Mellon College of Science › Biological Sciences › People › Faculty › Zheng Kuang

Zheng Kuang

Assistant Professor

Address:
651 Mellon Institute
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213

Education

M.S., Computer Science, Georgia Institute of Technology
M.H.S., Biostatistics, Johns Hopkins University
Ph.D., Molecular Biology, Johns Hopkins University
Postdoctoral Fellow, Department of Immunology, University of Texas Southwestern Medical Center

Research

Trillions of different microorganisms reside in our gut, known as the gut microbiota. The microbiota has emerged as a very important environmental factor regulating a wide range of host physiological processes, including metabolism, immune functions and circadian rhythms. The goal of our research is to identify the molecular basis of interactions between the microbiota and the circadian rhythms in mammalian metabolism and immunity. We use various techniques including genomics, gnotobiotics, laser capture microscopy to delve deeper into the transcriptional and epigenetic mechanisms that regulate host-microbial interactions. We anticipate that these efforts will lead to important new insight into how intestinal microbes regulate host physiological functions, and identify new avenues for developing therapeutics against metabolic and immunological diseases of the intestine.

Microbial regulation of circadian rhythms in the intestine

Identify regulatory factors that interact with intestinal HDAC3.
HDAC3 is a histone deacetylase that removes acetylation on histones and represses transcription. It also deacetylates non-histone proteins and regulates their functions. We have identified HDAC3 as a key molecule integrating microbial and circadian cues in the gut. In ongoing work, we are investigating how gut bacteria regulate HDAC3 and how HDAC3 controls various circadian programs to impact metabolic health and immune responses.
Determine epigenetic mechanisms underlying the cross-talk between the microbiota and circadian pathways.
Mammalian metabolic immune activities and immune responses are temporal orchestrated in accordance with diurnal sleep-wake and feeding-fasting cycles. It is becoming clear that the gut microbiota impacts these circadian rhythms, yet the underlying mechanisms are largely unknown. We have demonstrated that the gut microbiota is essential for the rhythms of histone acetylation, which suggested that epigenetic regulation is a key mechanism by which the microbiota impacts host circadian pathways. In ongoing work, we are identifying epigenetic modifications that have microbiota-dependent rhythms and studying their functions.

Microbiota-dependent epigenetic regulation of mucosal barrier functions

A harmonious mutualistic environment is critical for both the intestinal epithelium and bacteria to perform their metabolic reactions. However, excessive or abnormal host-microbial interactions pose a threat to metabolic health instead. Intestinal epithelial cells limit bacterial attachment and invasion by (1) forming a physical barrier with tight junctions; (2) secreting mucins which form the mucus layer that physically separates bacteria from host; and (3) secreting anti-microbial proteins that kill bacteria or restrict their growth. Mucins and antimicrobial proteins are synthesized and secreted mainly by two lineages of specialized epithelial cells: Paneth cells and Goblet cells. Despite the importance of these secretory cells in mucosal defense, how their activities are regulated remains largely unknown. In ongoing work, we are exploring epigenetic mechanisms by which the microbiota regulates these secretory cells to impact mucosal barrier functions.

Publications

Kuang Z, Wang Y, Li Y, Ye C, Ruhn KA, Behrendt CL, Olson EN, Hooper LV. The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science. 2019 Sep 27;365(6460):1428-1434. doi: 10.1126/science.aaw3134. PubMed PMID: 31604271; PubMed Central PMCID: PMC7158748.

De Ioannes P, Leon VA, Kuang Z, Wang M, Boeke JD, Hochwagen A, Armache KJ. Structure and function of the Orc1 BAH-nucleosome complex. Nat Commun. 2019 Jul 1;10(1):2894. doi: 10.1038/s41467-019-10609-y. PubMed PMID: 31263106; PubMed Central PMCID: PMC6602975.

Harris TA, Gattu S, Propheter DC, Kuang Z, Bel S, Ruhn KA, Chara AL, Edwards M, Zhang C, Jo JH, Raj P, Zouboulis CC, Kong HH, Segre JA, Hooper LV. Resistin-like Molecule α Provides Vitamin-A-Dependent Antimicrobial Protection in the Skin. Cell Host Microbe. 2019 Jun 12;25(6):777-788.e8. doi: 10.1016/j.chom.2019.04.004. Epub 2019 May 14. PubMed PMID: 31101494; PubMed Central PMCID: PMC6628910.

