IU Indianapolis ScholarWorks :: Browsing by Author "Chen, Xin"

Browsing by Author "Chen, Xin"

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A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2
(Springer Nature, 2023) Yin, Qian; Luo, Wei; Mallajosyula, Vamsee; Bo, Yang; Guo, Jing; Xie, Jinghang; Sun, Meng; Verma, Rohit; Li, Chunfeng; Constantz, Christian M.; Wagar, Lisa E.; Li, Jing; Sola, Elsa; Gupta, Neha; Wang, Chunlin; Kask, Oliver; Chen, Xin; Yuan, Xue; Wu, Nicholas C.; Rao, Jianghong; Chien, Yueh-hsiu; Cheng, Jianjun; Pulendran, Bali; Davis, Mark M.; Microbiology and Immunology, School of Medicine
The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.
Author Correction: α-Galactosylceramide and its analog OCH differentially affect the pathogenesis of ISO-induced cardiac injury in mice
(Springer Nature, 2022) Chen, Xin; Liu, Jie; Liu, Jie; Wang, Wen-Jia; Lai, Wen-Jing; Li, Shu-Hui; Deng, Ya-Fei; Zhou, Jian-Zhi; Yang, Sheng-Qian; Liu, Ying; Shou, Wei-Nian; Cao, Da-Yan; Li, Xiao-Hui; Pediatrics, School of Medicine
This corrects the article "α-Galactosylceramide and its analog OCH differentially affect the pathogenesis of ISO-induced cardiac injury in mice" in volume 41 on page 1416.
Direct Temporal Mode Measurement for the Characterization of Temporally Multiplexed High Dimensional Quantum Entanglement in Continuous Variables
(APS, 2020-05-29) Huo, Nan; Liu, Yuhong; Li, Jiamin; Cui, Liang; Chen, Xin; Palivela, Rithwik; Xie, Tianqi; Li, Xiaoying; Ou, Z. Y.; Physics, School of Science
Field-orthogonal temporal mode analysis of optical fields has recently been developed for a new framework of quantum information science. However, so far, the exact profiles of the temporal modes are not known, which makes it difficult to achieve mode selection and demultiplexing. Here, we report a novel method that measures directly the exact form of the temporal modes. This, in turn, enables us to make mode-orthogonal homodyne detection with mode-matched local oscillators. We apply the method to a pulse-pumped, specially engineered fiber parametric amplifier and demonstrate temporally multiplexed multidimensional quantum entanglement of continuous variables in telecom wavelength. The temporal mode characterization technique can be generalized to other pulse-excited systems to find their eigenmodes for multiplexing in the temporal domain.
Direct temporal mode measurement of photon pairs by stimulated emission
(American Physical Society, 2020-03) Chen, Xin; Li, Xiaoying; Ou, Z. Y.; Physics, School of Science
It is known that photon pairs generated from pulse-pumped spontaneous parametric processes can be described by independent temporal modes and form a multitemporal mode entangled state. However, the exact form of the temporal modes is not known even though the joint spectral intensity of photon pairs can be measured by the method of stimulated emission tomography. In this paper, we describe a feedback-iteration method which, combined with the stimulated emission method, can give rise to the exact forms of the independent temporal modes for the temporally entangled photon pairs.
FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036
(Springer Nature, 2021-05-12) Angus, Steven P.; Stuhlmiller, Timothy J.; Mehta, Gaurav; Bevill, Samantha M.; Goulet, Daniel R.; Olivares-Quintero, J. Felix; East, Michael P.; Tanioka, Maki; Zawistowski, Jon S.; Singh, Darshan; Sciaky, Noah; Chen, Xin; He, Xiaping; Rashid, Naim U.; Chollet-Hinton, Lynn; Fan, Cheng; Soloway, Matthew G.; Spears, Patricia A.; Jefferys, Stuart; Parker, Joel S.; Gallagher, Kristalyn K.; Forero-Torres, Andres; Krop, Ian E.; Thompson, Alastair M.; Murthy, Rashmi; Gatza, Michael L.; Perou, Charles M.; Earp, H. Shelton; Carey, Lisa A.; Johnson, Gary L.; Pediatrics, School of Medicine
Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.
