The precise regulation of endogenous double-stranded RNAs (dsRNAs) is essential to prevent them from being misrecognized as viral RNAs by the innate immune system, which could trigger an immune response. Dysregulation of dsRNAs can lead to autoimmune diseases and non-infectious inflammation. However, it can also be harnessed for cancer immunotherapy. Our lab focuses on the fundamental question of how cells avoid immune responses triggered by endogenous dsRNAs. We investigate the regulation of dsRNA and immune responses in both health and disease.

Our research directions include:

1. Developing new methods to identify endogenous dsRNAs and its binding proteins.

2. Systematically identifying regulatory networks involved in dsRNA-mediated innate immune responses.

3. Exploring the role of dsRNA in autoimmune diseases and cancer therapy.

Dr. Hu has been dedicated to studying the mechanisms of nucleic acid immunity, with a focus on the regulation of endogenous double-stranded RNA (dsRNA). His research has uncovered multiple regulatory pathways of endogenous dsRNA and revealed the immune tolerance mechanisms that prevent self-dsRNA from triggering autoimmune responses. His key research contributions include:

1. Discover mechanisms by which cells avoid innate immune responses to self-dsRNA: Dr. Hu demonstrated that the RNA-editing enzyme ADAR1 suppresses the activation of dsRNA immune receptors MDA5 and PKR through two distinct molecular mechanisms. ADAR1 edits endogenous dsRNA to prevent its recognition by MDA5 and competitively binds to dsRNA to inhibit PKR activation (Hu et al., Molecular Cell, 2023). This study provided significant insights into how cells prevent immune responses to self-dsRNA, offering a theoretical basis for understanding autoimmune diseases and developing tumor immunotherapies.

2. Uncover the regulatory mechanism and function of dsRNA nuclear retention mediated by paraspeckles: Dr. Hu's research showed that endogenous dsRNA is retained in the nucleus by paraspeckles, a type of nuclear bodies, and that this retention is regulated by stimuli and mitochondrial stress (Hu et al., Genes and Development, 2015; Wang, Hu et al., Nature Cell Biology, 2018). These findings expanded the understanding of gene expression regulation by systematically elucidating the nuclear retention mechanism of dsRNA, providing a foundation for further investigation into the regulation and function of endogenous dsRNA.

3. Inventa vector for expressing nucleic acid in the nucleus: Dr. Hu contributed to the development of a novel vector that enables nucleic acids to be expressed and enriched in the nucleus (Yin, Hu et al., Nucleic Acids Research, 2015). This tool has become a valuable resource for studying the functions of nuclear long non-coding RNAs (lncRNAs).

2020-2023  Tobacco-Related Disease Research Program Postdoctoral Fellowship

2018-2019  The Stanford Dean’s Postdoctoral Fellowship

2017  Outstanding Graduate of Shanghai Higher Education Institutions

2015  National Scholarship for Outstanding Graduate Student

2015  Pacemaker to Merit Student, Chinese Academy of Sciences

2015  CAS President Award, Chinese Academy of Sciences

First-Author Publications

1. Hu SB, and Li JB. RNA editing and immune control: from mechanism to therapy. Curr Opin Genet Dev 2024, 86: 102195.

https://www.sciencedirect.com/science/article/pii/S0959437X24000443

2. Hu SB*, Heraud-Farlow J*, Sun T, Liang Z, Goradia A, Taylor S, Walkley CR, Li JB. ADAR1p150 prevents MDA5 and PKR activation via distinct mechanisms to avert fatal autoinflammation. Mol Cell2023, 83: 3869-3884.

https://www.cell.com/molecular-cell/fulltext/S1097-2765(23)00740-2

• Previews by Dorrity TJ and Chung H, Mol Cell, 2023, 83(21): 3760-3762

3. Wang Y*, Hu SB*(co-first author), Wang MR, Yao RW, Wu D, Yang L, Chen LL. Genome-wide screening of NEAT1 regulators reveals cross-regulation between paraspeckles and mitochondria. Nat Cell Biol2018, 20:1145–1158.

https://www.nature.com/articles/s41556-018-0204-2

• News and Views by Fox AH, Nat Cell Biol, 2018, 20(10): 1108-1109

4. Hu SB, Yao RW, Chen LL. Shedding light on paraspeckle structure by super-resolution microscopy. J Cell Biol 2016, 214(7):789-91.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037413/

5. Hu SB, Xiang JF, Li X, Xu YF, Xue W, Huang M, Wong CC, Sagum CA, Bedford MT, Yang L, Cheng D and Chen LL. Protein arginine methyltransferase CARM1 attenuates the nuclear retention of mRNAs containing IRAlus at paraspeckles. Genes & Dev 2015, 29: 630-645. https://genesdev.cshlp.org/content/29/6/630.long

• Perspectives by Elbarbary RA and Maquat LE, Genes & Dev, 2015, 29:687-689

• Research highlights by Bull Chin Acad Sci, 2015, 29:108

6. Yin QF*, Hu SB*(co-first author), Xu YF, Yang L, Carmichael GG, Chen LL. SnoVectors for nuclear expression of RNA. Nucleic Acids Res 2015, 43:e5.

https://academic.oup.com/nar/article/43/1/e5/2902592

Collaborative Publications

7. Heraud-Farlow JE, Taylor SR, Chalk AM, Escudero A, Hu SB, Goradia A, Sun T, Li Q, Nikolic I, Li JB, Fidalgo M, Guallar D, Simpson KJ, Walkley CR. GGNBP2 regulates MDA5 sensing triggered by self double-stranded RNA following loss of ADAR1 editing. Sci Immunol. 2024;9(101):eadk0412.

https://www.science.org/doi/full/10.1126/sciimmunol.adk0412

8. Sun T, Qin L, Geisinger J, Hu SB, Fan B, Su SC, Tsui WT, Guo HC, Ma JB, Li JB. A small subset of cytosolic dsRNAs must be edited by ADAR1 to evade MDA5-mediated autoimmunity. bioRxiv 2022.

https://www.biorxiv.org/content/10.1101/2022.08.29.505707v1.full

9. Xing YH, Bai Z, Liu CX, Hu SB, Ruan M, Chen LL. Research progress of long noncoding RNA in China. IUBMB Life 2016.

https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1002/iub.1564

https://smart.org.cn/recruitment/research-team/position/post_1241583.html