correlated with Merlin status in CRC and glioma, suggesting Neogenin as a potential therapeutic agent for these cancers.
CELL DEATH DISCOVERY
(2023)
Review
Oncology
Renya Zeng, Jixin Dong
Summary: Although major advancements have been made in cancer treatment, drug resistance remains a significant challenge. The Hippo signaling pathway is emerging as a key player in understanding how tumor cells develop resistance to anti-cancer drugs. This review highlights the role of the Hippo pathway in drug resistance and potential therapeutic interventions.
Article
Multidisciplinary Sciences
Robert F. Hennigan, Craig S. Thomson, Kye Stachowski, Nicolas Nassar, Nancy Ratner
Summary: Neurofibromatosis Type 2 is a genetic disease characterized by nerve tumors. Merlin, encoded by the NF2 gene, has a role in tumor suppressor activity. It was found that Merlin dimerizes through a FERM-FERM interaction. Dimerization controls interactions with specific binding partners and occurs after a transition from closed to open conformation.
Article
Multidisciplinary Sciences
Christina Priest, Rohith T. Nagari, Lara Bideyan, Stephen D. Lee, Alexander Nguyen, Xu Xiao, Peter Tontonoz
Summary: The study illustrates the role of BRAP in modulating the hepatic Hippo pathway by regulating MST2, impacting liver cell morphology and turnover. Loss of BRAP leads to significant morphological changes in the liver, increased hepatocyte proliferation, cell death, and inflammation. The altered Hippo pathway signaling in Brap knockout mice affects liver lipid accumulation in dietary models of obesity, highlighting its relevance to human liver disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Maria Brooun, Willi Salvenmoser, Catherine Dana, Marius Sudol, Robert Steele, Bert Hobmayer, Helen McNeill
Summary: This study reveals the role of the Hippo pathway in regulating axis formation in cnidarian Hydra, suggesting its importance in early metazoan evolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Wei Wang, Chang'an Zhao, Fang Quan, Pengfei Zhang, Yuan Shao, Lifeng Liu
Summary: The downregulation of FRMD6 in thyroid cancer suppresses proliferation and invasion, promotes apoptosis and cell cycle arrest. Further studies show that FRMD6 inhibits tumor development by regulating the phosphorylation levels of oncogenic YAP1.
Article
Cell Biology
Ning Ding, Pibao Li, Huiqing Li, Yunlong Lei, Zengzhen Zhang
Summary: The RhoA/ROCK-ezrin/Syk-MyD88/IRAK1 axis plays an important role in the LPS-induced production of pro-inflammatory cytokines in pulmonary alveolar epithelial cells.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Biology
Lijuan Ma, Li Liu, Min Ji, Liping Su, Yaling Guan, Jinling Xiao, Hongwei Pu
Summary: The aim of this study was to analyze the role of Ezrin in esophageal squamous cell carcinoma (ESCC) and investigate potential therapeutic targets for ESCC by interfering with Ezrin expression. The results showed that Ezrin expression differed significantly among patients with different clinical stage ESCC and had a significant correlation with YAP(1)/CTGF levels. Knockdown of Ezrin expression inhibited ESCC cell biology and was involved in ESCC progression through the Hippo signaling pathway.
OPEN LIFE SCIENCES
(2023)
Article
Optics
Georgina E. Shillito, Lewis Mcmillan, Graham D. Bruce, Kishan Dholakia
Summary: The ability to identify the chemical contents of a sealed container without extracting a sample can be achieved using inverse spatially offset Raman spectroscopy (ISORS). This study explores a variant of ISORS called focus-matched ISORS and compares its relative advantages with traditional ISORS for different optical properties of the sample and container.
