IU Indianapolis ScholarWorks :: Browsing by Author "Wang, Qun"

Browsing by Author "Wang, Qun"

Now showing 1 - 9 of 9

The 2022 Global Philanthropy Environment Index China
(IU Lilly Family School of Philanthropy, 2022-03-30) Wang, Qun
FOXP3 exon 2 controls Treg stability and autoimmunity
(American Association for the Advancement of Science, 2022) Du, Jianguang; Wang, Qun; Yang, Shuangshuang; Chen, Si; Fu, Yongyao; Spath, Sabine; Domeier, Phillip; Hagin, David; Anover-Sombke, Stephanie; Haouili, Maya; Liu, Sheng; Wan, Jun; Han, Lei; Liu, Juli; Yang, Lei; Sangani, Neel; Li, Yujing; Lu, Xiongbin; Janga, Sarath Chandra; Kaplan, Mark H.; Torgerson, Troy R.; Ziegler, Steven F.; Zhou, Baohua; Pediatrics, School of Medicine
Differing from the mouse Foxp3 gene that encodes only one protein product, human FOXP3 encodes two major isoforms through alternative splicing-a longer isoform (FOXP3 FL) containing all the coding exons and a shorter isoform lacking the amino acids encoded by exon 2 (FOXP3 ΔE2). The two isoforms are naturally expressed in humans, yet their differences in controlling regulatory T cell phenotype and functionality remain unclear. In this study, we show that patients expressing only the shorter isoform fail to maintain self-tolerance and develop immunodeficiency, polyendocrinopathy, and enteropathy X-linked (IPEX) syndrome. Mice with Foxp3 exon 2 deletion have excessive follicular helper T (TFH) and germinal center B (GC B) cell responses, and develop systemic autoimmune disease with anti-dsDNA and antinuclear autoantibody production, as well as immune complex glomerulonephritis. Despite having normal suppressive function in in vitro assays, regulatory T cells expressing FOXP3 ΔE2 are unstable and sufficient to induce autoimmunity when transferred into Tcrb-deficient mice. Mechanistically, the FOXP3 ΔE2 isoform allows increased expression of selected cytokines, but decreased expression of a set of positive regulators of Foxp3 without altered binding to these gene loci. These findings uncover indispensable functions of the FOXP3 exon 2 region, highlighting a role in regulating a transcriptional program that maintains Treg stability and immune homeostasis.
FOXP3 interacts with hnRNPF to modulate pre-mRNA alternative splicing
(American Society for Biochemistry and Molecular Biology, 2018-06-29) Du, Jianguang; Wang, Qun; Ziegler, Steven F.; Zhou, Baohua; Microbiology and Immunology, School of Medicine
FOXP3 promotes the development and function of regulatory T cells mainly through regulating the transcription of target genes. RNA alternative splicing has been implicated in a wide range of physiological and pathophysiological processes. We report here that FOXP3 associates with heterogeneous nuclear ribonucleoprotein (hnRNP) F through the exon 2-encoded region of FOXP3 and the second quasi-RNA recognition motif (qRRM) of hnRNPF. FOXP3 represses the ability of hnRNPF to bind to its target pre-mRNA and thus modulates RNA alternative splicing. Furthermore, overexpression of mouse hnRNPF in in vitro-differentiated regulatory T cells (Tregs) reduced their suppressive function. Thus, our studies identify a novel mechanism by which FOXP3 regulates mRNA alternative splicing to modulate the function of regulatory T cells.
Lunasin alleviates allergic airway inflammation while increases antigen-specific Tregs
(PLoS, 2015-02-03) Yang, Xiaowei; Zhu, Jingjing; Tung, Chun-Yu; Gardiner, Gail; Wang, Qun; Chang, Hua-Chen; Zhou, Baohua; Department of Pediatrics, IU School of Medicine
Lunasin is a naturally occurring peptide isolated from soybeans and has been explored in cancer treatment. Lunasin inhibits NF-κB activation and thus pro-inflammatory cytokine and mediator production in macrophages. In this study we demonstrate that lunasin can effectively suppress allergic airway inflammation in two murine models of asthma. In an OVA+Alum sensitization model, intranasal lunasin treatment at the time of OVA challenges significantly reduced total cells counts in bronchoalveolar lavage (BAL) fluid and eosinophilia, peribronchiolar inflammatory infiltration, goblet cell metaplasia and airway IL-4 production. In an