Gattu S, Bang YJ, Pendse M, Dende C, Chara AL, Harris TA, Wang Y, Ruhn KA, Kuang Z, Sockanathan S, Hooper LV. Epithelial retinoic acid receptor β regulates serum amyloid A expression and vitamin A-dependent intestinal immunity. Proc Natl Acad Sci U S A. 2019 May 28;116(22):10911-10916. doi: 10.1073/pnas.1812069116. Epub 2019 May 16. PubMed PMID: 31097581; PubMed Central PMCID: PMC6561173.

Ye C, Sutter BM, Wang Y, Kuang Z, Zhao X, Yu Y, Tu BP. Demethylation of the Protein Phosphatase PP2A Promotes Demethylation of Histones to Enable Their Function as a Methyl Group Sink. Mol Cell. 2019 Mar 21;73(6):1115-1126.e6. doi: 10.1016/j.molcel.2019.01.012. Epub 2019 Feb 13. PubMed PMID: 30772176; PubMed Central PMCID: PMC6628921.

Sánchez-Gaya V, Casaní-Galdón S, Ugidos M, Kuang Z, Mellor J, Conesa A, Tarazona S. Elucidating the Role of Chromatin State and Transcription Factors on the Regulation of the Yeast Metabolic Cycle: A Multi-Omic Integrative Approach. Front Genet. 2018;9:578. doi: 10.3389/fgene.2018.00578. eCollection 2018. PubMed PMID: 30555512; PubMed Central PMCID: PMC6284056.

Kuang Z, Ji H, Boeke JD. Stress response factors drive regrowth of quiescent cells. Curr Genet. 2018 Aug;64(4):807-810. doi: 10.1007/s00294-018-0813-0. Epub 2018 Feb 17. Review. PubMed PMID: 29455333; NIHMSID:NIHMS944262.

Venkataraman A, Yang K, Irizarry J, Mackiewicz M, Mita P, Kuang Z, Xue L, Ghosh D, Liu S, Ramos P, Hu S, Bayron Kain D, Keegan S, Saul R, Colantonio S, Zhang H, Behn FP, Song G, Albino E, Asencio L, Ramos L, Lugo L, Morell G, Rivera J, Ruiz K, Almodovar R, Nazario L, Murphy K, Vargas I, Rivera-Pacheco ZA, Rosa C, Vargas M, McDade J, Clark BS, Yoo S, Khambadkone SG, de Melo J, Stevanovic M, Jiang L, Li Y, Yap WY, Jones B, Tandon A, Campbell E, Montelione GT, Anderson S, Myers RM, Boeke JD, Fenyö D, Whiteley G, Bader JS, Pino I, Eichinger DJ, Zhu H, Blackshaw S. A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors. Nat Methods. 2018 May;15(5):330-338. doi: 10.1038/nmeth.4632. Epub 2018 Mar 19. PubMed PMID: 29638227; PubMed Central PMCID: PMC6063793.

Kuang Z, Ji Z, Boeke JD, Ji H. Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes. Nucleic Acids Res. 2018 Jan 9;46(1):e2. doi: 10.1093/nar/gkx905. PubMed PMID: 29325176; PubMed Central PMCID: PMC5758894.

Kuang Z, Canzar S. Tracking Alternatively Spliced Isoforms from Long Reads by SpliceHunter. Methods Mol Biol. 2018;1751:73-88. doi: 10.1007/978-1-4939-7710-9_5. PubMed PMID: 29508290.

Kuang Z, Pinglay S, Ji H, Boeke JD. Msn2/4 regulate expression of glycolytic enzymes and control transition from quiescence to growth. Elife. 2017 Sep 26;6. doi: 10.7554/eLife.29938. PubMed PMID: 28949295; PubMed Central PMCID: PMC5634782.

Wang Y, Kuang Z, Yu X, Ruhn KA, Kubo M, Hooper LV. The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science. 2017 Sep 1;357(6354):912-916. doi: 10.1126/science.aan0677. PubMed PMID: 28860383; PubMed Central PMCID: PMC5702268.

Ye C, Sutter BM, Wang Y, Kuang Z, Tu BP. A Metabolic Function for Phospholipid and Histone Methylation. Mol Cell. 2017 Apr 20;66(2):180-193.e8. doi: 10.1016/j.molcel.2017.02.026. Epub 2017 Mar 30. PubMed PMID: 28366644; PubMed Central PMCID: PMC5482412.