Article
Materials Science, Multidisciplinary
Kishan S. Menghrajani, Mingzhou Chen, Kishan Dholakia, William L. Barnes
Summary: Raman spectroscopy is a powerful technique for fingerprinting materials and molecules, but fluorescence interference is a common issue. Wavelength-modulated Raman spectroscopy can reduce fluorescence background, allowing clear recording of desired Raman signals. While studying vibrational strong coupling, advantages of the wavelength-modulated Raman approach are found, but results on strong coupling remain inconclusive, calling for further research.
ADVANCED OPTICAL MATERIALS
(2022)
Article
Genetics & Heredity
Suliman H. Yagoub, Jeremy G. Thompson, Antony Orth, Kishan Dholakia, Brant C. Gibson, Kylie R. Dunning
Summary: This study designed and fabricated a micrometer scale device to simplify the intracytoplasmic sperm injection procedure, aiming to improve embryo production and reduce variability among operators. The device demonstrated successful embryo culture and microinjection capabilities without the need for a holding pipette, enhancing traceability and efficiency in the process.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2022)
Article
Genetics & Heredity
Suliman H. Yagoub, Megan Lim, Tiffany C. Y. Tan, Darren J. X. Chow, Kishan Dholakia, Brant C. Gibson, Jeremy G. Thompson, Kylie R. Dunning
Summary: A novel photopolymerized device is presented for housing and preserving oocytes and embryos during vitrification, simplifying the procedure and improving traceability.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2022)
Article
Optics
Y. Arita, G. D. Bruce, E. M. Wright, S. H. Simpson, P. Zemanek, K. Dholakia
Summary: We have demonstrated a method of all-optical sympathetic cooling of a laser-trapped microsphere to sub-Kelvin temperatures, achieved through optical binding with a feedback-cooled adjacent particle. Our study opens up possibilities for multi-particle quantum entanglement and sensing in levitated optomechanics.
Article
Neurosciences
Marissa C. Vacher, Claire S. Durrant, Jamie Rose, Ailsa J. Hall, Tara L. Spires-Jones, Frank Gunn-Moore, Mark P. Dagleish
Summary: Toothed whales, such as odontocetes, develop neuropathology similar to Alzheimer's disease, including amyloid plaques and hyperphosphorylated tau accumulation, suggesting that they may be affected by AD-like neurodegeneration.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Article
Chemistry, Medicinal
Ondrej Benek, Michaela Vaskova, Marketa Miskerikova, Monika Schmidt, Rudolf Andrys, Aneta Rotterova, Adam Skarka, Jana Hatlapatkova, Jana Zdarova Karasova, Matej Medvecky, Lukas Hroch, Lucie Vinklarova, Zdenek Fisar, Jana Hroudova, Jiri Handl, Jan Capek, Tomas Rousar, Tereza Kobrlova, Rafael Dolezal, Ondrej Soukup, Laura Aitken, Frank Gunn-Moore, Kamil Musilek
Summary: In this study, new benzothiazolylurea-based inhibitors were developed for 17 beta-HSD10, a potential drug target for Alzheimer's disease and hormone-dependent cancer. The most potent compounds within this class were identified, showing submicromolar inhibitory activity and cell penetrability. These compounds also showed no off-target effects, cytotoxicity, or neurotoxicity. Compound 9, one of the most potent inhibitors, was found to be bioavailable and able to penetrate the blood-brain barrier.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Optics
Hyeonwoo Lee, Mingyu Lee, Hyeung Joo Lee, Juwon Yoon, Kishan Dholakia, Kyunghwan Oh
Summary: In this study, a novel all-fiber Bessel-like beam generator (BBG) was proposed and experimentally demonstrated to transport a dielectric particle over a distance exceeding 2mm. This was achieved by optimizing the multimode interference (MMI) in the BBG structure to create a Bessel-like beam with a propagation invariant length (PIL) and selecting an appropriate laser wavelength to suppress thermal effects. The impact of varying the diameter of the MMI region on the PIL and the transverse intensity profile of the Bessel-like beam was analyzed. This research paves the way for fiber optic applications such as novel beam shaping, optical transport, and optical imaging.