OVA+LPS intranasal sensitization model, lunasin treatment either at the time of sensitization or challenge has similar effects in suppress allergic airway inflammation including significantly reduced total cell and eosinophil counts in BAL fluid, inflammatory gene Fizz1 expression in the lung, and IL-4 production by OVA re-stimulated cells from mediastinal lymph nodes. We further show that intranasal instillation of OVA+lunasin significantly increases OVA-specific regulatory T cell (Treg) accumulation in the lung comparing to OVA only treatment. Taken together, our results suggest lunasin as an anti-inflammatory agent can be potentially used in asthma therapy or as an adjuvant to enhance the induction of antigen-specific Tregs and thus boost the efficacy of allergy immunotherapy.
Reliable detection of subchromosomal deletions and duplications using cell-based noninvasive prenatal testing
(Wiley, 2018-10-25) Vossaert, Liesbeth; Wang, Qun; Salman, Roseen; Zhuo, Xinming; Qu, Chunjing; Henke, David; Seubert, Ron; Chow, Jennifer; U'ren, Lance; Enright, Brennan; Stilwell, Jackie; Kaldjian, Eric; Yang, Yaping; Shaw, Chad; Levy, Brynn; Wapner, Ronald; Breman, Amy; Veyver, Ignatia Van den; Beaudet, Arthur; Medical and Molecular Genetics, School of Medicine
Objective To gather additional data on the ability to detect subchromosomal abnormalities of various sizes in single fetal cells isolated from maternal blood, using low-coverage shotgun next-generation sequencing for cell-based noninvasive prenatal testing (NIPT). Method Fetal trophoblasts were recovered from approximately 30 mL of maternal blood using maternal white blood cell depletion, density-based cell separation, immunofluorescence staining, and high-resolution scanning. These trophoblastic cells were picked as single cells and underwent whole genome amplification for subsequent genome-wide copy number analysis and genotyping to confirm the fetal origin of the cells. Results Applying our fetal cell isolation method to a series of 125 maternal blood samples, we detected on average 4.17 putative fetal cells/sample. The series included 15 cases with clinically diagnosed fetal aneuploidies and five cases with subchromosomal abnormalities. This method was capable of detecting findings that were 1 to 2 Mb in size, and all were concordant with the microarray or karyotype data obtained on a fetal sample. A minority of fetal cells showed evidence of genome degradation likely related to apoptosis. Conclusion We demonstrate that this cell-based NIPT method has the capacity to reliably diagnose fetal chromosomal abnormalities down to 1 to 2 Mb in size.
The research infrastructure of Chinese foundations, a database for Chinese civil society studies
(Nature Publishing group, 2017-07-25) Ma, Ji; Wang, Qun; Dong, Chao; Li, Huafang; Lilly Family School of Philanthropy
This paper provides technical details and user guidance on the Research Infrastructure of Chinese Foundations (RICF), a database of Chinese foundations, civil society, and social development in general. The structure of the RICF is deliberately designed and normalized according to the Three Normal Forms. The database schema consists of three major themes: foundations’ basic organizational profile (i.e., basic profile, board member, supervisor, staff, and related party tables), program information (i.e., program information, major program, program relationship, and major recipient tables), and financial information (i.e., financial position, financial activities, cash flow, activity overview, and large donation tables). The RICF’s data quality can be measured by four criteria: data source reputation and credibility, completeness, accuracy, and timeliness. Data records are properly versioned, allowing verification and replication for research purposes.
Society for Translational Medicine Expert consensus on the selection of surgical approaches in the management of thoracic esophageal carcinoma
