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  Our research program is largely driven by our scientific interest on a broad view of how cells/tissues function in response to manmade materials. We use the approach of supramolecular self-assembly to build dynamic, functional nanostructures using de novo designed peptides and peptide-polymer conjugates as the molecular building blocks. Fundamentally we aim to understand the effect of multiple synergistic non-covalent interactions on the self-assembly and their dynamics and how to gain structural control across multiple length scales down to the molecular level. We are interested in understanding how cells “sense” the dynamics of these materials and how the supramolecular assembly influences various cellular processes, such as the cellular uptake pathway, intracellular trafficking and other cell signaling activities. We believe the answers to the above questions will provide important insights and guidance for the design of advanced functional materials for a variety of biomedical applications. For more detailed project description, please click on Research and follow our recent Publications.
     

Front cover story about cell penetrating peptides. In this work, we demonstrated a simple yet powerful strategy to assemble single-chain cationic peptides into macromolecular filamentous nanostructures with dramatically improved membrane activity, stability and transfection efficiency.

Click here for more infomation.

 

Principal Investigator

Dr. He Dong
hdong@clarkson.edu
Postdoc, UC Berkeley 2012
Postdoc, Emory University 2009
PhD, Rice University 2008

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Current Group Members

Dawei Xu (Since Fall 2013)
PhD Student
xud@clarkson.edu
Master, Chongqing University 2013

Linhai Jiang (Since Fall 2013)
MS Student
jiangl@clarkson.edu
Bachelor, Donghua University 2013

 

 

 

Maureen Hoen (Since Fall 2014)
Undergraduate Student

Brendan J. Elmore(Since Summer 2015)
Undergraduate Student

Louis DeRidder (Since Summer 2015)
Undergraduate Student

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Alumni

Miao Yang
Graduate student (2012-2014)

Zach Marchese
Graduate student (2012-2013)

Brian Boateng(Summer 2015)
Undergraduate Student

Madeleine Grandon (Summer 2015)
Undergraduate Student

Derek Dustin
Undergraduate student (2013-2015)

Shawn Beaulieu (Spring 2014)

Kristen Harvey(Summer 2014)

Keira Henry(Summer 2014)

Megan Borland
Freshman (2012)

Patrick Bankich
Senior (2013)

Victorial Duvell
Freshman (2012)

Peter Lamothe
Sophomore (2013)

Panarin Chinavinjkul
Junior(2012-2013)

Supramolecular Assembly of De novo Designed Cationic Peptides for Anticancer and Antimicrobial Therapies

Rational design and engineering of synthetic macromolecules with natural peptide/protein-like activities have great implications on modern cancer therapy and infectious disease treatments. This work aims to develop a novel class of supramolecular polymers to mimic (1) protein transduction domain with potent cell penetrating activity and (2) host defense peptide with broad-spectrum antimicrobial activity. We have demonstrated that fibrous morphology dramatically improves cell transduction activity and leads to exceptional anticancer drug efficacy in mammalian cell lines. Meantime, a delicate balance between materials assembly and disassembly is required to achieve optimal broad-spectrum antimicrobial activity. While current study demonstrated fundamental concepts, further work will be focused to gain a comprehensive understanding of the structure-activity connections between molecular composition, supramolecular chemistry and biological activity. The acquired knowledge will help build up a solid foundation for the rational design of supramolecular nanostructured materials, in particular nanofiber-based materials to probe various biological processes.
 

 

 

Programmed Self-assembly Through Symmetry Control

Natural proteins have evolved on their own to self-associate into distinct nanostructures and networks through non-covalent interactions. The self-association is largely controlled by the generic geometric conformation and oligomerization states of protein subunits, which defines the “symmetry” of individual protein building block and further the shape, size and dimensionality of large protein assembly. Our research is inspired by the design principle of fusion proteins to self-assemble into symmetry controlled single object or extended network. We aim at developing novel supramolecular nanostructures to mimic large protein assemblies through the self-assembly of two short, orthogonally folded protein motifs which are chemically linked together. The acquired knowledge can help us design future biomimetic nanomaterials with superb functionality for a variety of biomedical and environmental applications such as vaccine delivery, cellular scaffolds and molecular separation

 

Nanostructured Bioconjugates and Hybrid Materials as Extracellular Matrix Mimetics (ECM)

The function of natural ECM is determined by both the hierarchical structure and mechanical property of protein scaffolds. We are interested in the fabrication of a range of hybrid materials based on the self-assembly of peptide-polymer bioconjugates with inorganic metals. The hybrid materials would be expected to combine the well-defined protein hierarchical structure, tunable mechanical properties and controlled inorganic composition and nanostructures to suit various needs in 3-D cell culture and tissue regeneration.

