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19. Binding Topologies of Amino Acid Binary Systems by Infrared Multiphoton Dissociation (IRMPD) Spectroscopy

Author

Wang, Haolu

Abstract

Studies of amino acids are essential because they are one of the building blocks of larger biomolecules, and it is crucial for us to understand how they interact with each other to fulfill all these various biological functions in our daily life. One interesting and noticeable fact from previous studies is that the amino acids found in proteins almost always possess only the left-handed configuration. When an enantiomer of a chiral molecule shows a stronger interaction with one enantiomer of another chiral molecule than with its mirror image, chirality recognition is observed. In the past few decades, gas phase rotational and vibrational spectroscopies have been used to investigate non-covalent interactions in chiral molecular aggregates and in particular homochiral and heterochiral molecular pairs. Among them, infrared multiphoton dissociation (IRMPD) spectroscopy is a powerful spectroscopic technique for its high detection sensitivity and its capability to access larger chiral molecular systems without the complications in solution, while providing structural information. The following chapters include detailed work using IRMPD spectroscopy to determine the conformational and energetic relationship of the proton bound homochiral and heterochiral serine-asparagine and valine-asparagine dimers, as well as whether chirality recognition could be observed between the binary systems of interest. How the non-covalent inter/intra-molecular interactions affect the preferred binary structures, in particular the role of a polar or a non-polar sidechain, is also investigated.

Published
2022
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24. Designer artificial membrane binding proteins to direct stem cells to the myocardium† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c9sc02650a

Author

Xiao, Wenjin, Green, Thomas I. P., Liang, Xiaowen, Delint, Rosalia Cuahtecontzi, Perry, Guillaume, Roberts, Michael S., Le Vay, Kristian, Back, Catherine R., Ascione, Raimomdo, Wang, Haolu, Race, Paul R., and Perriman, Adam W.

Subjects
Chemistry
Abstract

We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells., We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells. This is achieved via the rational design of a chimeric protein–polymer surfactant cell membrane binding construct, comprising the cardiac fibronectin (Fn) binding domain of the bacterial adhesin protein CshA fused to a supercharged protein. Significantly, the protein–polymer surfactant hybrid spontaneously inserts into the plasma membrane of stem cells without cytotoxicity, instilling the cells with a high affinity for immobilized fibronectin. Moreover, we show that this cell membrane reengineering approach significantly improves retention and homing of stem cells delivered either intracardially or intravenously to the myocardium in a mouse model.

Published
2019

26. A Monochromophoric Approach to Succinct Ratiometric Fluorescent Probes without Probe-Product Crosstalk

Author

Xin, Kai, primary, Li, Xinxing, additional, Guo, Yinghua, additional, Zhong, Youhuan, additional, Wang, Jungang, additional, Yang, Haotian, additional, Zhao, Jie, additional, Guo, Chunlei, additional, Huang, Yunxia, additional, Lei, Zuhai, additional, Ying, Yi-Lun, additional, Luo, Xiao, additional, Wang, Haolu, additional, Qian, Xuhong, additional, Yang, Wen, additional, Liang, Xiaowen, additional, and Yang, Youjun, additional

Published
2021
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30. Imaging-based vascular-related biomarkers for early detection of acetaminophen-induced liver injury

Author

Wang, Haolu, Burke, Leslie J, Patel, Jatin, Tse, Brian W.C., Bridle, Kim R., Cogger, Victoria C., Li, Xinxing, Liu, Xin, Yang, Haotian, Crawford, Darrell H.G., Roberts, Michael S., Gao, Wenchao, Liang, Xiaowen, Wang, Haolu, Burke, Leslie J, Patel, Jatin, Tse, Brian W.C., Bridle, Kim R., Cogger, Victoria C., Li, Xinxing, Liu, Xin, Yang, Haotian, Crawford, Darrell H.G., Roberts, Michael S., Gao, Wenchao, and Liang, Xiaowen

