CRISPR/Cas technology development

Gene editing technology development

Epigenome editing technology development

RNA editing technology development

Synthetic Biology

Gene Therapy

RNA Therapy

Epigenome

3D Genome

Alternative Splicing

Bioinformatics

2023-12~Present, Institute of Zoology, Chinese Academy of Sciences, Principle Investigator

2023-12~Present, University of Chinese Academy of Sciences, Professor

2022-01~2023-11, Arizona State University, Associate Professor (PhD supervisor)

2015-07~2021-12, Jackson Laboratory, Assistant Professor (PhD supervisor)

2014-06~2015-07, Jackson Laboratory, JAX Scholar Postdoc

(*equal contribution, #corresponding)

1.     Wu, M.*, Hau, P.-M.*, Li, L.*, Tsang, C.M., Yang, Y., Taghbalout, A., Chung, G.T.Y., Hui, S.Y., Tang, W.C., Jillette, N., Zhu, J.J., Lee, H.H.Y., Kong, E.L., Chan, M.S.A., Chan, J.Y.K., Ma, B.B.Y., Chen, M.-R., Lee, C., To, K.F., Cheng, A.W.#, Lo, K.-W.# (2024) Synthetic BZLF1-targeted transcriptional activator for efficient lytic induction therapy against EBV-associated epithelial cancers. Nature Communications 15:3729 doi: 10.1038/s41467-024-48031-8 (co-corresponding) IF=17.694

2.     Rana, V., Peng, J., Pan, C., Lyu, H., Cheng, A., Kim, M., Milenkovic, O. (2024) Interpretable Online Network Dictionary Learning for Inferring Long-Range Chromatin Interactions. PLOS Computational Biology 20(5): e1012095. doi: 10.1371/journal.pcbi.1012095

3.     Kim, M.*, Wang, P.*, Clow, P.*, Chien, I., Wang, X., Peng, J., Chai, H., Liu, X., Lee, B., Ngan, C.Y., Yue, F., Milenkovic, O., Chuang, J., Wei, C.-L., Casellas, R., Cheng, A.W.#, Ruan, Y.# (2024) Multifaceted roles of cohesin in regulating transcriptional loops. BioRxiv (preprint) doi: 10.1101/2024.03.25.586715

4.     Liou, R.H.-C., Urrutia-Cabrera, D., Westin, I. M., Golovleva, I., Liu, G.-S., Kumar, S., McLenachan, S., Chen, F.K., Hsu, F.-T., Edwards, T., Martin, K.R., Cheng, A.W., Wong, R.C.B (2024) Using RNA-targeting CRISPR-Cas13 and engineered U1 systems to reduce ABCA4 splice variants in Stargardt disease. BioRxiv (preprint) doi: 10.1101/2024.03.08.584155

5.     Liu, Z., Jillette N., Robson, P., Cheng, A.W.# (2023) Simultaneous multifunctional transcriptome engineering by CRISPR RNA scaffold. Nucleic Acid Research gkad547 doi: 10.1093/nar/gkad547. IF=19.16

6.     Lasry R., Maoz, N., Cheng, A.W., Tov, N.Y., Kulenkampff, E., Azagury, M., Yang, H., Ople, C., Markoulaki, S., Faddah D.A., Makedonski, K., Orzech, D., Sabag, O., Jaenisch, R., Buganim, Y.# (2023) Complex Haploinsufficiency in Pluripotent Cells Yields Somatic Cells with DNA Methylation Abnormalities and Pluripotency Induction Defects. Stem Cell Reports 18:1-16. IF=5.9

7.     Clow, P.A., Du, M., Jillette, N., Taghbalout, A., Zhu, J.J.#, Cheng, A.W.# (2022) CRISPR-mediated multiplexed live cell imaging of nonrepetitive genomic loci with one guide RNA per locus. Nature Communications 13:1871. doi: 10.1038/s41467-022-29343-z. IF=17.694

