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Dong Lab

Publications

2022


Chen B, Basak S, Chen P, Zhang C, Perry K, Tian S, Yu C, Dong M, Huang L, Bowen ME, Jin R.  Structure and conformational dynamics of Clostridioides difficile toxin A. Life Sci Alliance. 5(6). [PDF]


Xiong X, Tian S, Yang P, Lebreton F, Bao H, Sheng K, Yin L, Chen P, Zhang J, Qi W, Ruan J, Wu H, Chen H, Breault DT, Wu H, Earl AM, Gilmore MS*, Abraham J*, Dong M* (2022). Emerging enterococcus pore-forming toxin with MHC/HLA-1 as receptors. Cell, 185:1-15.  [PDF]


Tian S, Liu Y, Appleton E, Wang H, Church M. G., Dong M (2022). Targeted intracellular delivery of Cas13 and Cas9 nucleases using bacterial toxin-based platforms. Cell Reports, 38:110476.   [PDF]




2021


Marreddy RKR, Olaitan AO, May JN, Dong M, Hurdle JG. Ebselen Not Only Inhibits Clostridioides difficile Toxins but Displays Redox-Associated Cellular Killing. Microbiol Spectr. 9(2):e0044821. [PDF]



Liu Z, Zhang S, Chen P, Tian S, Zeng J, Perry K, Dong M, Jin R. Structural basis for selective modification of Rho and Ras GTPases by Clostridioides difficile toxin B. Sci Adv. 7(43):eabi4582. [PDF]



Zhou Y, Li D, Luo J, Chen A, Li X, Pan Z, Wan L, He L, Li D, Li Y, Dong M, Tao L.  Sulfated glycosaminoglycans and low-density lipoprotein receptor mediate the cellular entry of Clostridium novyi alpha-toxin. Cell Res. 31(8):935-938.  [PDF]



Kowarschik S, Schöllkopf J, Müller T, Tian S, Knerr J, Bakker H, Rein S, Dong M, Weber S, Grosse R, Schmidt G. Yersinia pseudotuberculosis cytotoxic necrotizing factor interacts with glycosaminoglycans. FASEB J. 35(7):e21647. [PDF]



Shao DD, Straussberg R, Ahmed H, Khan A, Tian S, Hill RS, Smith RS, Majmundar AJ, Ameziane N, Neil JE, Yang E, Al Tenaiji A, Jamuar SS, Schlaeger TM, Al-Saffar M, Hovel I, Al-Shamsi A, Basel-Salmon L, Amir AZ, Rento LM, Lim JY, Ganesan I, Shril S, Evrony G, Barkovich AJ, Bauer P, Hildebrandt F, Dong M, Borck G, Beetz C, Al-Gazali L, Eyaid W, Walsh CA.  A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features. Genet Med. 23(6):1158-1162.  [PDF]



Thaker H, Zhang J, Miyashita SI, Cristofaro V, Park S, Hashemi Gheinani A, Sullivan MP, Adam RM, Dong M (2021). Knockin mouse models demonstrate differential contributions of synaptotagmin-1 and -2 as receptors for botulinum neurotoxins. PLoS Pathog.17(10):e1009994.    [PDF]



Liu Y, Tian S, Thaker H, Dong M. Shiga Toxins: An Update on Host Factors and Biomedical Applications. Toxins (Basel).13(3).   [PDF]



Thaker H, Zhang S, Diamond DA, Dong M. Beyond botulinum neurotoxin A for chemodenervation of the bladder. Curr Opin Urol. 31(2):140-146.  [PDF]



Pan Z, Zhang Y, Luo J, Li D, Zhou Y, He L, Yang Q, Dong M, Tao L. Functional analyses of epidemic Clostridioides difficile toxin B variants reveal their divergence in utilizing receptors and inducing pathology. PLoS Pathog.17(1):e1009197.  [PDF]



Chen P, Zeng J, Liu Z, Thaker H, Wang S, Tian S, Zhang J, Tao L, Gutierrez CB, Xing L, Gerhard R, Huang L, Dong M*, Jin R* (2021). Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection. Nat Commun. 12(1):3748.   [PDF]