Abstract

Acetaminophen (APAP) is the foremost cause of drug-induced liver injury in the Western world. Most studies of APAP hepatotoxicity have focused on the hepatocellular injury, but current hepatocyte-related biomarkers have delayed presentation time and a lack of sensitivity. APAP overdose can induce hepatic microvascular congestion, which importantly precedes the injury of hepatocytes. However, the underlying molecular mechanisms remain unclear. It is imperative to discover and validate sensitive and specific translational biomarkers of APAP-induced liver injury. Methods: In this study, we assessed APAP toxicity in sinusoidal endothelial cells and hepatocytes in mice treated with overdose APAP at different time points. The underlying mechanisms of APAP overdose induced sinusoidal endothelial cell injury were investigated by RT2 Profiler PCR arrays. The impact of APAP overdose on endothelial cell function was assessed by pseudovessel formation of endothelial cells in 2D Matrigel and in vivo hepatic vascular integrity using multiphoton microscopy. Finally, the effects of APAP overdose on oxygen levels in the liver and hepatic microcirculation were evaluated by contrast enhanced ultrasonography. Potential imaging-based vascular-related markers for early detection of APAP induced liver injury were assessed. Results: Our study confirmed that hepatic endothelial cells are an early and direct target for APAP hepatotoxicity. ICAM1-related cellular adhesion pathways played a prominent role in APAP-induced endothelial cell injury, which was further validated in primary human sinusoidal endothelial cells and human livers after APAP overdose. APAP overdose impacted pseudovessel formation of endothelial cells and in vivo hepatic vascular integrity. Use of ultrasound to detect APAP-induced liver injury demonstrated that mean transit time, an imaging-based vascular-related biomarker, was more sensitive and precise for early detection of APAP hepatotoxicity and monitoring the treat

Published
2020

34. C24‐Ceramide Drives Gallbladder Cancer Progression Through Directly Targeting Phosphatidylinositol 5‐Phosphate 4‐Kinase Type‐2 Gamma to Facilitate Mammalian Target of Rapamycin Signaling Activation

Author

Zhang, Yonglong, primary, Wang, Hui, additional, Chen, Tao, additional, Wang, Haolu, additional, Liang, Xiaowen, additional, Zhang, Yuchen, additional, Duan, Jinlin, additional, Qian, Shenjiao, additional, Qiao, Ke, additional, Zhang, Lei, additional, Liu, Yanfeng, additional, and Wang, Jian, additional

Published
2020
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37. Sequential PDT and PTT Using Dual‐Modal Single‐Walled Carbon Nanohorns Synergistically Promote Systemic Immune Responses against Tumor Metastasis and Relapse

Author

Yang, Jingxing, primary, Hou, Mengfei, additional, Sun, Wenshe, additional, Wu, Qinghe, additional, Xu, Jia, additional, Xiong, Liqin, additional, Chai, Yimin, additional, Liu, Yuxin, additional, Yu, Meihua, additional, Wang, Haolu, additional, Xu, Zhi Ping, additional, Liang, Xiaowen, additional, and Zhang, Chunfu, additional

Published
2020
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43. Imaging-based vascular-related biomarkers for early detection of acetaminophen-induced liver injury

Author

Wang, Haolu, primary, Burke, Leslie J., additional, Patel, Jatin, additional, Tse, Brian WC., additional, Bridle, Kim R., additional, Cogger, Victoria C., additional, Li, Xinxing, additional, Liu, Xin, additional, Yang, Haotian, additional, Crawford, Darrell H. G., additional, Roberts, Michael S., additional, Gao, Wenchao, additional, and Liang, Xiaowen, additional

Published
2020
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44. Impact of age on risk of lymph node positivity in patients with colon cancer

Author

Wang, Haolu, Lu, Hao, Yang, Haotian, Zhang, Xianwen, Thompson, Rik, Roberts, Michael, Hu, Zhiqian, Liang, Xiaowen, Li, Xinxing, Wang, Haolu, Lu, Hao, Yang, Haotian, Zhang, Xianwen, Thompson, Rik, Roberts, Michael, Hu, Zhiqian, Liang, Xiaowen, and Li, Xinxing

Abstract

Background: Lymph node (LN) positivity is a prognostic indicator in patients with colon cancer regardless of age, and age is an important parameter that impacts therapeutic recommendations. But little is known about the impact of age on LN positivity in patients with colon cancer. Methods: We analyzed 257,334 patients with colon cancer diagnosed from SEER database. Logistic regression was used to examine the association of age and LN positivity. Poisson regression was used to evaluate whether age was associated with the number of positive LNs. Results: LN positivity was inversely associated with age (P < .001 for each T stage). Age was predictive of LN positivity after adjustment for number of LNs examined and other covariates (P < .001 for each T stage). Adjusted odds ratios (ORs) for LN positivity for age 20 to 39 vs 80+ were 3.06 for stage T1 (95 % CI, 2.09 to 4.48), 2.46 for stage T2 (95 % CI, 2.00 to 3.02), 1.77 for stage T3 (95 % CI, 1.62 to 1.93), and 1.68 for stage T4 (1.51 to 1.86). Young age was a significant predictor of an increased number of positive LNs (P < .005 for each T stage). Conclusion: Young age at diagnosis is associated with an increased risk of LN positivity. LN examination and resection could aid younger patients more with detection and removal of metastasis. Guidelines that define postdetection interventions may be needed to limit the overtreatment of older patients, who may be vulnerable to unnecessary tests and treatments.