Zhang W, Zhao G, Luo Z, Lin Y, Wang L, Guo Y, Wang A, Jiang S, Jiang Q, Gong J, Wang Y, Hou S, Huang J, Li T, Qin Y, Dong J, Qin Q, Zhang J, Zou X, He X, Zhao L, Xiao Y, Xu M, Cheng E, Huang N, Zhou T, Shen Y, Walker R, Luo Y, Kuang Z, Mitchell LA, Yang K, Richardson SM, Wu Y, Li BZ, Yuan YJ, Yang H, Lin J, Chen GQ, Wu Q, Bader JS, Cai Y, Boeke JD, Dai J. Engineering the ribosomal DNA in a megabase synthetic chromosome. Science. 2017 Mar 10;355(6329). doi: 10.1126/science.aaf3981. PubMed PMID: 28280149.

Mitchell LA, Wang A, Stracquadanio G, Kuang Z, Wang X, Yang K, Richardson S, Martin JA, Zhao Y, Walker R, Luo Y, Dai H, Dong K, Tang Z, Yang Y, Cai Y, Heguy A, Ueberheide B, Fenyö D, Dai J, Bader JS, Boeke JD. Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond. Science. 2017 Mar 10;355(6329). doi: 10.1126/science.aaf4831. PubMed PMID: 28280154.

Wu Y, Li BZ, Zhao M, Mitchell LA, Xie ZX, Lin QH, Wang X, Xiao WH, Wang Y, Zhou X, Liu H, Li X, Ding MZ, Liu D, Zhang L, Liu BL, Wu XL, Li FF, Dong XT, Jia B, Zhang WZ, Jiang GZ, Liu Y, Bai X, Song TQ, Chen Y, Zhou SJ, Zhu RY, Gao F, Kuang Z, Wang X, Shen M, Yang K, Stracquadanio G, Richardson SM, Lin Y, Wang L, Walker R, Luo Y, Ma PS, Yang H, Cai Y, Dai J, Bader JS, Boeke JD, Yuan YJ. Bug mapping and fitness testing of chemically synthesized chromosome X. Science. 2017 Mar 10;355(6329). doi: 10.1126/science.aaf4706. PubMed PMID: 28280152; PubMed Central PMCID: PMC5679077.

Xie ZX, Li BZ, Mitchell LA, Wu Y, Qi X, Jin Z, Jia B, Wang X, Zeng BX, Liu HM, Wu XL, Feng Q, Zhang WZ, Liu W, Ding MZ, Li X, Zhao GR, Qiao JJ, Cheng JS, Zhao M, Kuang Z, Wang X, Martin JA, Stracquadanio G, Yang K, Bai X, Zhao J, Hu ML, Lin QH, Zhang WQ, Shen MH, Chen S, Su W, Wang EX, Guo R, Zhai F, Guo XJ, Du HX, Zhu JQ, Song TQ, Dai JJ, Li FF, Jiang GZ, Han SL, Liu SY, Yu ZC, Yang XN, Chen K, Hu C, Li DS, Jia N, Liu Y, Wang LT, Wang S, Wei XT, Fu MQ, Qu LM, Xin SY, Liu T, Tian KR, Li XN, Zhang JH, Song LX, Liu JG, Lv JF, Xu H, Tao R, Wang Y, Zhang TT, Deng YX, Wang YR, Li T, Ye GX, Xu XR, Xia ZB, Zhang W, Yang SL, Liu YL, Ding WQ, Liu ZN, Zhu JQ, Liu NZ, Walker R, Luo Y, Wang Y, Shen Y, Yang H, Cai Y, Ma PS, Zhang CT, Bader JS, Boeke JD, Yuan YJ. “Perfect” designer chromosome V and behavior of a ring derivative. Science. 2017 Mar 10;355(6329). doi: 10.1126/science.aaf4704. PubMed PMID: 28280151.

Kuang Z, Boeke JD, Canzar S. The dynamic landscape of fission yeast meiosis alternative-splice isoforms. Genome Res. 2017 Jan;27(1):145-156. doi: 10.1101/gr.208041.116. Epub 2016 Nov 17. PubMed PMID: 27856494; PubMed Central PMCID: PMC5204338.