Dong M, Stenmark P (2021). The Structure and Classification of Botulinum Toxins. Handb Exp Pharmacol. 263:11-33. [PDF]



Blum TR, Liu H, Packer MS, Xiong X, Lee PG, Zhang S, Richter M, Minasov G, Satchell KJF, Dong M*, Liu DR* (2021). Phase-assisted evolution of botulinum neurotoxin proteases with reprogrammed specificity. Science, 371:803   [PDF]


Science Perspective: https://science.sciencemag.org/content/371/6531/782.long

News reports:           https://www.genengnews.com/news/evolved-proteases-selectively-cleave-target-sequences-unlock-potential-of-proteome-editing/

https://www.sciencedaily.com/releases/2021/02/210225082527.htm

https://www.linkresearcher.com/theses/060a8949-a775-4027-ba4e-d8a89b38dfbf




Miyashita S, Zhang J, Zhang S, Shoemaker CB, Dong M (2021). Delivery of single-domain antibodies into neurons using a chimeric toxin-based platform is therapeutic in mouse models of botulism. Science Translational Medicine, 13:eaaz4197.   [PDF]


Science In Depth: https://science.sciencemag.org/content/371/6525/113/tab-pdf

News reports: https://www.sciencedaily.com/releases/2021/01/210108142136.htm

https://www.news-medical.net/news/20210106/Non-toxic-versions-of-botulism-toxins-can-deliver-therapeutic-antibodies-to-treat-botulism.aspx

https://biotechscope.com/fighting-botulism-with-botulism/

https://www.genengnews.com/insights/trojan-horse-antidotes-designed-to-neutralize-lethal-botulinum-toxin/




2020


Mansfield MJ, Tremblay BJM, Zeng J, Wei X, Hodgins H, Worley J, Bry L, Dong M*, Doxey AC*. (2020)  Phylogenomics of 8,839 Clostridioides difficile genomes reveals recombination-driven evolution and diversification of toxin A and B. PloS Pathogens, 16(12):e1009181   [PDF]



Henkel D, Tatge H, Schöttelndreier D, Tao L, Dong M, Gerhard R. Receptor Binding Domains of TcdB from Clostridioides difficile for Chondroitin Sulfate Proteoglycan-4 and Frizzled Proteins Are Functionally Independent and Additive. Toxins (Basel).12(12).   [PDF]



He A, Ma L, Huang Y, Zhang H, Duan W, Li Z, Fei T, Yuan J, Wu H, Liu L, Bai Y, Dai W, Wang Y, Li H, Sun Y, Wang Y, Wang C, Yuan T, Yang Q, Tian S, Dong M, Sheng R, Xiang D. CDKL3 promotes osteosarcoma progression by activating Akt/PKB. Life Sci Alliance. 3(5).    [PDF]



Lam KH, Tremblay JM, Vazquez-Cintron E, Perry K, Ondeck C, Webb RP, McNutt PM, Shoemaker CB, Jin R.  Structural Insights into Rational Design of Single-Domain Antibody-Based Antitoxins against Botulinum Neurotoxins. Cell Rep. 2020 Feb 25;30(8):2526-2539.e6.  [PDF]



Tian S, Liu Y, Wu H, Liu H, Zeng J, Choi MY, Chen H, Gerhard R, Dong M (2020). Genome-wide CRISPR screen identifies semaphorin 6A and 6B as receptors for Paeniclostridium sordellii toxin TcsL. Cell Host and Microbe, 27:782-792. PMC7228847.    [PDF]



Yin L, Masuyer G, Zhang S, Zhang J, Miyashita S, Burgin D, Lovelock L, Coker SF, Fu T, Stenmark P*, Dong M* (2020). Characterization of a membrane binding loop leads to engineering botulinum neurotoxin B with improved therapeutic efficacy. PloS Biology, 17;18(3):e3000618.   [PDF]



Martínez-Carranza M, Blasco P, Gustafsson R, Dong M, Berntsson RP, Widmalm G, Stenmark P (2020). Synaptotagmin Binding to Botulinum Neurotoxins. Biochemistry. 59:491-498.  [PDF]




