Qin Li

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Assistant Professor of Genetics
Department: Genetics

Contact information
Department of Genetics
540 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104
BS (Biological Science)
Peking University, 2009.
PhD (Biochemistry and Molecular Biology)
Peking University, 2014.
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Description of Research Expertise

A hallmark of our immune system is the ability to discriminate between self and non-self molecules. To achieve this goal, cells utilize various sensors to recognize patterns frequently found in pathogens. Yet how cells avoid unwanted recognition of self molecules to prevent autoimmunity is poorly understood.

MDA5 is a cytosolic receptor that recognizes viral double-stranded RNAs (dsRNAs) to activate the antiviral IFN response. How does MDA5 avoid sensing self dsRNAs? The answer is Adenosine-to-Inosine (A-to-I) RNA editing catalyzed by ADAR that labels endogenous dsRNAs as self to evade MDA5 sensing. Mice deficient with ADAR1 editing are embryonic lethal, but can be rescued to full life span when MDA5 is removed. In humans, ADAR1 loss-of-function and MDA5 gain-of-function mutations lead to rare autoimmune diseases such as Aicardi-Gouteries Syndrome. While aberrant activation of MDA5 sensing is deleterious in healthy individuals, it can be beneficial in cancer immunotherapy. RNA editing occurs at millions of sites across human tissues (Tan, Li et al., Nature 2017), but it was unclear which dsRNAs, if not properly edited, are immunogenic, and what role the ADAR1-dsRNA-MDA5 axis plays in common diseases.

During his postdoctoral training, Dr. Li discovered that RNA editing quantitative trait loci (edQTLs) are strongly enriched in GWAS signals of inflammatory diseases, even more than gene expression and RNA splicing QTLs. Furthermore, he showed that GWAS risk alleles, by each reducing editing level of their nearby immunogenic dsRNAs, can collectively elicit MDA5-dependent dsRNA sensing and subsequent chronic inflammation in a wide range of autoimmune and inflammatory diseases (Li et al., Nature 2022). These findings, based on well-established mechanism and human genetic evidence, show that insufficient RNA editing is a major risk factor underlying inflammatory diseases.

The Li lab’s research combines computational and experimental approaches to understand basic mechanisms by which our immune systems distinguish self and non-self RNAs. We are also interested in understanding the contribution of cellular RNA burden to inflammation and autoimmune disease.

Selected Publications

Qin Li, Mike Gloudemans, Francois Aguet, Gokul Ramaswami, Tao Sun, Yang I. Li, The GTEx Consortium, Jonathan Pritchard, Stephen Montgomery, Jin Billy Li: RNA editing underlies genetic risk of common inflammatory diseases. RNA Editing, Gordon Research Conference, Ventura, CA, March 19-24, 2023 Mar 2023 Notes: Poster.

Li Q, Gloudemans MJ, Geisinger JM, Fan B, Aguet F, Sun T, Ramaswami G, Li YI, Ma JB, Pritchard JK, Montgomery SB, Li JB: RNA editing underlies genetic risk of common inflammatory diseases. Nature 608(7923): 569-577, Aug 2022.

T Sun*, Q Li*, JM Geisinger, SB Hu, B Fan, S Su, WT Tsui, HC Guo, JB Ma, JB Li: A Small Subset of Cytosolic dsRNAs Must Be Edited by ADAR1 to Evade MDA5-Mediated Autoimmunity. bioRXiv 2022 Notes: Preprint.

X Liu, T Sun, A Shcherbina, Q Li, I Jarmoskaite, K Kappel, G Ramaswami, R Das, A Kundaje, JB Li: Learning cis-regulatory principles of ADAR-based RNA editing from CRISPR-mediated mutagenesis. Nature Communications 12(1): 1-17, Apr 2021.

Liu X, Sun T, Shcherbina A, Li Q, Jarmoskaite I, Kappel K, Ramaswami G, Das R, Kundaje A, Li JB: Learning cis-regulatory principles of ADAR-based RNA editing from CRISPR-mediated mutagenesis. Nat Commun 12(1): 2165, Apr 2021.

The GTEx Consortium: GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369(6509): 1318-1330, Sep 2020.

Sapiro AL, Freund EC, Restrepo L, Qiao HH, Bhate A, Li Q, Ni JQ, Mosca TJ, Li JB: Zinc Finger RNA-Binding Protein Zn72D Regulates ADAR-Mediated RNA Editing in Neurons. Cell Rep 31(7): 107654, May 2020.

Freund EC, Sapiro AL, Li Q, Linder S, Moresco JJ, Yates JR 3rd, Li JB: Unbiased Identification of trans Regulators of ADAR and A-to-I RNA Editing. Cell Rep 31(7): 107656, May 2020.

Breen MS, Dobbyn A, Li Q, Roussos P, Hoffman GE, Stahl E, Chess A, Sklar P, Li JB, Devlin B, Buxbaum JD, CommonMind Consortium: Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia. Nat Neurosci 22(9): 1402-1412, Sep 2019.

Merkle T, Merz S, Reautschnig P, Blaha A, Li Q, Vogel P, Wettengel J, Li JB, Stafforst T: Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides. Nat Biotechnol 37(2): 133-138, Feb 2019.

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Last updated: 04/29/2024
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