Mode Structure of a Broadband High Gain Parametric Amplifier
(American Physical Society, 2021) Chen, Xin; Zhang, Jacob; Ou, Z. Y.; Physics, School of Science
A high gain parametric amplifier with a single-pass pulsed pump is known to generate broadband twin photon fields that are entangled in amplitude and phase but have complicated spectral correlation. Fortunately, they can be decomposed into independent temporal modes. However, the early treatment of the parametric interaction Hamiltonian at strong pumping does not consider the issue of the time-ordering problem of the interaction Hamiltonian and thus leads to the inaccurate conclusion that the mode structure and the temporal mode functions do not change as the gain increases. Recent studies have revealed the change of the spectrum with the gain of the process. In this paper we use an approach that is usually employed for treating nonlinear interferometers and avoids the time-ordering issue. This allows us to derive an evolution equation in differential-integral form. Numerical solutions for the high gain situation indicate a gain-dependent mode structure that has its mode distributions changed and mode functions broadened as the gain increases. This study will enable us to have a complete picture of the mode structure of parametric processes and produce high quality quantum sources for a variety of applications of quantum technology.
Monoallelically expressed noncoding RNAs form nucleolar territories on NOR-containing chromosomes and regulate rRNA expression
(eLife Sciences, 2024-01-19) Hao, Qinyu; Liu, Minxue; Daulatabad, Swapna Vidhur; Gaffari, Saba; Song, You Jin; Srivastava, Rajneesh; Bhaskar, Shivang; Moitra, Anurupa; Mangan, Hazel; Tseng, Elizabeth; Gilmore, Rachel B.; Frier, Susan M.; Chen, Xin; Wang, Chengliang; Huang, Sui; Chamberlain, Stormy; Jin, Hong; Korlach, Jonas; McStay, Brian; Sinha, Saurabh; Janga, Sarath Chandra; Prasanth, Supriya G.; Prasanth, Kannanganattu V.; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and Engineering
Out of the several hundred copies of rRNA genes arranged in the nucleolar organizing regions (NOR) of the five human acrocentric chromosomes, ~50% remain transcriptionally inactive. NOR-associated sequences and epigenetic modifications contribute to the differential expression of rRNAs. However, the mechanism(s) controlling the dosage of active versus inactive rRNA genes within each NOR in mammals is yet to be determined. We have discovered a family of ncRNAs, SNULs (Single NUcleolus Localized RNA), which form constrained sub-nucleolar territories on individual NORs and influence rRNA expression. Individual members of the SNULs monoallelically associate with specific NOR-containing chromosomes. SNULs share sequence similarity to pre-rRNA and localize in the sub-nucleolar compartment with pre-rRNA. Finally, SNULs control rRNA expression by influencing pre-rRNA sorting to the DFC compartment and pre-rRNA processing. Our study discovered a novel class of ncRNAs influencing rRNA expression by forming constrained nucleolar territories on individual NORs.
