About

Dr. Keren He is an Assistant Professor in the Department of Asian and Middle Eastern Studies at the University of North Carolina at Chapel Hill. She holds a Ph.D. from Stanford University and specializes in modern Chinese and Sinophone literature, media, and culture. Her research focuses on age and suicide studies, theorizing aging and suicide as resistant politics of living against the principles of developmentalism, which instrumentalize individual life courses for state and capital agendas. Her broader academic interests include Sinophone game studies and queer cultures.

Research topics

• Biology
• Virology
• Genetics
• Biochemistry
• Cell biology
• Immunology

Selected publications

• EXOC5/SEC10 attenuates antiviral IFN-I signaling by targeting STING1 for autophagic degradation

  Figshare · 2026-04-13

  articleOpen access

  EXOC5/SEC10, the central subunit of the exocyst complex, is crucial for the trafficking of secretory vesicles to the plasma membrane. However, its role in innate immunity and viral replication remains unclear. Here we demonstrate that EXOC5 acts as a negative regulator of DNA virus-triggered CGAS-STING1 signaling via targeting STING1. Mechanistically, EXOC5 facilitates the autophagic degradation of STING1 via K63-linked polyubiquitination at Lys224 and Lys338 by the E3 ligase TRIM56, which serves as a recognition signal for the cargo receptor SQSTM1/p62 (sequestosome 1). Furthermore, EXOC5 inhibits antiviral innate immunity and promotes viral replication via EXOC5-TRIM56-STING1-SQSTM1 signal transduction. More importantly, myeloid-specific deletion of <i>Exoc5</i> in mice improves survival and reduces viral load. In general, these findings revealed a negative feedback loop of type I interferon signaling through the EXOC5-TRIM56-STING1-SQSTM1 axis, which has the potential to serve as a new target for the development of antiviral therapeutics that regulate the host immune response. <b>Abbreviations:</b> BafA1: bafilomycin A1; BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; EXOC5/SEC10: exocyst complex component 5; HAdV-4: human adenovirus type 4; HSV-1: herpes simplex virus type 1; HT-DNA: herring testis deoxyribonucleic acid; IFN: interferon; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; PMs: peritoneal macrophages; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; VACV70: 70-mers of dsDNA representing the genome of vaccinia virus.

  PublisherDOI

• EXOC5/SEC10 attenuates antiviral IFN-I signaling by targeting STING1 for autophagic degradation

  Autophagy · 2026-04-13

  article

  BafA1: bafilomycin A1; BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; EXOC5/SEC10: exocyst complex component 5; HAdV-4: human adenovirus type 4; HSV-1: herpes simplex virus type 1; HT-DNA: herring testis deoxyribonucleic acid; IFN: interferon; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; PMs: peritoneal macrophages; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; VACV70: 70-mers of dsDNA representing the genome of vaccinia virus.

  PublisherDOI

• Sec8: a novel positive regulator of RIG-I in anti-RNA viral defense

  Cell Death and Disease · 2026-01-24

  articleOpen access

  Sec8, an exocyst complex subunit, is pivotal in facilitating the docking of exocytic vesicles to fusion sites on the plasma membrane. However, its involvement in the antiviral innate immune response and virus replication remains unclear. In this study, Sec8 is identified as a novel positive regulator of RIG-I, enhancing the IFN-I signaling response against RNA viruses both in vivo and in vitro. Additionally, Sec8 stabilizes RIG-I by inhibiting its ubiquitination and subsequent proteasome-mediated degradation. Mechanistically, STUB1 degrades RIG-I via K48-linked ubiquitination at Lys190, while Sec8 suppresses STUB1 mRNA by reducing the expression of p53 and competes with STUB1 for binding to RIG-I's CARD domain, thereby preventing STUB1-mediated RIG-I degradation. Importantly, Sec8-deficient mice were more susceptible to RNA virus infection compared to wild-type mice. These findings elucidate a mechanism that Sec8 positively regulates RIG-I in the antiviral innate immune response, offering insights for developing novel therapeutic strategies and targeted antiviral medications.