(AME Publishing Company, 2019-01) Mao, Yousheng; Yu, Zhentao; You, Bin; Fang, Wentao; Badgwell, Brian; Berry, Mark F.; Ceppa, DuyKhanh P.; Chen, Chun; Chen, Haiquan; Cuesta, Miguel A.; D’Journo, Xavier Benoit; Eslick, Guy D.; Fu, Jianhua; Fu, Xiangning; Gao, Shugeng; He, Jianxing; He, Jie; Huang, Yunchao; Jiang, Gening; Jiang, Zhongmin; Kim, Jae Y.; Li, Danqing; Li, Hui; Li, Shanqing; Liu, Deruo; Liu, Lunxu; Liu, Yongyu; Li, Xiaofei; Li, Yin; Mao, Weimin; Molena, Daniela; Morse, Christopher R.; Novoa, Nuria M.; Tan, Lijie; Tan, Qunyou; Toker, Alper; Tong, Ti; Wang, Qun; Weksler, Benny; Xu, Lin; Xu, Shidong; Yan, Tiansheng; Zhang, Lanjun; Zhang, Xingyi; Zhang, Xun; Zhang, Zhu; Zhi, Xiuyi; Zhou, Qinghua; Department of Surgery, Indiana University School of Medicine
Use of amplicon-based sequencing for testing fetal identity and monogenic traits with Single Circulating Trophoblast (SCT) as one form of cell-based NIPT
(PLOS, 2021-04-15) Zhuo, Xinming; Wang, Qun; Vossaert, Liesbeth; Salman, Roseen; Kim, Adriel; Van den Veyver, Ignatia; Breman, Amy; Beaudet, Arthur; Medical and Molecular Genetics, School of Medicine
A major challenge for cell-based non-invasive prenatal testing (NIPT) is to distinguish individual presumptive fetal cells from maternal cells in female pregnancies. We have sought a rapid, robust, versatile, and low-cost next-generation sequencing method to facilitate this process. Toward this goal, single isolated cells underwent whole genome amplification prior to genotyping. Multiple highly polymorphic genomic regions (including HLA-A and HLA-B) with 10-20 very informative single nucleotide polymorphisms (SNPs) within a 200 bp interval were amplified with a modified method based on other publications. To enhance the power of cell identification, approximately 40 Human Identification SNP (Applied Biosystems) test amplicons were also utilized. Using SNP results to compare to sex chromosome data from NGS as a reliable standard, the true positive rate for genotyping was 83.4%, true negative 6.6%, false positive 3.3%, and false negative 6.6%. These results would not be sufficient for clinical diagnosis, but they demonstrate the general validity of the approach and suggest that deeper genotyping of single cells could be completely reliable. A paternal DNA sample is not required using this method. The assay also successfully detected pathogenic variants causing Tay Sachs disease, cystic fibrosis, and hemoglobinopathies in single lymphoblastoid cells, and disease-causing variants in three cell-based NIPT cases. This method could be applicable for any monogenic diagnosis.
Validation Studies for Single Circulating Trophoblast Genetic Testing as a Form of Noninvasive Prenatal Diagnosis
(Elsevier, 2019-12-05) Vossaert, Liesbeth; Wang, Qun; Salman, Roseen; McCombs, Anne K.; Patel, Vipulkumar; Qu, Chunjing; Mancini, Michael A.; Edwards, Dean P.; Malovannaya, Anna; Liu, Pengfei; Shaw, Chad A.; Levy, Brynn; Wapner, Ronald J.; Bi, Weimin; Breman, Amy M.; Van den Veyver, Ignatia B.; Beaudet, Arthur L.; Medical and Molecular Genetics, School of Medicine
It has long been appreciated that genetic analysis of fetal or trophoblast cells in maternal blood could revolutionize prenatal diagnosis. We implemented a protocol for single circulating trophoblast (SCT) testing using positive selection by magnetic-activated cell sorting and single-cell low-coverage whole-genome sequencing to detect fetal aneuploidies and copy-number variants (CNVs) at ∼1 Mb resolution. In 95 validation cases, we identified on average 0.20 putative trophoblasts/mL, of which 55% were of high quality and scorable for both aneuploidy and CNVs. We emphasize the importance of analyzing individual cells because some cells are apoptotic, in S-phase, or otherwise of poor quality. When two or more high-quality trophoblast cells were available for singleton pregnancies, there was complete concordance between all trophoblasts unless there was evidence of confined placental mosaicism. SCT results were highly concordant with available clinical data from chorionic villus sampling (CVS) or amniocentesis procedures. Although determining the exact sensitivity and specificity will require more data, this study further supports the potential for SCT testing to become a diagnostic prenatal test.

Browsing by Author "Wang, Qun"

Results Per Page

Sort Options