8.     Yi, E., Gujar, A.D., Guthrie, M., Kim, H., Zhao, D., Johnson K.C., Amin, S.B., Costa, M.L., Yu, Q., Das, S., Jillette, N., Clow, P.A., Cheng, A.W.#, Verhaak, R.G.W.# (2022) Live-cell imaging shows uneven segregation of extrachromosomal DNA elements and transcriptionally active extrachromosomal DNA hubs in cancer. Cancer Discovery doi: 10.1158/2159-8290.CD-21-1376 (co-corresponding) IF=39.397

9.     Zhu, J.J., Cheng, A.W.# (2022) JACKIE: Fast enumeration of genome-wide single- and multi-copy CRISPR target sites and their off-target numbers. The CRISPR Journal doi: 10.1089/crispr.2022.0042 IF=4.321

10.  Jillette, N., Zhu, J.J.#, Cheng, A.W.# (2022) Local recruitment of DNA repair proteins enhances CRISPR-ssODN-HDR editing. BioRxiv (preprint). doi: https://doi.org/10.1101/2022.04.13.488255

11.  Jillette, N., Zhu, J.J.#, Cheng, A.W.# (2022) Targeted directional kilobase sequence insertion by combining prime editing with recombinases or integrases. BioRxiv (preprint). doi: https://doi.org/10.1101/2022.05.25.493515

12.  Taghbalout, A., Jillette, N., Cheng, A.W.# (2021) TALE.Sense: A Versatile DNA Sensor Platform for Live Mammalian Cells. ACS Synthetic Biology doi: 10.1021/acssynbio.1c00212 IF=5.249

13.  Du, M.*, Jillette, N.*, Zhu, J.J., Li, S., Cheng, A.W.# (2020) CRISPR Artificial Splicing Factors. Nature Communications 11:2973. doi: 10.1038/s41467-020-16806-4 IF=17.694

14.  Zhu, J.J., Jillette, N., Li X., Cheng, A.W.#, Lau C.C.# (2020) C11orf95-RELA Reprograms 3D Epigenome in Supratentorial Ependymoma. Acta Neuropathologica doi: 10.1007/s00401-020-02225-8 (co-corresponding) IF=21.534

15.  Ashoor, H., Chen, X., Rosikiewicz, W., Wang, J., Cheng, A.W., Wang, P., Ruan, Y., Li, S.# (2020) Graph embedding and unsupervised learning predict genomic sub-compartments from HiC chromatin interaction data. Nature Communications 11:1173. doi: 10.1038/s41467-020-14974-x IF=17.694

16.  Leclair, N., Brugiolo, M., Urbanski, L., Lawson, S.C., Thakar, K., Yurieva, M., George J., Hinson, J.T., Cheng, A., Graveley, B.R., Anczukow, O.# (2020) Poison exon splicing regulates a coordinated network of SR protein expression during differentiation and tumorigenesis. Molecular Cell 80(4):468-665.e9 doi: 10.1016/j.molcel.2020.10.019. IF=19.33

17.  Taghbalout, A., Du, M., Jillette, N., Rosikiewicz, W. Rath, A., Heinen, C., Li, S., Cheng, A.W.# (2019) Enhanced CRISPR-based DNA demethylation by Casilio-ME-mediated RNA-guided coupling of methylcytosine oxidation and DNA repair pathways. Nature Communications 10:4296. doi:10.1038/s41467-019-12339-7 IF=17.694

18.  Jillette, N.*., Du, M.*, Zhu, J.J., Cardoz, P., Cheng, A.W.# (2019) Split Selectable Markers. Nature Communications 10:4968. doi: 10.1038/s41467-019-12891-2 IF=17.694

19.  Cheng, A.W.*#, Jillette, N.*, Lee, P., Plaskon, D., Fujiwara, Y., Wang, W., Taghbalout, A., Wang, H.# (2016) Casilio: a versatile CRISPR-Cas9-Pumilio hybrid for gene regulation and genomic labeling. Cell Research 26:254–257. doi: 10.1038/cr.2016.3 PMID:26768771 (co-corresponding) IF=46.3

20.  Liu X., Zhang Y., Cheng C., Cheng, A.W., Zhang, X., Li N., Xia, C., Wei, X., Liu X., Wang, H.# (2016) CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells. Cell Research 27:154-157. doi:10.1038/cr.2016.142 PMID: 27910851 IF=46.3