  PublisherOA PDFDOI

• EXOC5/SEC10 attenuates antiviral IFN-I signaling by targeting STING1 for autophagic degradation

  Figshare · 2026-04-13

  articleOpen access

  EXOC5/SEC10, the central subunit of the exocyst complex, is crucial for the trafficking of secretory vesicles to the plasma membrane. However, its role in innate immunity and viral replication remains unclear. Here we demonstrate that EXOC5 acts as a negative regulator of DNA virus-triggered CGAS-STING1 signaling via targeting STING1. Mechanistically, EXOC5 facilitates the autophagic degradation of STING1 via K63-linked polyubiquitination at Lys224 and Lys338 by the E3 ligase TRIM56, which serves as a recognition signal for the cargo receptor SQSTM1/p62 (sequestosome 1). Furthermore, EXOC5 inhibits antiviral innate immunity and promotes viral replication via EXOC5-TRIM56-STING1-SQSTM1 signal transduction. More importantly, myeloid-specific deletion of <i>Exoc5</i> in mice improves survival and reduces viral load. In general, these findings revealed a negative feedback loop of type I interferon signaling through the EXOC5-TRIM56-STING1-SQSTM1 axis, which has the potential to serve as a new target for the development of antiviral therapeutics that regulate the host immune response. <b>Abbreviations:</b> BafA1: bafilomycin A1; BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; EXOC5/SEC10: exocyst complex component 5; HAdV-4: human adenovirus type 4; HSV-1: herpes simplex virus type 1; HT-DNA: herring testis deoxyribonucleic acid; IFN: interferon; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; PMs: peritoneal macrophages; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; VACV70: 70-mers of dsDNA representing the genome of vaccinia virus.

  PublisherDOI

• Sec10 suppresses antiviral innate immune response by facilitating STUB1-mediated STAT1 degradation

  PLoS Pathogens · 2025-09-08 · 2 citations

  articleOpen accessCorresponding

  The exocyst complex is a heterooctameric protein complex, the individual components of the complex are thought to act on specific biological processes. However, the role of Sec10, the central subunit of the complex, in host defense and viral replication remains unclear. Here, we reported that Sec10 significantly impairs the activation of JAK-STAT signal pathway of type I IFN (IFN-I) response against both DNA- and RNA-viruses, and promotes viral replication, respectively. Mechanistically, Sec10 interacts with E3 ligase STUB1, promotes the interaction of STUB1 and STAT1, and consequently accelerate STUB1-mediated proteasomal degradation of STAT1 via K6-linked polyubiquitination at Lys240 and Lys652, thus weakens STAT1 triggered antiviral immune responses. More importantly, myeloid-specific deletion of Sec10 in mice showed enhanced IFN-I response against viral infection and improved survival of mice. Collectively, these findings demonstrate that Sec10 attenuates the JAK-STAT signaling pathway by targeting STAT1 for proteasomal degradation and identifies a previously unknown function of Sec10 in antiviral innate immunity and viral replication.

  PublisherOA PDFDOI

• Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB

  Nature Communications · 2025-01-08 · 10 citations

  articleOpen access

  Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone have been identified as tumor suppressors. However, their roles in virus infection remain unclear. Here, we demonstrate that PBLD upregulates the type I interferon (IFN-I) response through activating NF-kappaB (NF-κB) signaling pathway to resist viral infection in cells and mice. Mechanistically, PBLD activates NF-κB signaling pathway during viral infection via blocking tripartite motif containing 21 (TRIM21)-mediated phosphorylated inhibitory kappa B kinase beta (IKKβ) degradation. Furthermore, we show Cedrelone inhibits viral replication by increasing the PBLD protein expression and subsequently activating NF-κB-mediated IFN-I response. Furthermore, the therapeutic potential of Cedrelone lies in its ability to enhance antiviral immunity in primary macrophages and to promote survival and reduce lung tissue damage in HSV-1-infected mice in a PBLD-dependent manner. Consequently, our findings provide a potential combination model that targets PBLD for Cedrelone antiviral drug therapy, potentially paving the way for the development of broad-spectrum antiviral agents. Phenazine biosynthesis-like domain-containing protein (PBLD) and cedrelone play roles in tumor suppression. Here, authors suggest that PBLD and Cedrelone inhibit viral replication via activating the NF-κB-mediated IFN-I signaling response in cells and mice.