2019


Tao L**, Tian S*, Zhang J*, Liu Z, Robinson-McCarthy L, Miyashita S, Breault D.T., Gerhard R, Oottamasathien S, Whelan S.P.J., Dong M**  (2019) Sulfated glycosaminoglycans and low-density lipoprotein receptor contribute to Clostridium difficile toxin A entry into cells. Nature Microbiology. 4:1760.  [PDF]



Garland M, Babin BM, Miyashita S, Loscher S, Shen Y, Dong M, Bogyo M (2019). Covalent modifiers of botulinum neurotoxin counteract toxin persistence. ACS Chem Biol. 14:76-87.  [PDF]



Shen Y, Wu SY, Rancic V, Aggarwal A, Qian Y, Miyashita S, Ballanyi K, Campbell RE, Dong M (2019). Genetically encoded fluorescent indicators for imaging intracellular potassium ion concentration. Commun. Biol. 2:18 doi: 10.1038/s42003-018-0269-2.   [PDF]



Mansfield MJ, Wentz TG, Zhang S, Lee EJ, Dong M**, Sharma SK**, Doxey AC** (2019). Bioinformatic discovery of a toxin family in Chryseobacterium piperi with sequence similarity to botulinum neurotoxins. Scientific Report, 9:1634   [PDF]



Elliott M, Favre-Guilmard C, Liu SM, Maignel J, Masuyer G, Beard M, Boone C, Carre D, Kalinichev M, Lezmi S, Mir I, Nicoleau C, Palan S, Perier C, Raban E, Zhang S, Dong M**, Stenmark P**, Krupp J** (2019). Engineered botulinum neurotoxin B with improved binding to human receptors has enhanced efficacy in preclinical models. Science Advances. 5:eaau7196   [PDF]



Košenina S, Masuyer G, Zhang S, Dong M*, Stenmark P* (2019). Crystal structure of the catalytic domain of the Weissella oryzae botulinum-like toxin. FEBS Lett. 593(12):1403-1410.   [PDF]



Tian S, Wu Q, Zhou B, Choi MY, Ding B, Yang W, Dong M (2019). Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex. Cell Rep. 28(10):2517-2526.e5.   [PDF]



Dong M, Masuyer G, Stenmark P (2019). Botulinum and tetanus neurotoxins. Annual Review of Biochemistry, 88:811.  [PDF]




2018


Tian S, Muneeruddin K, Choi MY, Tao L, Bhuiyan RH, Ohmi Y, Furukawa K, Furukawa K, Boland S, Shaffer SA, Adam RM, Dong M (2018). Genome-wide CRISPR screens for Shiga toxins and Ricin reveal Golgi proteins critical for glycosylation. PloS Biology, 16:e2006951   [PDF]



Chen P*, Tao L*, Wang T, Zhang J, He A, Lam K, Liu Z, He X, Perry K, Dong M**, Jin R** (2018). Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B. Science, 360:664.* co-corresponding authors.   [PDF]



Chen P, Tao L, Liu Z, Dong M, Jin R. Structural insight into Wnt signaling inhibition by Clostridium difficile toxin B. FEBS J. 286(5):874-881.   [PDF]



Zhang S, Lebreton F, Mansfield MJ, Miyashita S, Zhang J, Schwartzman JA, Tao L, Masuyer G, Carranza M, Stenmark P, Gilmore MS, Doxey A*, Dong M* (2018). Identification of a botulinum neurotoxin-like toxin in a commensal strain of Enterococcus faecium, Cell Host and Microbe, 23:169-176. * co-corresponding authors.   [PDF]



Masuyer G, Zhang S, Barkho S, Shen Y, Henriksson L, Kosenina S, Dong M*, Stenmark P* (2018). Structural Characterization of the catalytic domain of botulinum neurotoxin X – high activity and unique substrate specificity.  Scientific Reports, 8:4518. * co-corresponding authors.   [PDF]



Gustafsson R, Zhang S, Masuyer G, Dong M, Stenmark P. Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding. Toxins (Basel).10(4).   [PDF]