 

Journal Papers

2016  
29 Linhai Jiang, Dawei Xu, Kevin E. Namitz, Michael S. Cosgrove, Reidar Lund, He Dong, "Protein-like nanoparticles based on orthogonal self-assembly of chimeric peptides", Small, 2016, in press. (Click here to read)
   
 
   
28 Dawei Xu, Linhai Jiang, Louis DeRidder, Brendan Elmore, Maurish Bukhari, Qiang Wei, Damien S.K. Samways, He Dong, "Membrande activity of a supramolecular peptide-based chemotherapeutic enhancer", Mol. Biosyst., 2016, in press. (Click here to read)
   
 
   
27 Dennis A. Delgado, Katelynne Doherty, Qinghui Cheng, Hyeongeun Kim, Dawei Xu, He Dong, Christof Grewer Wei Qiang, "Distinct membrane disruption pathways induced by the 40-residue beat-amyloid peptides", J. Biol. Chem., 2016, 291, 12233-12244. (Click here to read)
   

26

Xiaobo Liu, Mouna Marrakchi, Dawei Xu, He Dong, Silvana Andreescu, "Biosensors based on modularly designed synthetic peptides for recognition, detection and live/dead differentiation of pathogenic bacteria", Biosensors and Bioelectronics, 2016, 80, 9-16. (Click here to read)
   
 
   
25 Dawei Xu, Qian Ran, Yang Xiang, Linhai Jiang, Britannia Smith, Fadi Bou-Abdallah, Reidar Lund, Zhongjun Li , He Dong, "Toward hemocompatible self-assembling antimicrobial nanofibers: understanding the synergistic effect of supramolecular structure and PEGylation on hemocompatibility", RSC Advances, 2016, 6, 15911-15919. (Click here to read)
   
 
   
2015  
24 Linhai Jiang, Dawei Xu, Timothy J. Sellati, He Dong, "Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological property dictate antimicrobial activity", Nanoscale, 2015, 7, 19160-19169. (Click here to read)
   
 
   
23 Dawei Xu, Derek Dustin, Linhai Jiang, Damien S.K. Samways, He Dong, "Designed filamentous cell penetrating peptides: probing supramolecular structure-dependent membrane activity and transfection efficiency", Chem. Comm., 2015, 51, 11757-11760. (Front Cover)
   
 
   
22 He Dong, Reidar Lund, Ting Xu, "Micelle stabilization via entropic repulsion: balance of force directionality and geometric packing of subunit", Biomacromolecules, 2015, 16, 743-747. (Click here to read)
   
 
   
21
Dawei Xu, Linhai Jiang, Anju Singh, Derek Dustin, Miao Yang, Ling Liu, Reidar Lund, Timothy Sellati, He Dong, "Designed supramolecular filamentous peptides: balance of nanostructure, cytotoxicity and antimicrobial activity", Chem. Comm., 2015, 51, 1289-1292. (Click here to read)
   
 
   
2014  
20
Nikhil Dube, Jia W. Seo, He Dong, Jessica Y. Shu, Reidar Lund, Lisa M. Mahakian, Katherine W. Ferrara, Ting Xu, "Effect of alkyl length of peptide-polymer amphiphile on cargo encapsulation stability and pharmacokinetics of 3-helix micelles", Biomacromolecules, 2014, 15, 2963-2970.
   
 
   
19
Geng Li, Jun Wu, Xu Qin, Jianhui Zhu, Kodandaraman Viswanathan, He Dong, P. Somasundaran, Richard A. Gross, "Chemo-enzymatic routes to lipopeptides and their colloidal properties", Langmuir, 2014, 30(23), 6889-6896
   
 
   
18
Miao Yang, Dawei Xu, Linhai Jiang, Lin Zhang, Derek Dustin, Reidar, Lund, Ling Liu, He Dong, "Filamentous supramolecular peptide-drug conjugates as highly efficient drug delivery vehicles", Chem. Comm., 2014, 50, 4827-4830. (Click here to read)
   
 
   
17
Bin Cao, Linlin Li, Haiyan Wu, Qiong Tang, Bingbing Sun, He Dong, Jiang Zhe, Gang Cheng, "Zwitteration of dextran: a facile route to intergrate antifouling, switchability and optical transparency into natural polymers", Chem. Comm., 2014, 50, 3234-3237.
   