  PublisherOA PDFDOI

• Sec10 suppresses antiviral innate immune response by facilitating STUB1-mediated STAT1 degradation.

  UNC Libraries · 2025-10-09

  articleOpen access

  The exocyst complex is a heterooctameric protein complex, the individual components of the complex are thought to act on specific biological processes. However, the role of Sec10, the central subunit of the complex, in host defense and viral replication remains unclear. Here, we reported that Sec10 significantly impairs the activation of JAK-STAT signal pathway of type I IFN (IFN-I) response against both DNA- and RNA-viruses, and promotes viral replication, respectively. Mechanistically, Sec10 interacts with E3 ligase STUB1, promotes the interaction of STUB1 and STAT1, and consequently accelerate STUB1-mediated proteasomal degradation of STAT1 via K6-linked polyubiquitination at Lys240 and Lys652, thus weakens STAT1 triggered antiviral immune responses. More importantly, myeloid-specific deletion of Sec10 in mice showed enhanced IFN-I response against viral infection and improved survival of mice. Collectively, these findings demonstrate that Sec10 attenuates the JAK-STAT signaling pathway by targeting STAT1 for proteasomal degradation and identifies a previously unknown function of Sec10 in antiviral innate immunity and viral replication.

  PublisherDOI

• Exo70 promotes herpesvirus secretory vesicle tethering and virion release in an exocyst complex-dependent manner

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-03-08 · 1 citations

  preprintOpen access

  Abstract The exocyst complex, a multisubunit protein complex, mediates secretory vesicles fusion with the plasma membrane (PM) to deliver materials to the cell surface or to release cargoes to the extracellular space, but whether it is related to viral secretory vesicles tethering and virion release is unknown. Here, we identified that the exocyst complex subunit Exo70 promotes the trafficking of herpesvirus secretory vesicles and the release of mature virions in an exocyst complex-dependent manner. Mechanistically, mutation of Exo70 Lys632 and Lys635 diminishes viral secretory vesicles anchoring to PM. Moreover, the small GTPase Rab11a is necessary for the transport of viral secretory vesicles, and the Snapin-Exo70-SNAP23 axis is involved in fusion of viral secretory vesicles to the PM and release of virions. Most significantly, we discovered that Endosidin2 (ES2), an inhibitor of exocytosis via the exocyst complex, provides protection against herpesvirus infection in cells and mice. Overall, these findings unveil a previously uncharacterized role and mechanism of the exocyst complex in viral replication, highlighting its potential as an effective strategy against herpesvirus infection. Author summary Herpesviruses, such as herpes simplex virus 1 (HSV-1) and bovine herpes virus type 1 (BoHV-1), are highly prevalent pathogens that establish lifelong infections and cause various diseases in humans and animals. While the mechanisms underlying the transport of herpesvirus secretory vesicles from the Golgi to the PM and the subsequent viral release are still poorly understood. In our study, we have discovered that Exo70 promotes the trafficking of HSV-1 and BoHV-1 secretory vesicles and facilitates the release of mature virions in an exocyst complex-dependent manner. Mechanistically, both knockdown of Exo70 and a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-binding-deficient mutant of Exo70 caused virions to be trapped in the cytoplasm and unable to tether to PM, indicating that the binding of Exo70 to PI(4,5)P2 is critical for the docking virus secretory vesicles with PM. Additionally, the Snapin-Exo70-SNAP23 axis plays a pivotal role in the fusion between viral secretory vesicles and the PM, ultimately facilitating the release of virions. We found that Rab11a is necessary for viral secretory vesicle trafficking mediated by Exo70. Most importantly, we discovered that ES2, a transport inhibitor that combines with Exo70 to terminate the final stage of exocytosis via the exocyst complex, can protect cells and mice from α-herpesvirus infection.