21.  Wiles, M.V., Qin, W., Cheng, A.W., Wang, H.# (2015) CRISPR-Cas9-mediated genome editing and guide RNA design. Mammlian Genome DOI 10.1007/s00335-015-9565-z IF=2.078

22.  Qin, W., Dion, S.L., Kutny, P.M., Zhang, Y., Cheng, A.W., Jillette, N.L., Malhotra, A., Geurts, A.M., Chen, Y.-G., Wang, H.# (2015) Efficient CRISPR/Cas9-mediated genome editing in mice by zygote electroporation of nuclease. Genetics 115.176594 IF=4.402

23.  Cheng, A.W.*, Shi, J.*, Wong, P.*, Luo, K.L., Trepman, P., Wang, E.T., Choi, H., Burge, C.B., Lodish, H.F.# (2014) Muscleblind-like 1 (Mbnl1) regulates pre-mRNA alternative splicing during terminal erythropoiesis. Blood doi: 10.1182/blood-2013-12-542209 PMID: 24869935 IF=25.48

24.  Han, Y., Slivano, O.J., Christie, C.K., Cheng, A.W., Miano, J.M.# (2014) CRISPR-Cas9 Genome Editing of a Single Regulatory Element Nearly Abolishes Target Gene Expression in Mice. Arterioscler Thromb Vasc Biol. pii: ATVBAHA.114.305017. PMID: 25538209 IF=10.51

25.  Katz, Y., Li, F., Lambert, N.J., Sokol, E.S., Tam, W.L., Cheng, A.W., Airoldi, E.M., Lengner, C.J., Gupta, P.B., Yu, Z., Jaenisch, R., Burge, C.B.# (2014) Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state. Elife doi: 10.7554/eLife.03915. PMID: 25380226

26.  Wu, X., Scott, D.A., Kriz, A.J., Chiu, A.C., Hsu, P.D., Dadon, D.B., Cheng, A.W., Trevino, A.E., Konermann, S., Chen, S., Jaenisch, R., Zhang, F., Sharp, P.A.# (2014) Genome-wide binding of CRISPR endonuclease Cas9 in mammalian cells. Nat. Biotechnol. doi: 10.1038/nbt.2889 PMID: 24752079

27.  Maetzel, D.*, Sarkar, S.*, Wang, H., Abi-Mosleh, L., Xu, P., Cheng, A.W., Gao, Q., Mitalipova, M., Jaenisch, R.# (2014) Genetic and Chemical Correction of Cholesterol Accumulation and Impaired Autophagy in Hepatic and Neural Cells Derived from Niemann-Pick Type C Patient-Specific iPS Cells. Stem Cell Reports doi: 10.1016/j.stemcr.2014.03.014

28.  Dawlaty, M.M., Breiling, A., Le, T. Barrasa M.I., Raddatz, G., Gao, Q., Powell, B.E., Cheng, A.W., Faull, K.F., Lyko, F., Jaenisch R.# (2014) Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev. Cell. 29(1):102-11 PMID: 24735881

29.  Cheng, A.W.*, Wang, H.*, Yang, H, Shi, L., Katz, Y., Theunissen, T.W., Rangarajan, S., Shivalila, C.S., Dadon, D.B., Jaenisch, R.# (2013) Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Research 23(10):1163-71 PMID: 23979020 IF=46.3

30.  Li, Y., Wang, H., Muffat, J., Cheng, A.W., Orlando, D.A., Loven, J., Kwok, S., Feldman, D.A., Bateup, H.S., Gao Q., Hockemeyer, D., Mitalipova, M., Lewis, C.A., Heiden, W.G.V., Sur, M., Young, R.A., Jaenisch, R.# (2013) Global transcriptional and translational repression in human-embryonic-stem-cell-derived Rett Syndrome neurons.Cell Stem Cell 13(4):446-58 PMID: 24094325

31.  Rudenko, A., Dawlaty, M.M., Seo, J., Cheng, A.W., Meng, J., Le, T., Faull, K.F., Jaenisch, R., Tsai, L.H.# (2013) Tet1 is critical for neuronal activity-regulated gene expression and memory extinction. Neuron 79(6):1109-22 PMID: 24050401