Published
2019

45. Identification and characterization of TM4SF1+tumor self-seeded cells

Author

Yang, Haotian, Wang, Haolu, He, Yaowu, Yang, Yang, Thompson, Erik W., Xia, Di, Burke, Leslie J., Cao, Lu, Hooper, John D., Roberts, Michael S., Crawford, Darrell H.G., and Liang, Xiaowen

Abstract

Tumor self-seeding is a process whereby circulating tumor cells (CTCs) recolonize the primary tumor, which promotes tumor growth, angiogenesis, and invasion. However, the detailed nature and functions of tumor self-seeded cells (TSCs) have not been well defined due to challenges in tracking and isolating TSCs. Here, we report an accurate animal model using photoconvertible tagging to recapitulate the spontaneous process of tumor self-seeding and identify TSCs as a subpopulation of primary tumor cells with enhanced invasiveness and survival. We demonstrate transmembrane-4-L-six-family-1(TM4SF1) as a marker of TSCs, which promotes migration, invasion, and anchorage-independent survival in cancer cells. By analyzing single-cell RNA sequencing datasets, we identify a potential TSC population with a metastatic profile in patients with cancer, which is detectable in early-stage disease and expands during cancer progression. In summary, we establish a framework to study TSCs and identify emerging cell targets with diagnostic, prognostic, or therapeutic potential in cancers.

Published
2024
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46. Using bacterial adhesins to direct human stem cells to the myocardium

Author

Xiao, Wenjin, Green, Thomas, Liang, Xiaowen, PERRY, Guillaume, Cuahtecontzi Delint, Rosalia, Wang, Haolu, Barker, Robert, le Vay, Kris, Roberts, Michael, Race, Paul, Perriman, Adam, School of Cellular and Molecular Medicine, University of Bristol [Bristol], University of Queensland - The Diamantina Institute, University of Queensland [Brisbane], Laboratoire d'Electronique et Electromagnétisme (L2E), Sorbonne Université (SU), School of Physical Sciences [Canterbury], University of Kent [Canterbury], and Univ Kent, Sch Phys Sci, Canterbury, Kent, England

Subjects
Adhesion proteins, [SPI.ELEC]Engineering Sciences [physics]/Electromagnetism, Cell homing, Cell-based therapy, Fusion Proteins, Synthetic Biology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

47. 17 Multiscale correlative imaging of the brain

Author

Baldeweck, Thérèse, Balu, Mihaela, Batista, Ana, Vecker, Wolfgang, Belousov, Vsevolod V, Breinig, Hans Georg, Breymayer, Jasmin, Brizion, Sébastien, Castello, Marco, Chandra, Dhyan, Choi, Heejin, Decencière, Etienne, Diaspro, Alberto, Donitzky, Christoph, Dudenkova, Varvara V., Druzhkova, Irina N., Harris, Ronald M., Hoffman, Robert M., Holmes, Amy, Huck, Volker, Joshi, Suchitra, Kaiser, Wolfgang, Kalinina, Sviatlana, Kantelhardt, Sven R., Kapur, Jaideep, Kelly, Kristen M., König, Karten, Koudoro, Serge, Krueger, Arnd, Lanzano, Luca, Liang, Xiaowen, Liu, Xin, Lukina, Maria M., Mascaro, Anna Letizia Allegra, Melia, Meghan J.O., Mess, Christian, Mishina, Natalie M., Pavone, Francesco S., Periasamy, Ammasi, Rehman Alam, Shagufta, Roberts, Michael S., Pena, Ana-Maria, Rowlands, Christoph, Rück, Angelika, Sacconi, Leonardo, Scipioni, Lorenzo, Sergeeva, Tatiana F., Shcheslavskiy, Vladislav I., Shirmanova, Marina V., Silvestri, Ludovico, So, Peter T.C., Studier, Hauke, Svindrych, Zdenek, Tancrede-Bohin, Emmanuelle, Thorling, Camilla, Tromberg, Bruce j., Uchugonova, Aisada, Vicidomini, Giuseppe, Victorin, Steeve, Wallrabe, Horst, Wang, Haolu, Weinigel, Martin, Yew, Elijah, Zachary, Christopher B., and Zagaynova, Elena V.

Subjects
Correlative imaging, Geology, Biomedical engineering
Published
2018
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