Jennifer Zhang

Duke University

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Simone Degan

Duke University

Yingai J. Jin

Duke University

Russell P. Hall

Duke University

Jane Y. Jin

Duke Medical Center

Shiying Tao

Stanford University

Warren S. Warren

Duke University

Detlev Erdmann

Duke Medical Center

Paul A. Khavari

Stanford University

Paula Miliani de Marval

Charles River Laboratories (United States)

Jesse W. Wilson

Colorado State University

Cooperative Institutions

European Organization for Nuclear Research

327

Centro Brasileiro de Pesquisas Físicas

315

Duke University

174

Centre National de la Recherche Scientifique

163

University of Chinese Academy of Sciences

158

École Polytechnique Fédérale de Lausanne

Tsinghua University

Duke Medical Center

Peking University

Duke University Hospital

121

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c-Jun Promotes whereas JunB Inhibits Epidermal Neoplasia

Journal of Investigative Dermatology (2011)

Jane Y. Jin Hengning Ke Russell P. Hall Jennifer Zhang

JUNB

AP-1 transcription factor

c-jun

10.1038/jid.2011.1

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Citations (38)

Diroximel fumarate acts through Nrf2 to attenuate methylglyoxal-induced nociception in mice and decrease ISR activation in DRG neurons

Muhammad Saad Yousuf Marisol Mancilla Moreno Brodie J Woodall Vikram Thakur Jiahe Li

Diabetic neuropathic pain is associated with elevated plasma levels of methylglyoxal (MGO). MGO is a metabolite of glycolysis that causes pain hypersensitivity in mice by stimulating the phosphorylation of eukaryotic initiation factor 2α (p-eIF2α) and subsequently activating the integrated stress response (ISR). We first established that Zucker Diabetic Fatty (ZDF) rats have enhanced MGO signaling, engage the ISR, and develop pain hypersensitivity. Since nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins that neutralize MGO, we hypothesized that fumarates, like diroximel fumarate (DRF), will stimulate Nrf2 signaling, and prevent MGO-induced ISR and pain hypersensitivity. DRF (100 mg/kg) treated animals were protected from developing MGO (20 ng) induced mechanical and cold hypersensitivity. Mechanistically, DRF treatment protected against MGO-induced increase in p-eIF2α levels in the sciatic nerve and reduced loss of intraepidermal nerve fiber (IENF) density. Using Nrf2-knockout mice we demonstrate that Nrf2 is necessary for the anti-nociceptive effects of DRF. Co-treatment of MGO (1µM) with monomethyl fumarate (MMF) (10, 20, 50 µM), the active metabolite of DRF, prevented the ISR in both mouse and human DRG neurons. Our data show that targeting Nrf2 with DRF is a strategy to potentially alleviate pain associated with elevated MGO levels.

10.2337/figshare.28436780

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Corrigendum to “PRRT2 frameshift mutation reduces its mRNA stability resulting loss of function in paroxysmal kinesigenic dyskinesia”

Biochemical and Biophysical Research Communications (2020)

Yongcheng Pan Qiong Liu Jennifer Zhang Yang Yang Yun Tian

Paroxysmal dyskinesia

10.1016/j.bbrc.2020.02.159

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BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization

Cell Research (2010)

Hengning Ke Vandy I. Parron Jeff Reece Jennifer Zhang Steven K. Akiyama

Gelsolin

Actin remodeling

10.1038/cr.2010.21

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Citations (41)

The Pathogenic Role of NLRP3 Inflammasome Activation in Inflammatory Bowel Diseases of Both Mice and Humans

Journal of Crohn s and Colitis (2016)

Ling Liu Ying Dong Mei Ye Shi Jin Jianbo Yang

NLRP3 inflammasome is known to be involved in inflammatory bowel diseases. However, it is controversial whether it is pathogenic or beneficial. This study evaluated the roles of NLRP3 inflammasome in the pathogenesis of inflammatory bowel disease in IL-10-/- mice and humans. NLRP3 inflammasome in colonic mucosa, macrophages, and colonic epithelial cells were analysed by western blotting. The NLRP3 inflammasome components were studied by sucrose density gradient fractionation, chemical cross-linking, and co-immunoprecipitation. The role of NLPR3 inflammasome in the pathogenesis of colitis was extensively evaluated in IL-10-/- mice, using a specific NLPR3 inflammasome inhibitor glyburide. NLRP3 inflammasome was upregulated in colonic mucosa of both IL-10-/- mice and Crohn's patients. NLRP3 inflammasome activity in IL-10-/- mice was elevated prior to colitis onset; it progressively increased as disease worsened and peaked as macroscopic disease emerged. NLRP3 inflammasome was found in both intestinal epithelial cells and colonic macrophages, as a large complex with a molecular weight of ≥ 360 kDa in size. In the absence of IL-10, NLRP3 inflammasome was spontaneously active and more robustly responsive when activated by LPS and nigericin. Glyburide markedly suppressed NLRP3 inflammasome expression/activation in IL-10-/- mice, leading to not only alleviation of ongoing colitis but also prevention/delay of disease onset. Glyburide also effectively inhibited the release of proinflammatory cytokines/chemokines by mucosal explants from Crohn's patients. Abnormal activation of NLRP3 inflammasome plays a major pathogenic role in the development of chronic colitis in IL-10-/- mice and humans. Glyburide, an FDA-approved drug, may have great potential in the management of inflammatory bowel diseases.

Inflammatory Bowel Diseases

10.1093/ecco-jcc/jjw219

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Citations (164)

3D Printing of Polytetrafluoroethylene Hollow Needles for Medical Applications

JOM (2021)

Roger Sachan Andrew Sachan Junqi Lu Detlev Erdmann Jennifer Zhang

Polytetrafluoroethylene

Penetration (warfare)

10.1007/s11837-021-04978-3

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Citations (3)

Abstract 2919: Targeting regulatory T cells to boost immunity against melanoma

Cancer Research (2024)

Wanying Miao Yingai J. Jin Vaibhav Jain Simon G. Gregory Jennifer Zhang

Abstract Tumor-infiltrated regulatory T-cells (Treg) restrict the function of effector T-cells and thereby promote tumor growth. Disrupting the immunosuppression of Treg cells presents an attractive strategy for cancer immunotherapy; However, the risk of autoimmunity, resulting from systemic Treg depletion, limits its therapeutic effectiveness. Here, we show that genetic depletion of Ube2n in Treg cells inhibits tumor growth which is correlated with a markedly enhanced infiltration of cytotoxic immune cells. Notably, the deletion of Ube2n in a fraction of Treg cells was sufficient to produce a long-lasting anti-tumor effect, without apparent systemic autoimmune responses. The antitumor effect persists following adoptive T-cell transfer to an otherwise immunodeficient mouse tumor model. Through flow cytometry, immunostaining and T-cell targeted single-cell sequencing analyses, we demonstrate that the loss of Ube2n dampens Treg suppressive function, as indicated by markedly increased numbers of cytotoxic CD8 T-cells in the tumor microenvironment (TME). Further, differentially expressed genes analyses show a downregulation of Mki67 and an upregulation of Ifng in Ube2n deficient Tregs, concomitant with amplification and activation of effector T-cells. Our findings uncover a hitherto unexplored role of Ube2n in orchestrating the differentiation and functions of Treg in TME, highlighting the therapeutic potential of targeting this pathway to enhance and reprogram anti-tumor immunity. Citation Format: Wanying Miao, Yingai J. Jin, Vaibhav Jain, Simon Gregory, Jennifer Y. Zhang. Targeting regulatory T cells to boost immunity against melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2919.

10.1158/1538-7445.am2024-2919

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Application of Patient-Specific iPSCs for Modelling and Treatment of X-Linked Cardiomyopathies

International Journal of Molecular Sciences (2021)

Jennifer Zhang Oscar Hou In Chou Yiu-Lam Tse Kwong‐Man Ng Hung‐Fat Tse

Inherited cardiomyopathies are among the major causes of heart failure and associated with significant mortality and morbidity. Currently, over 70 genes have been linked to the etiology of various forms of cardiomyopathy, some of which are X-linked. Due to the lack of appropriate cell and animal models, it has been difficult to model these X-linked cardiomyopathies. With the advancement of induced pluripotent stem cell (iPSC) technology, the ability to generate iPSC lines from patients with X-linked cardiomyopathy has facilitated in vitro modelling and drug testing for the condition. Nonetheless, due to the mosaicism of the X-chromosome inactivation, disease phenotypes of X-linked cardiomyopathy in heterozygous females are also usually more heterogeneous, with a broad spectrum of presentation. Recent advancements in iPSC procedures have enabled the isolation of cells with different lyonisation to generate isogenic disease and control cell lines. In this review, we will summarise the current strategies and examples of using an iPSC-based model to study different types of X-linked cardiomyopathy. The potential application of isogenic iPSC lines derived from a female patient with heterozygous Danon disease and drug screening will be demonstrated by our preliminary data. The limitations of an iPSC-derived cardiomyocyte-based platform will also be addressed.

10.3390/ijms22158132

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Citations (4)

Novel pyrrolyllactone and pyrrolyllactam indolinones as potent cyclin-Dependent kinase 2 inhibitors

Bioorganic & Medicinal Chemistry Letters (2003)

Xiaoyuan Li Ping Huang Jingrong Jean Cui Jennifer Zhang Cho Tang

10.1016/s0960-894x(03)00312-3

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Citations (31)

Data from UBE2N Promotes Melanoma Growth via MEK/FRA1/SOX10 Signaling

Anushka Dikshit Yingai J. Jin Simone Degan Ji-Hwan Hwang Matthew W. Foster

<div>AbstractUBE2N is a K63-specific ubiquitin conjugase linked to various immune disorders and cancer. Here, we demonstrate that UBE2N and its partners UBE2V1 and UBE2V2 are highly expressed in malignant melanoma. Silencing of UBE2N and its partners significantly decreased melanoma cell proliferation and subcutaneous tumor growth. This was accompanied by increased expression of E-cadherin, p16, and MC1R and decreased expression of melanoma malignancy markers including SOX10, Nestin, and ABCB5. Mass spectrometry–based phosphoproteomic analysis revealed that UBE2N loss resulted in distinct alterations to the signaling landscape: MEK/ERK signaling was impaired, FRA1 and SOX10 gene regulators were downregulated, and p53 and p16 tumor suppressors were upregulated. Similar to inhibition of UBE2N and MEK, silencing FRA1 decreased SOX10 expression and cell proliferation. Conversely, exogenous expression of active FRA1 increased pMEK and SOX10 expression, and restored anchorage-independent cell growth of cells with UBE2N loss. Systemic delivery of NSC697923, a small-molecule inhibitor of UBE2N, significantly decreased melanoma xenograft growth. These data indicate that UBE2N is a novel regulator of the MEK/FRA1/SOX10 signaling cascade and is indispensable for malignant melanoma growth. Our findings establish the basis for targeting UBE2N as a potential treatment strategy for melanoma.Significance: These findings identify ubiquitin conjugase UBE2N and its variant partners as novel regulators of MAPK signaling and potential therapeutic targets in melanoma. Cancer Res; 78(22); 6462–72. ©2018 AACR.</div>

SOX10

10.1158/0008-5472.c.6510647

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