32.  Yang, H.*, Wang, H.*, Shivalila, C.S.*, Cheng, A.W., Shi, L., Jaenisch, R.# (2013). One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell 154(6):1370-9 PMID: 23992847

33.  Faddah, D.A., Wang, H., Cheng, A.W., Katz, Y., Buganim, Y., Jaenisch, R.# (2013). Single-cell analysis reveals that expression of nanog is biallelic and equally variable as that of other pluripotency factors in mouse ESCs. Cell Stem Cell 13(1):23-9 PMID: 23827708

34.  Wang, H.*, Hu, Y.C.*, Markoulaki, S., Welstead, C.G., Cheng, A.W., Shivalila, C.S., Pyntikova, T., Dadon, D.B., Voytas, D.F., Bogdanove, A.J., Page, D.C., Jaenisch, R.# (2013). TALEN-mediated editing of the mouse Y chromosome. Nat. Biotechnol. 31(6):530-2 PMID: 23666012

35.  Wang, H.*, Yang, H.*, Shivalila, C.S.*, Dawlaty, M.M., Cheng, A.W., Zhang, F., Jaenisch, R.# (2013). One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153(4):910-8 PMID: 23643243

36.  Lodato, M.A., Ng, C.W.*, Wamstad, J.A.*, Cheng, A.W., Thai, K.K., Faenkel, E., Jaenisch, R., Boyer, L.A.# (2013) SOX2 Co-occupies Distal Enhancer Elements with Distinct POU Factors in ESCs and NPCs to Specify Cell State. PLoS Genet. 9(2):e1003288 PMID: 23437007

37.  Dawlaty, M.M., Breiling, A., Le, T., Raddatz, G., Barrasa, M.I., Cheng, A.W., Gao, Q., Powell, B.E., Li, Z., Xu, M., Faull, K.F., Lyko, F., Jaenisch R.# (2013) Combined Deficiency of Tet1 and Tet2 Causes Epigenetic Abnormalities but Is Compatible with Postnatal Development. Dev. Cell 24(3):310-23 PMID: 23352810

38.  Buganim, Y.*, Faddah D.A.*, Cheng, A.W., Itskovich, E., Markoulaki, S., Gantz, K., Klemm S.L., van Oudenaarden A., Jaenisch, R.# (2012) Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase. Cell 150(6):1209-22 PMID: 22980981

39.  Buganim, Y., Itskovich, E., Hu, Y.-C., Cheng, A.W., Ganz, K., Sarkar, S., Fu, D.D., Welstead, G., Page, D.C., Jaenisch, R.# (2012) Direct Reprogramming of Fibroblasts into Embryonic Sertoli-like Cells by Defined Factors. Cell Stem Cell 11(3):373-86 PMID: 22958931

40.  Welstead, G.G., Creyghton, M.P., Bilodeau, S., Cheng, A.W., Markoulaki, S., Young, R.A., Jaenisch R.# (2012) X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc. Natl. Acad. Sci. U.S.A. 109(32):13004-9 PMID: 22826230

41.  Shapiro, I.M.*, Cheng, A.W.*, Flytzanis, N.C., Balsamo, M., Condeelis, J.S., Oktay, M.H., Burge, C.B.#, Gertler, F.B.# (2011) An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype. PLoS Genet. 7(8):e1002218 PMID: 21876675 (co-first) IF=6.02

42.  Kim, J., Su, S.C., Wang, H., Cheng, A.W., Cassady, J.P., Lodato, M.A., Lengner, C.J., Chung, C.Y., Dawlaty, M.M., Tsai, L.H., Jaenisch R.# (2011) Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell 9(5):413-9 PMID: 22019014

43.  Wong, P., Hattangadi, S.M., Cheng, A.W., Frampton, G.M., Young, R.A., Lodish, H.F.# (2011) Gene induction and repression during terminal erythropoiesis are mediated by distinct epigenetic changes. Blood 118(16):e128-38 PMID: 21860024

