Hachung Chung, Ph.D.
Assistant Professor of Microbiology & Immunology
Ph.D., Harvard University
Understanding how self-RNA sensing shapes human immune responses
Decades of research in innate immunity has unraveled how the host uses pattern recognition receptors (PRRs) to detect microbial DNA and RNA to mount an immune response that counteracts infection. However, these findings raise an intriguing question: How does the host suppress immune responses to their own DNA or RNA? This is a fundamental question in biology and a topic of high clinical relevance as we start to recognize how self-nucleic acid sensing by our immune system can cause autoimmune diseases, and also be used for immunomodulatory therapies for diseases such as cancer.
How our immune system suppresses immune responses to our own RNA (self-RNA) still remains mostly a mystery. Using human cell culture models, we have demonstrated that ADAR1 (Adenosine Deaminase Acting on RNA) - an RNA editing enzyme responsible for Adenosine (A) - to - Inosine (I) editing of double stranded RNA - plays a major role in preventing self-RNAs from activating PRRs. We are just at the tip of the iceberg in understanding how ADAR1 suppresses autoinflammation. There are two main areas of research in our lab:
1) First, we would like to elucidate the mechanism by which ADAR1 suppresses self-RNAs from triggering autoinflammation and further understand how these mechanisms are regulated in different cell types (e.g. neural cells).
2) Second, we would like to investigate how self-RNA sensing shapes human immune responses during health and disease.
The Chung lab is always looking for curious, passionate, and positive researchers (postdocs, clinical scholars, graduate students, medical students, undergraduates, and technicians) to join our team. To inquire about positions please email Dr. Chung with a cover letter and CV.
Chung H. and Rice C.M. (2018) T time for ADAR: ADAR1 is required for T cell self-tolerance. EMBO Rep. 19: e47237.
Chung H., Calis J.J.A., Wu X., Sun T., Yu Y., Sarbanes S.L., Dao Thi V.L., Shilvock A.R., Hoffmann H.H., Rosenberg B.R. and Rice C.M. (2018) Human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell 172: 811-824 e14.
Yu Y., Scheel T.K.H., Luna J.M., Chung H., Nishiuchi E., Scull M.A., Echeverria N., Ricardo-Lax I., Kapoor A., Lipkin W.I., Divers T.J., Antczak D.F., Tennant B.C. and Rice C.M. (2017) miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence. PLoS Pathology 13: e1006694.
Chung H., Pamp S.J., Hill J.A., Surana N.K., Edelman S.M., Troy E.B., Reading N.C., Villablanca E.J., Wang S., Mora J.R., Umesaki Y., Mathis D., Benoist C., Relman D.A. and Kasper D.L. (2012) Gut immune maturation depends on colonization with a host-specific microbiota. Cell 149:1578-1593.
Chung H. and Kasper D.L. (2010) Microbiota-stimulated immune mechanisms to maintain gut homeostasis. Curr. Opin. Immunol. 22: 455-460.
Duan J., Chung H., Troy E. and Kasper D.L. (2010) Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma/delta T cells. Cell Host Microbe 7:140-150.
Gryllos I., Tran-Winkler H.J., Cheng M.F., Chung H., Bolcome R., 3rd, Lu W., Lehrer R.I. and Wessels M.R. (2008) Induction of group A Streptococcus virulence by a human antimicrobial peptide. Proc. Natl. Acad. Sci. U.S.A. 105: 16755-16760.
Ryndak M.B., Chung H., London E. and Bliska J.B. (2005) Role of predicted transmembrane domains for type III translocation, pore formation, and signaling by the Yersinia pseudotuberculosis YopB protein. Infect. Immun. 73: 2433-2443.