2017


Chevalier A, Silva DA, Rocklin G, Hicks DR, Vergara R, Murapa P, Bernard SM, Zhang L, Lam KH, Yao G, Bahl CD, Miyashita S, Goreshnik I, Fuller JT, Koday MT, Jenkins C, Colvin T, Carter L, Bohn A, Bryan CM, Velasco DA, Stewart L, Dong M, Huang X, Jin R, Wilson IA, Fuller DH, Baker D (2017). Massively parallel de novo protein design for targeted therapeutics. Nature (article), 550:74-79  [PDF]



Zhang S, Berntsson R, Tepp WH, Tao L, Johnson EA, Stenmark P*, and Dong M* (2017). Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC, Nature Communications, 8, 1637. * co-corresponding authors.  [PDF]



Huang N, Pishesha N, Mukherjee J, Zhang S, Deshycka R, Sudaryo V, Dong M, Shoemaker CB, Lodish HF (2017). Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin. Nature Communications, 8:423, PMC5583347. [PDF]



Yao G, Lam KH, Weisemann J, Peng L, Krez N, Perry K, Shoemaker CB, Dong M, Rummel A, Jin R. A camelid single-domain antibody neutralizes botulinum neurotoxin A by blocking host receptor binding. Sci Rep. 7(1):7438.  [PDF]



Tao L*, Peng L*, Berntsson R, Liu S, Park S, Yu F, Boone C, Palan S, Beard M, Chabrier P, Stenmark P**, Krupp J**, Dong M** (2017). Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors. Nature Communications 8:53. * co-first authors; ** co-corresponding authors. [PDF]



Zhang S, Masuyer G, Zhang J, Shen Y, Lundin D, Henriksson L, Miyashita S, Martinez-Carranza M, Dong M*, Stenmark P* (2017). Identification and characterization of a novel botulinum neurotoxin. Nature Communications 8:14130. * co-corresponding authors.   [PDF]




2016


Tao L, Zhang J, Meraner P, Tovaglier A, Wu X, Gerhard R, Zhang X, Stallcup WB, Miao J, He X, Hurdle JG, Breault DT, Brass AL, Dong M (2016). Frizzled proteins are colonic epithelial receptor for C. difficile toxin B. Nature (article, 538: 350-355, doi:10.1038/nature19799).  [PDF]


Research Highlight” Nature Reviews Microbiology

http://www.nature.com/nrmicro/journal/v14/n11/full/nrmicro.2016.152.html



Yao G*, Zhang S*, Mahrhold S*, Lam K, Stern D, Bagramyan K, Perry K, Kalkum M, Rummel A**, Dong M**, Jin R**(2016). N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A. Nature Structure and Molecular Biology, 23, 656-662. * co-first author; ** co-corresponding authors.  [PDF]


“News and Views” Nature Structure & Molecular Biology, 2016, 23:619-621.




2009-2014


Lee K, Zhong X, Gu S, Kruel AM, Dornet MB, Perry K, Rummel A, Dong M, Jin R (2014). Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. Science, 344:1405-10.   [PDF]



Peng L, Adler M, Demogines A, Borrell A, Liu H, Tao L, Tepp WH, Zhang SC, Johnson EA, Sawyer SL and Dong M (2014).Widespread sequence variations in VAMP1 across vertebrates suggest a potential selective pressure from botulinum neurotoxins. PLoS Pathogens 10(7):e1004177, PMCID: PMC 4092145.   [PDF]



Berntsson RP-A, Peng L, Svensson LM, Dong M, Stenmark P (2013). Crystal Structures of Botulinum Neurotoxin DC in Complex with Its Protein Receptors Synaptotagmin I and II. Structure, 21:1602. PMC3803103.   [PDF]



Berntsson RP-A, Peng L, Dong M, Stenmark P (2013). Structure of Dual Receptor Binding to Botulinum Neurotoxin B. Nature Communications, 4:2058. PMC3752466.   [PDF]



Peng L, Liu H, Ruan H, Tepp WH, Stoothoff WH, Brown RH, Johnson EA, Yao WD, Zhang SC, and Dong M. Cytotoxicity of Botulinum Neurotoxins Reveals Essential Neuronal Plasma Membrane SNAREs. Nature Communications, 2013; 4:1472.  [PDF]


