Browsing by Author "Huang, Qiang"

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Open Access
Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF-PU.1-DPP4 Axis.
(Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021-10) Wang, Lihua; Wang, Ergang; Prado Balcazar, Jorge; Wu, Zhenzhen; Xiang, Kun; Wang, Yi; Huang, Qiang; Negrete, Marcos; Chen, Kai-Yuan; Li, Wei; Fu, Yujie; Dohlman, Anders; Mines, Robert; Zhang, Liwen; Kobayashi, Yoshihiko; Chen, Tianyi; Shi, Guizhi; Shen, John Paul; Kopetz, Scott; Tata, Purushothama Rao; Moreno, Victor; Gersbach, Charles; Crawford, Gregory; Hsu, David; Huang, Emina; Bu, Pengcheng; Shen, Xiling
Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9^KRAB or CRISPR/dCas9^HDAC revealed that individual PU.1-remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment-induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis.
Open Access
Intravital imaging of mouse embryos
(Science, 2020-04-10) Huang, Qiang; Cohen, Malkiel A; Alsina, Fernando C; Devlin, Garth; Garrett, Aliesha; McKey, Jennifer; Havlik, Patrick; Rakhilin, Nikolai; Wang, Ergang; Xiang, Kun; Mathews, Parker; Wang, Lihua; Bock, Cheryl; Ruthig, Victor; Wang, Yi; Negrete, Marcos; Wong, Chi Wut; Murthy, Preetish KL; Zhang, Shupei; Daniel, Andrea R; Kirsch, David G; Kang, Yubin; Capel, Blanche; Asokan, Aravind; Silver, Debra L; Jaenisch, Rudolf; Shen, Xiling
Embryonic development is a complex process that is unamenable to direct observation. In this study, we implanted a window to the mouse uterus to visualize the developing embryo from embryonic day 9.5 to birth. This removable intravital window allowed manipulation and high-resolution imaging. In live mouse embryos, we observed transient neurotransmission and early vascularization of neural crest cell (NCC)–derived perivascular cells in the brain, autophagy in the retina, viral gene delivery, and chemical diffusion through the placenta. We combined the imaging window with in utero electroporation to label and track cell division and movement within embryos and observed that clusters of mouse NCC-derived cells expanded in interspecies chimeras, whereas adjacent human donor NCC-derived cells shrank. This technique can be combined with various tissue manipulation and microscopy methods to study the processes of development at unprecedented spatiotemporal resolution.
Open Access
Longitudinal intravital imaging of mouse placenta.
(Science advances, 2024-03) Zhu, Xiaoyi; Huang, Qiang; Jiang, Laiming; Nguyen, Van-Tu; Vu, Tri; Devlin, Garth; Shaima, Jabbar; Wang, Xiaobei; Chen, Yong; Ma, Lijun; Xiang, Kun; Wang, Ergang; Rong, Qiangzhou; Zhou, Qifa; Kang, Yubin; Asokan, Aravind; Feng, Liping; Hsu, Shiao-Wen D; Shen, Xiling; Yao, Junjie
Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.
Open Access
Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy
(Light: Science & Applications, 2022-12) Zhu, Xiaoyi; Huang, Qiang; DiSpirito, Anthony; Vu, Tri; Rong, Qiangzhou; Peng, Xiaorui; Sheng, Huaxin; Shen, Xiling; Zhou, Qifa; Jiang, Laiming; Hoffmann, Ulrike; Yao, Junjie
AbstractHigh-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, and tracking fast pathophysiological activities at the microvessel level, which will enable advances in current queries in neurovascular and brain metabolism research, including stroke, dementia, and acute brain injury. Further, real-time imaging of oxygen saturation of hemoglobin (sO2) can capture fast-paced oxygen delivery dynamics, which is needed to solve pertinent questions in these fields and beyond. Here, we present a novel ultrafast functional photoacoustic microscopy (UFF-PAM) to image the whole-brain hemodynamics and oxygenation. UFF-PAM takes advantage of several key engineering innovations, including stimulated Raman scattering (SRS) based dual-wavelength laser excitation, water-immersible 12-facet-polygon scanner, high-sensitivity ultrasound transducer, and deep-learning-based image upsampling. A volumetric imaging rate of 2 Hz has been achieved over a field of view (FOV) of 11 × 7.5 × 1.5 mm3 with a high spatial resolution of ~10 μm. Using the UFF-PAM system, we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia, sodium nitroprusside, and stroke. We observed the mouse brain’s fast morphological and functional changes over the entire cortex, including vasoconstriction, vasodilation, and deoxygenation. More interestingly, for the first time, with the whole-brain FOV and micro-vessel resolution, we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization (SD) wave. We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions.