Professional Education

  • Doctor of Philosophy, University of California Merced (2016)
  • Master of Science, Chang Gung University (2009)
  • Bachelor of Science, Chang Gung University (2008)

Stanford Advisors


All Publications

  • Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense JOURNAL OF IMMUNOLOGY Hung, S., Hou, T., Jiang, W., Wang, N., Qiao, S., Chow, I., Liu, X., van der Burg, S. H., Koelle, D. M., Kwok, W. W., Sollid, L. M., Mellins, E. D. 2019; 202 (9): 2558?69
  • Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense. Journal of immunology (Baltimore, Md. : 1950) Hung, S., Hou, T., Jiang, W., Wang, N., Qiao, S., Chow, I., Liu, X., van der Burg, S. H., Koelle, D. M., Kwok, W. W., Sollid, L. M., Mellins, E. D. 2019


    We have reported that the major histocompatibility molecule HLA-DQ2 (DQA1*05:01/DQB1*02:01) (DQ2) is relatively resistant to HLA-DM (DM), a peptide exchange catalyst for MHC class II. In this study, we analyzed the role of DQ2/DM interaction in the generation of DQ2-restricted gliadin epitopes, relevant to celiac disease, or DQ2-restricted viral epitopes, relevant to host defense. We used paired human APC, differing in DM expression (DMnull versus DMhigh) or differing by expression of wild-type DQ2, versus a DM-susceptible, DQ2 point mutant DQ2alpha+53G. The APC pairs were compared for their ability to stimulate human CD4+ T cell clones. Despite higher DQ2 levels, DMhigh APC attenuated T cell responses compared with DMnull APC after intracellular generation of four tested gliadin epitopes. DMhigh APC expressing the DQ2alpha+53G mutant further suppressed these gliadin-mediated responses. The gliadin epitopes were found to have moderate affinity for DQ2, and even lower affinity for the DQ2 mutant, consistent with DM suppression of their presentation. In contrast, DMhigh APC significantly promoted the presentation of DQ2-restricted epitopes derived intracellularly from inactivated HSV type 2, influenza hemagglutinin, and human papillomavirus E7 protein. When extracellular peptide epitopes were used as Ag, the DQ2 surface levels and peptide affinity were the major regulators of T cell responses. The differential effect of DM on stimulation of the two groups of T cell clones implies differences in DQ2 presentation pathways associated with nonpathogen- and pathogen-derived Ags in vivo.

    View details for PubMedID 30926644

  • Citrullinated Peptide Epitope Targets Therapeutic Nanoparticles to Human Neutrophils. Bioconjugate chemistry Khatri, S., Hansen, J., Mendes, A. C., Chronakis, I. S., Hung, S. C., Mellins, E. D., Astakhova, K. 2019


    Multiple drugs have been proposed for reducing harsh symptoms of human rheumatic diseases. However, a targeted therapy with mild to no side effects is still missing. In this study, we have prepared and tested a series of therapeutic nanoparticles for specific targeting of human neutrophils associated with rheumatoid arthritis. In doing this, a series of citrullinated peptide epitopes derived from human proteins, fibrinogen, vimentin, and histone 3, were screened with regard to specific recognition of neutrophils. The most potent epitope proved to be a mutated fragment of an alpha chain in human fibrinogen. Next, a straightforward synthetic strategy was developed for nanoparticles decorated with this citrullinated peptide epitope and an antisense oligonucleotide targeting disease associated microRNA miR-125b-5p. Our study shows that the nanoparticles specifically recognize neutrophils and knock down miR-125b-5p, with no apparent toxicity to human cells. In contrast to organic dendrimers, chitosan-hyaluronic acid formulations do not activate human innate immune response. Our data proves that the strategy we report herein is effective in developing peptide epitopes for decorating delivery vehicles bearing biological drugs, targeted to a specific cell type.

    View details for DOI 10.1021/acs.bioconjchem.9b00518

    View details for PubMedID 31524379

  • NLRX1 modulates differentially NLRP3 inflammasome activation and NF-kappa B signaling during Fusobacterium nucleatum infection MICROBES AND INFECTION Hung, S., Huang, P., Coutinho Almeida-da-Silva, C., Atanasova, K. R., Yilmaz, O., Ojcius, D. M. 2018; 20 (9-10): 615?25


    NOD-like receptors (NLRs) play a large role in regulation of host innate immunity, yet their role in periodontitis remains to be defined. NLRX1, a member of the NLR family that localizes to mitochondria, enhances mitochondrial ROS (mROS) generation. mROS can activate the NLRP3 inflammasome, yet the role of NLRX1 in NLRP3 inflammasome activation has not been examined. In this study, we revealed the mechanism by which NLRX1 positively regulates ATP-induced NLRP3 inflammasome activation through mROS in gingival epithelial cells (GECs). We found that depletion of NLRX1 by shRNA attenuated ATP-induced mROS generation and redistribution of the NLRP3 inflammasome adaptor protein, ASC. Furthermore, depletion of NLRX1 inhibited Fusobacterium nucleatum infection-activated caspase-1, suggesting that it also inhibits the NLRP3 inflammasome. Conversely, NLRX1 also acted as a negative regulator of NF-?B signaling and IL-8 expression. Thus, NLRX1 stimulates detection of the pathogen F. nucleatum via the inflammasome, while dampening cytokine production. We expect that commensals should not activate the inflammasome, and NLRX1 should decrease their ability to stimulate expression of pro-inflammatory cytokines such as IL-8. Therefore, NLRX1 may act as a potential switch with regards to anti-microbial responses in healthy or diseased states in the oral cavity.

    View details for DOI 10.1016/j.micinf.2017.09.014

    View details for Web of Science ID 000450315700024

    View details for PubMedID 29024797

    View details for PubMedCentralID PMC5891395

  • Single-walled carbon nanotubes target neutrophils and Ly-6C(hi) monocytes and localize to joints in murine models of arthritis Hung, S., Rajasekaran, N., Zhu, S., Ma, Z., Ghosn, E., Mellins, E. D. AMER ASSOC IMMUNOLOGISTS. 2018
  • The Other Function: Class II-Restricted Antigen Presentation by B Cells FRONTIERS IN IMMUNOLOGY Adler, L. N., Jiang, W., Bhamidipati, K., Millican, M., Macaubas, C., Hung, S., Mellins, E. D. 2017; 8


    Mature B lymphocytes (B cells) recognize antigens using their B cell receptor (BCR) and are activated to become antibody-producing cells. In addition, and integral to the development of a high-affinity antibodies, B cells utilize the specialized major histocompatibility complex class II (MHCII) antigen presentation pathway to process BCR-bound and internalized protein antigens and present selected peptides in complex with MHCII to CD4+ T cells. This interaction influences the fate of both types of lymphocytes and shapes immune outcomes. Specific, effective, and optimally timed antigen presentation by B cells requires well-controlled intracellular machinery, often regulated by the combined effects of several molecular events. Here, we delineate and summarize these events in four steps along the antigen presentation pathway: (1) antigen capture and uptake by B cells; (2) intersection of internalized antigen/BCRs complexes with MHCII in peptide-loading compartments; (3) generation and regulation of MHCII/peptide complexes; and (4) exocytic transport for presentation of MHCII/peptide complexes at the surface of B cells. Finally, we discuss modulation of the MHCII presentation pathway across B cell development and maturation to effector cells, with an emphasis on the shaping of the MHCII/peptide repertoire by two key antigen presentation regulators in B cells: HLA-DM and HLA-DO.

    View details for DOI 10.3389/fimmu.2017.00319

    View details for Web of Science ID 000397144900001

    View details for PubMedID 28386257

  • Fusobacterium nucleatum infection of gingival epithelial cells leads to NLRP3 inflammasome-dependent secretion of IL-1 and the danger signals ASC and HMGB1 CELLULAR MICROBIOLOGY Bui, F. Q., Johnson, L., Roberts, J., Hung, S., Lee, J., Atanasova, K. R., Huang, P., Yilmaz, O., Ojcius, D. M. 2016; 18 (7): 970-981


    Fusobacterium nucleatum is an invasive anaerobic bacterium that is associated with periodontal disease. Previous studies have focused on virulence factors produced by F. nucleatum, but early recognition of the pathogen by the immune system remains poorly understood. Although an inflammasome in gingival epithelial cells (GECs) can be stimulated by danger-associated molecular patterns (DAMPs) (also known as danger signals) such as ATP, inflammasome activation by this periodontal pathogen has yet to be described in these cells. This study therefore examines the effects of F. nucleatum infection on pro-inflammatory cytokine expression and inflammasome activation in GECs. Our results indicate that infection induces translocation of NF-?B into the nucleus, resulting in cytokine gene expression. In addition, infection activates the NLRP3 inflammasome, which in turn activates caspase-1 and stimulates secretion of mature IL-1?. Unlike other pathogens studied until now, F. nucleatum activates the inflammasome in GECs in the absence of exogenous DAMPs such as ATP. Finally, infection promotes release of other DAMPs that mediate inflammation, such as high-mobility group box 1 protein and apoptosis-associated speck-like protein, with a similar time-course as caspase-1 activation. Thus, F. nucleatum expresses the pathogen-associated molecular patterns necessary to activate NF-?B and also provides an endogenous DAMP to stimulate the inflammasome and further amplify inflammation through secretion of secondary DAMPs.

    View details for DOI 10.1111/cmi.12560

    View details for Web of Science ID 000378718100006

    View details for PubMedID 26687842

  • Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase MICROBES AND INFECTION Johnson, L., Atanasova, K. R., Bui, P. Q., Lee, J., Hung, S., Yilmaz, O., Ojcius, D. M. 2015; 17 (5): 369-377


    Many intracellular pathogens evade the innate immune response in order to survive and proliferate within infected cells. We show that Porphyromonas gingivalis, an intracellular opportunistic pathogen, uses a nucleoside-diphosphate kinase (NDK) homolog to inhibit innate immune responses due to stimulation by extracellular ATP, which acts as a danger signal that binds to P2X7 receptors and induces activation of an inflammasome and caspase-1. Thus, infection of gingival epithelial cells (GECs) with wild-type P. gingivalis results in inhibition of ATP-induced caspase-1 activation. However, ndk-deficient P. gingivalis is less effective than wild-type P. gingivalis in reducing ATP-mediated caspase-1 activation and secretion of the pro-inflammatory cytokine, IL-1?, from infected GECs. Furthermore, P. gingivalis NDK modulates release of high-mobility group protein B1 (HMGB1), a pro-inflammatory danger signal, which remains associated with chromatin in healthy cells. Unexpectedly, infection with either wild-type or ndk-deficient P. gingivalis causes release of HMGB1 from the nucleus to the cytosol. But HMGB1 is released to the extracellular space when uninfected GECs are further stimulated with ATP, and there is more HMGB1 released from the cells when ATP-treated cells are infected with ndk-deficient mutant than wild-type P. gingivalis. Our results reveal that NDK plays a significant role in inhibiting P2X7-dependent inflammasome activation and HMGB1 release from infected GECs.

    View details for DOI 10.1016/j.micinf.2015.03.010

    View details for Web of Science ID 000355037600007

    View details for PubMedID 25828169

  • N-(1-Pyrenyl) Maleimide Induces Bak Oligomerization and Mitochondrial Dysfunction in Jurkat Cells BIOMED RESEARCH INTERNATIONAL Huang, P., Hung, S., Pao, C., Wang, T. V. 2015


    N-(1-pyrenyl) maleimide (NPM) is a fluorescent reagent that is frequently used as a derivatization agent for the detection of thio-containing compounds. NPM has been shown to display a great differential cytotoxicity against hematopoietic cancer cells. In this study, the molecular mechanism by which NPM induces apoptosis was examined. Here, we show that treatment of Jurkat cells with NPM leads to Bak oligomerization, loss of mitochondrial membrane potential (??m), and release of cytochrome C from mitochondria to cytosol. Induction of Bak oligomerization appears to play a critical role in NPM-induced apoptosis, as downregulation of Bak by shRNA significantly prevented NPM-induced apoptosis. Inhibition of caspase 8 by Z-IETD-FMK and/or depletion of Bid did not affect NPM-induced oligomerization of Bak. Taken together, these results suggest that NPM-induced apoptosis is mediated through a pathway that is independent of caspase-8 activation.

    View details for DOI 10.1155/2015/798489

    View details for Web of Science ID 000348296900001

    View details for PubMedID 25632401

  • P2X(4) Assembles with P2X(7) and Pannexin-1 in Gingival Epithelial Cells and Modulates ATP-induced Reactive Oxygen Species Production and Inflammasome Activation PLOS ONE Hung, S., Choi, C. H., Said-Sadier, N., Johnson, L., Atanasova, K. R., Sellami, H., Yilmaz, O., Ojcius, D. M. 2013; 8 (7)


    We have previously reported that Porphyromonas gingivalis infection of gingival epithelial cells (GEC) requires an exogenous danger signal such as ATP to activate an inflammasome and caspase-1, thereby inducing secretion of interleukin (IL)-1?. Stimulation with extracellular ATP also stimulates production of reactive oxygen species (ROS) in GEC. However, the mechanism by which ROS is generated in response to ATP, and the role that different purinergic receptors may play in inflammasome activation, is still unclear. In this study, we revealed that the purinergic receptor P2X(4) is assembled with the receptor P2X(7) and its associated pore, pannexin-1. ATP induces ROS production through a complex consisting of the P2X(4), P2X(7), and pannexin-1. P2X(7)-mediated ROS production can activate the NLRP3 inflammasome and caspase-1. Furthermore, separate depletion or inhibition of P2X(4), P2X(7), or pannexin-1 complex blocks IL-1? secretion in P. gingivalis-infected GEC following ATP treatment. However, activation via P2X(4) alone induces ROS generation but not inflammasome activation. These results suggest that ROS is generated through stimulation of a P2X(4)/P2X(7)/pannexin-1 complex, and reveal an unexpected role for P2X(4), which acts as a positive regulator of inflammasome activation during microbial infection.

    View details for DOI 10.1371/journal.pone.0070210

    View details for Web of Science ID 000322433300094

    View details for PubMedID 23936165

  • Telomeric DNA-binding activities of heterogeneous nuclear ribonucleoprotein A3 in vitro and in vivo BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH Huang, P., Hung, S., Wang, T. V. 2010; 1803 (10): 1164-1174


    Telomeres are dynamic DNA-protein complexes that protect the ends of linear chromosome. Telomere-binding proteins play crucial role in the maintenance of telomeres. HnRNP A3 has been shown recently to bind specifically to single-stranded telomeric DNA in vitro, although its in vivo telomere function remains unknown. In this study, the DNA-binding properties of hnRNP A3 in vitro as well as its putative role of telomere maintenance in vivo were investigated. The minimal sequence for hnRNP A3 binding to DNA was determined as an undecamer with the following consensus sequence 5'-[T/C]AG[G/T]NN[T/C]AG[G/T]N-3'. Confocal microscopy and chromatin-immunoprecipitation (ChIP) analyses showed that hnRNP A3 is associated with telomere in vivo. Knocking-down the expression of hnRNP A3 had no effect on telomere length maintenance and did not affect cell proliferation. In contrast, overexpression of hnRNP A3 resulted in the production of steady-state short telomeres in OECM1 cells. These results suggest that hnRNP A3 is associated with telomere in vivo and acts as a negative regulator of telomere length maintenance.

    View details for DOI 10.1016/j.bbamcr.2010.06.003

    View details for Web of Science ID 000281920200005

    View details for PubMedID 20600361

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