Harvard News report: http://hms.harvard.edu/news/new-wrinkle-botox-3-26-13

Faculty of 1000 recommended



Peng L, Berntsson RP-A, Tepp WH, Pitkin RM, Johnson EA, Stenmark P, and Dong M (2012). Botulinum neurotoxin D-C uses synaptotagmin I/II as receptors and human synaptotagmin II is not an effective receptor for type B, D-C, and G toxins. J. Cell Science,125:3233  [PDF]


Comments in J. Cell Science (2012), 125:e1306

2012 Roger T. Kelleher Award from the New England Primate Center for outstanding research paper



Wu Y, Gu Y, Morphew MK, Yao J, Yeh FL, Dong M, Chapman ER. All three components of the neuronal SNARE complex contribute to secretory vesicle docking. J Cell Biol. 198(3):323-30.



Wang D, Zhang Z, Dong M, Sun S, Chapman ER, Jackson MB. Syntaxin requirement for Ca2+-triggered exocytosis in neurons and endocrine cells demonstrated with an engineered neurotoxin. Biochemistry. 50(14):2711-3.



Peng L, Tepp WH., Johnson EA., Dong M (2011). Botulinum neurotoxin D uses synaptic vesicle protein SV2 and gangliosides as receptors. PLoS Pathogen, 7:e1002008. PMCID: PMC3068998   [PDF]


2010 Roger T. Kelleher Award from the New England Primate Center for outstanding research paper



Yeh FL, Dong M, Yao J, Tepp WH, Lin G, Johnson EA, Chapman ER. SV2 mediates entry of tetanus neurotoxin into central neurons. PLoS Pathog. 6(11):e1001207.



Liu H, Dean C, Arthur CP, Dong M, Chapman ER. Autapses and networks of hippocampal neurons exhibit distinct synaptic transmission phenotypes in the absence of synaptotagmin I. J Neurosci. 29(23):7395-403.




Publications in Edwin Chapman’s lab, University of Wisconsin and HHMI:


Dong M, Liu H, Tepp WH, Johnson EA, Janz R, Chapman ER (2008).“Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons”, Mol. Bio. Cell, 19(12):5226  


Dong M, Tepp WH, Liu H, Johnson EA, Chapman ER (2007). “Mechanism of BoNT/B and G entry into hippocampal neurons”, J. Cell Biol., 179(7):1511


Chai Q*, Arndt JW*, Dong M*, Tepp WH, Johnson EA, Chapman ER, Stevens RC (2006). “Structural basis of cell surface receptor recognition by botulinum neurotoxin B”, Nature, 444 (7122) :1096  (*equal contribution)


   -- Comments in: Nature (2006), Dec 21;444(7122):1019-20


                            Nature Struct. Mol. Biol. (2007), Jan;14(1):9-10


Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, Chapman ER (2006). “SV2 is the protein receptor for botulinum neurotoxin A”, Science, 312(5773):592


   -- Comments in: Science (2006), Apr 28;312(5773):540-1“A Neuronal Receptor for Botulinum Toxin”.


                           Nature Reviews Neuroscience (2006), vol.7, pp.420-421“Illicit entry”.


                           Chemical Biology (2006), vol.1, pp.117..  “Botox on the Brain”.


                           Physiology (2006), vol.21, pp. 229“Highlights”


Dong M, Tepp WH, Johnson EA, Chapman ER (2004). “Using fluorescent sensors to detect botulinum neurotoxin activity in vitro and in living cells”, PNAS (USA), 101(41): 14701


    -- This study has led to the creation of a biotech company, BioSentinel LLC, to commercialize the inventions.


Dong M, Richards DA, Goodnough MC, Tepp WH, Johnson EA, Chapman ER (2003). “Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells”, J.Cell Biol., 162(7):1293


    --  Comments in : Journal of Cell Biology (2003), vol.162, pp.1178. “How to block Botox”.


Lewis JL, Dong M, Earles CA, Chapman ER (2003). “The transmembrane domain of syntaxin 1A is critical for cytoplasmic domain protein-protein interaction”, J. Biol. Chem., 276(18):15458