OPTICS AND LASERS IN ENGINEERING
(2023)
Article
Biochemical Research Methods
George O. Dwapanyin, Darren J. X. Chow, Tiffany C. Y. Tan, Nicolas S. Dubost, Josephine M. Morizet, Kylie R. Dunning, Kishan Dholakia
Summary: Embryo quality is a crucial factor for live birth outcomes, but a reliable diagnostic method for embryo quality is still lacking in the IVF clinic. In this study, we demonstrate that digital holographic microscopy (DHM) can rapidly and non-invasively assess the refractive index of mouse embryos, providing valuable information about their lipid content. DHM detected spatio-temporal changes in refractive index during embryo development, reflecting the accumulation of intracellular lipid, which is known to compromise embryo health. DHM may offer a promising non-invasive diagnostic method for accurately assessing embryo quality.
BIOMEDICAL OPTICS EXPRESS
(2023)
Article
Multidisciplinary Sciences
Gavrielle R. Untracht, Mingzhou Chen, Philip Wijesinghe, Josep Mas, Harold T. Yura, Dominik Marti, Peter E. Andersen, Kishan Dholakia
Summary: The penetration depth of optical coherence tomography (OCT) is greater than conventional microscopy, but signal reduction with depth is a challenge. This study explores the role of multiple scattering in OCT image contrast and introduces a geometry that separates the incident and collection fields, enhancing contrast at depth. Theoretical and experimental results demonstrate a significant improvement in contrast, with a ninefold enhancement observed in biological samples.
Article
Cell Biology
Mustafa Elshani, In Hwa Um, Steve Leung, Paul A. Reynolds, Alex Chapman, Mary Kudsy, David J. Harrison
Summary: This study investigates the expression of NFE2L1 in podocytes and its correlation with kidney disease. The results show that NFE2L1 expression is decreased in renal diseases, and its nuclear expression is reduced under PAN treatment.
Article
Physics, Multidisciplinary
Yoshihiko Arita, Stephen H. Simpson, Graham D. Bruce, Ewan M. Wright, Pavel Zemanek, Kishan Dholakia
Summary: By studying the rotation of birefringent microspheres trapped in vacuum and set into rotation by circularly polarised light, the authors explain the stable translational motion exhibited by these spheres. They demonstrate that fast rotation reduces the effect of azimuthal spin forces, resulting in nano-scale limit cycles at reduced pressures. This research has implications for designing high-stability rotors with enhanced centripetal loads and improving cooling methods for autonomous limit cycle oscillations, potentially leading to the study of non-equilibrium quantum effects.
COMMUNICATIONS PHYSICS
(2023)
Article
Optics
Jerin Geogy George, Kishan Dholakia, Shanti Bhattacharya
Summary: In this paper, a design and generation method for sidelobe-suppressed Bessel-like beams (SSBB) is described, which enhances the contrast for light-sheet imaging by suppressing the sidelobes. The interference of two Bessel beams with slightly different wavevectors is used to achieve this sidelobe suppression. The designed phase function can be realized using a spatial light modulator to generate the SSBB.
Article
Optics
Roopam K. Gupta, Nils Hempler, Graeme P. A. Malcolm, Kishan Dholakia, Simon J. Powis
Summary: T cells of the adaptive immune system are effectively protected against pathogenic challenges. Traditional labelling methods are time-consuming and expensive, but digital holographic microscopy with deep learning proves to be a faster and more cost-effective alternative. The combination of DHM and deep learning achieves high throughput and accuracy in classifying CD4+ and CD8+ T cell subsets.
Article
Optics
Xiao-Yong Duan, Graham D. Bruce, Feng Li, Kishan Dholakia
Summary: We analytically demonstrate the existence of an asymmetric optical binding force between two identical particles. This force arises from the asymmetric forward and backward scattering due to the coupling interactions between electric and magnetic dipoles. We show the rich dynamics of this phenomenon and discuss the conditions for the emergence of the asymmetric binding force.