Muscle-specific regulation of right ventricular transcriptional responses to chronic hypoxia-induced hypertrophy by the muscle ring finger-1 (MuRF1) ubiquitin ligase in mice
(Biomed Central, 2018-09-21) Oakley, Robert H.; Campen, Matthew J.; Paffett, Michael L.; Chen, Xin; Wang, Zhongjing; Parry, Traci L.; Hillhouse, Carolyn; Cidlowski, John A.; Willis, Monte S.; Pathology and Laboratory Medicine, School of Medicine
BACKGROUND: We recently identified a role for the muscle-specific ubiquitin ligase MuRF1 in right-sided heart failure secondary to pulmonary hypertension induced by chronic hypoxia (CH). MuRF1-/- mice exposed to CH are resistant to right ventricular (RV) dysfunction whereas MuRF1 Tg + mice exhibit impaired function indicative of heart failure. The present study was undertaken to understand the underlying transcriptional alterations in the RV of MuRF1-/- and MuRF1 Tg + mice. METHODS: Microarray analysis was performed on RNA isolated from the RV of MuRF1-/-, MuRF1 Tg+, and wild-type control mice exposed to CH. RESULTS: MuRF1-/- RV differentially expressed 590 genes in response to CH. Analysis of the top 66 genes (> 2-fold or < - 2-fold) revealed significant associations with oxidoreductase, transcription regulation, and transmembrane component annotations. The significant genes had promoters enriched for HOXD12, HOXC13, and RREB-1 protein transcription factor binding sites. MuRF1 Tg + RV differentially expressed 150 genes in response to CH. Analysis of the top 45 genes (> 3-fold or < - 3-fold) revealed significant associations with oxidoreductase-metabolic, glycoprotein-transmembrane-integral proteins, and alternative splicing/splice variant annotations. The significant genes were enriched for promoters with ZIC1 protein transcription factor binding sites. CONCLUSIONS: The differentially expressed genes in MuRF1-/- and MuRF1 Tg + RV after CH have common functional annotations related to oxidoreductase (including antioxidant) and transmembrane component functions. Moreover, the functionally-enhanced MuRF1-/- hearts regulate genes related to transcription, homeobox proteins, and kinases/phosphorylation. These studies also reveal potential indirect effects of MuRF1 through regulating Rreb-1, and they reveal mechanisms by which MuRF1 may transcriptionally regulate anti-oxidant systems in the face of right heart failure.
Parametric amplifier for Bell measurement in continuous-variable quantum state teleportation
(American Physical Society, 2020-09) Chen, Xin; Ou, Z. Y.; Physics, School of Science
A parametric amplifier is in essence a linear four-port device, which couples and linearly mixes two inputs before amplifying and sending them to two output ports. Here we show that for quadrature-phase amplitudes, a parametric amplifier can replace beam splitters to play the role of the mixer. We apply this idea to a continuous-variable quantum state teleportation scheme in which a parametric amplifier replaces a beam splitter in the Bell measurement. We show that this scheme is loss tolerant in the Bell measurement process and thus demonstrate the advantage of the parametric amplifier over the beam splitter in the applications in quantum measurement.
USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer
(Springer Nature, 2022-09-26) Shi, Dongni; Wu, Xianqiu; Jian, Yunting; Wang, Junye; Huang, Chengmei; Mo, Shuang; Li, Yue; Li, Fengtian; Zhang, Chao; Zhang, Dongsheng; Zhang, Huizhong; Huang, Huilin; Chen, Xin; Wang, Y. Alan; Lin, Chuyong; Liu, Guozhen; Song, Libing; Liao, Wenting; Medicine, School of Medicine
Indoleamine 2,3 dioxygenase 1 (IDO1) is an attractive target for cancer immunotherapy. However, IDO1 inhibitors have shown disappointing therapeutic efficacy in clinical trials, mainly because of the activation of the aryl hydrocarbon receptor (AhR). Here, we show a post-transcriptional regulatory mechanism of IDO1 regulated by a proteasome-associated deubiquitinating enzyme, USP14, in colorectal cancer (CRC). Overexpression of USP14 promotes tryptophan metabolism and T-cell dysfunction by stabilizing the IDO1 protein. Knockdown of USP14 or pharmacological targeting of USP14 decreases IDO1 expression, reverses suppression of cytotoxic T cells, and increases responsiveness to anti-PD-1 in a MC38 syngeneic mouse model. Importantly, suppression of USP14 has no effects on AhR activation induced by the IDO1 inhibitor. These findings highlight a relevant role of USP14 in post-translational regulation of IDO1 and in the suppression of antitumor immunity, suggesting that inhibition of USP14 may represent a promising strategy for CRC immunotherapy.

Browsing by Author "Chen, Xin"

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