44.  Dawlaty, M.M., Ganz, K., Powell, B.E., Hu, Y.C., Markoulaki, S., Cheng, A.W., Gao, Q., Kim, J., Choi, S.W., Page, D.C., Jaenisch, R.# (2011) Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell Stem Cell 5;9(2):166-75 PMID: 21816367

45.  Soldner, F., Laganière, J., Cheng, A.W., Hockemeyer, D., Gao, Q., Alagappan, R., Khurana, V., Golbe, L.I., Myers, R.H., Lindquist, S., Zhang, L., Guschin, D., Fong, L.K., Vu, B.J., Meng, X., Urnov, F.D., Rebar, E.J., Gregory, P.D., Zhang, H.S., Jaenisch, R.# (2011) Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146(2):318-31 PMID: 21757228

46.  Creyghton, M.P.*, Cheng A.W.*, Welstead, G.G., Kooistra, T., Carey, B.W., Steine, E.J., Hanna, J., Lodato, M.A., Frampton, G.M., Sharp, P.A., Boyer, L.A., Young, R.A.#, Jaenisch, R.# (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. U.S.A. 107(50):21931-6 PMID: 21106759 (co-first) IF=12.78, citations (2010-2022): 3736

47.  Lengner C.J., Erwin, J.A.*, Gimelbrant A.A.*, Cheng A.W., Guenther M.G., Welstead G.G., Alagappan R., Frampton M.F., Xu P., Powers D., Barrett C.B., Young R.A., Lee J.T., Jaenisch R.#, Mitalipova, M.# (2010) Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141(5):872-83 PMID: 20471072

48.  Hanna J., Cheng, A.W., Saha K., Kim J.P., Lengner, C.J., Soldner, F., Cassady, J.P., Muffat, J., Carey, B.W., Jaenisch R.# (2010) Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc. Natl. Acad. Sci. U.S.A.107(20):9222-7 PMID: 20442331

49.  Hanna, J.*, Markoulaki, S.*, Mitalipova, M., Cheng, A.W., Cassady, J.P., Staerk, J., Carey, B.W., Lengner, C.J., Foreman, R., Love, J., Gao, Q., Kim, J., Jaenisch, R.# (2009) Metastable Pluripotent States in NOD-Mouse-Derived ESCs. Cell Stem Cell 4(6):513-24 PMID: 19427283

50.  Markoulaki, S.*, Hanna, J.*, Beard, C., Carey, B.W., Cheng, A.W., Lengner, C.J., Dausman, J.A., Fu, D., Gao, Q., Wu, S., Cassady, J.P. and Jaenisch, R.# (2008) Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nat Biotechnol 27(2):169-71 PMID: 19151700

51.  Lo, K.Y., Chin, W. H., Ng, Y. P., Cheng, A. W., Cheung, Z. H and Ip, N. Y.# (2005) SLAM-associated protein (SAP) as a potential negative regulator in Trk signaling. J Biol Chem 280(50):41744-52 PMID: 16223723

1.     Compositions and Methods Related to Nucleic Acid Sensors (WO2024092189)

2.     Multiplex RNA targeting (WO2022187524)

3.     Targeted sequence insertion compositions and methods (WO2022032085)

4.     Activation of lytic genes in cancer cells (WO2021173977)

5.     Live cell imaging of non-repetitive genomic loci (WO2021034585A1)

6.     Artificial RNA-guided Splicing Factors (WO2020069331)

7.     Methods and Compositions for Recruiting DNA Repair Proteins (WO2020041172)

8.     Targeted DNA demethylation and methylation (WO2018053035A1)

9.     Targeted Enhanced DNA Demethylation (WO2018053037A1)

10.  Sequence detection systems (WO2019090287A2)

11.  Transgenic selection methods and compositions (WO2019075200A1)

12.  A Three-component CRISPR/Cas complex system and uses thereof (WO2016148994A1)

13.  Alternatively Spliced mRNA Isoforms as Prognostic and Therapeutic Tools for Metastatic Breast Cancer and Other Invasive/Metastatic Cancers (WO2012116248A1)

14.  Methods of mutating, modifying Or modulating nucleic acid in a cell Or nonhuman mammal (WO2014172470A2)