  PublisherOA PDFDOI

• PBLD enhances antiviral innate immunity by promoting the p53–USP4–MAVS signaling axis

  Proceedings of the National Academy of Sciences · 2024-11-26 · 11 citations

  articleOpen access

  Phenazine biosynthesis-like domain-containing protein (PBLD) has been reported to be involved in the development of many cancers. However, whether PBLD regulates innate immune responses and viral replication is unclear. In this study, although it was found that the activity of PBLD extends to other PRRs, we focused on the RLR pathway activated via the p53-USP4-MAVS axis in response to virus infections. We found that PBLD deubiquitinates and stabilizes MAVS through ubiquitin-specific protease 4 (USP4) to promote antiviral innate immunity. Mechanistically, PBLD activates the transcription of USP4 via the upregulation of p53. USP4, which is a MAVS-interacting protein, substantially stabilizes the MAVS protein by deconjugating K48-linked ubiquitination chains from the MAVS protein at Lys461 during RNA virus infection. Most intriguingly, RNA virus-infected primary macrophages (peritoneal macrophages, PMs, and bone marrow-derived macrophages, BMDMs) and internal organ cells (lung and liver) from PBLD-deficient mice suppress the IFN-I response and promote viral replication. Notably, PBLD-deficient mice are more susceptible to RNA virus infection than their wild-type littermates. Our findings highlight a unique function of PBLD in antiviral innate immunity through the p53-USP4-MAVS signaling, providing a preliminary basis for research on PBLD as a target molecule for treating RNA virus infection.

  PublisherDOI

• PBLD promotes IRF3 mediated the type I interferon (IFN-I) response and apoptosis to inhibit viral replication

  Cell Death and Disease · 2024-10-03 · 12 citations

  articleOpen access

  Recent studies have implicated the phenazine biosynthesis-like domain-containing protein (PBLD) in the negative regulation of the development and progression of various cancers. However, its function in viral infection remains unknown. In this study, we found that PBLD plays important roles in multiple virus infections including BPIV3, SeV, VSV, and HSV-1. Our study revealed that PBLD enhances the expression of type I interferon (IFN-I) and ISGs through interferon regulatory factor 3 (IRF3). Further study indicated that PBLD promotes transcriptional phosphorylation of IRF3 (S385/386), thereby facilitating virus-induced IFN-I production. Interestingly, PBLD mediates virus-triggered mitochondrial apoptosis through its dependence on IRF3 (K313/315). Mechanistically, PBLD facilitated virus-induced apoptosis by recruiting the Puma protein to the mitochondria via IRF3. Additionally, we performed mutational analyses of IRF3, showing that its loss of either transcriptional or apoptotic function markedly increased viral replication. Moreover, macrophages with PBLD deficiency during viral infection exhibited decreased the IFN-I and ISGs expression, exacerbating viral infection. Importantly, mice deficient in PBLD exhibited increased viral replication and susceptibility to SeV infection, leading to decreased survival. Notably, Cedrelone, a chemical activator of PBLD, has the ability to reduce SeV replication. Collectively, we first discovered the new function of PBLD in viral infection, broadening our understanding of potential therapeutic targets and offering new insights for antiviral drug development.

  PublisherOA PDFDOI

Frequent coauthors

• Hongbin He

  Chinese Academy of Sciences

  10 shared

• Peili Hou

  Shandong Normal University

  8 shared

• Yuwei Gao

  Chinese Academy of Agricultural Sciences

  6 shared

• Wenqi He

  Henan Academy of Sciences

  4 shared

• Hongmei Wang

  Shandong Normal University

  4 shared

• Hongchao Zhu

  Shandong Normal University

  3 shared

• Fengyun Chu

  Shandong Normal University

  3 shared

• Cheng-Qiang He

  Shandong Normal University

  2 shared

Awards & honors

• Academic Fellowship, Center for Black, Brown, and Queer Stud…
• Andrew W. Mellon Postdoctoral Fellowship in the Humanities,…
• Charlotte W. Newcombe Dissertation Fellowship Honorable Ment…
• Mellon Foundation Dissertation Fellowship, 2016–17 (declined…
• Freeman Spogli Institute China Fund Dissertation Fellowship,…