 
   
2013  
16 Nikhil Dube, Jessica Y. Shu, He Dong, Jai W. Seo, Elizabeth Ingham, Azadeh Kheirolomoom , Pin-Yuan Chen, John Forsayeth, Krystof Bankiewicz, Katherine W. Ferrara, Ting Xu, “Evaluation of doxorubicin-loaded 3-helix micelles as nanocarriers”, Biomacromolecules, 2013, 14(10): 3697-3705
 
 
 
 
Before joining Clarkson:
15
He Dong, Jessica Y. Shu, Nikhil Dube, Yufei Ma, Matthew V. Tirrell, Kenneth H. Downing, Ting Xu, “3-helix micelles stabilized by polymer springs”, J. Am. Chem. Soc., 2012, 134, 11807-11814.
14
He Dong, Nikhil Dube, Jessica Y. Shu, Jai W. Seo, Lisa M. Mahakian, Katherine W. Ferrara, Ting Xu, “Long circulating micelles based on helix-bundle forming peptide-polymer conjugates”. ACS Nano2012, 6, 5320-5329.
13
He Dong, Xuezheng Song, Yi Lasanajak, Richard D. Cummings, Elliot L. Chaikof, “Facile Construction of Fluorescent Peptide Microarrays: One-step fluorescent derivatization of sub-microscale peptide aldehydes for selective terminal immobilization”. Analytical Biochemistry 2010, 398(1), 132-134.
12
Lorenzo Aulisa, He Dong, Jeffrey, D. Hartgerink. “Self-assembly of multidomain peptides: Sequence variation allows control over crosslinking and viscoelasticity”. Biomacromolecules 2009, 10(9), 2694-2698 .
11
He Dong, Sergey, E. Paramonov, Jeffrey, D. Hartgerink, “Self-assembly of alpha-helical coiled coil nanofibers”, J. Am. Chem. Soc. 2008, 130, 13691-13695.
10
Hoo-Wok, Jun, Sergey, E. Paramonov, He Dong, Jeffrey, D. Hartgerink, “Enzyme-mediated degradation of peptide-amphiphile nanofiber networks”, Journal of Biomaterial Research, Polymer Ed, 2008, 19, 665-676
9
He Dong, Sergey, E. Paramonov, Lorenzo, Aulisa, Erica Bakota, Jeffrey, D. Hartgerink “Self-assembly of multi-domain peptides: Balancing molecular frustration controls conformation and nanostructure”, J. Am. Chem. Soc. 2007, 129, 12468-12471.
8
He Dong, Jeffrey, D. Hartgerink, “Investigation of role of hydrophobic clusters on coiled coils in inducing alpha to beta secondary structural conversion”, Biomacromolecules2007, 8(2), 617-623
7
He Dong, Jeffrey, D. Hartgerink, “Short helical coiled coil homodimer and heterodimer”,Biomacromalecules2006, 7(3), 691-695
6
He Dong, Aijun Tong, “Syntheses of steroid-based molecularly imprinted polymers and their molecular recognition study”, Spectrochimica Acta A2003, 59(2), 279-284
5
He Dong, Aijun Tong, Longdi Li, “A molecular imprinting-based fluorescent chemosensor for histamine using zinc(II)-protoporphyrin as a functional monomer”, Analytical Chimica Acta,2002, 456, 31-37
4
He Dong, Aijun Tong, Longdi Li, “Synthesis of a fluorescent molecularly imprinted polymer and its recognition property for histamine”, Chem. J. Chinese University2002, 23(6), 1081-1021
3
He Dong, Aijun Tong, “A new fluorescent molecularly imprinted polymer for the selective binding of histamine”, Analytical Sciences2002, 17, a295-a298
2
YuHui Zhang, He Dong, Aijun Tong, “Molecular design and molecular recognition with fluorescent receptors”, Analytical Lab2002, 21(5), 93-99
1
Aijun Tong, Qingyi Yang, He Dong, Longdi Li, “Recognition of amine, amino acids by zinc protoporphyrin in water”, Analytical Sciences2002, 17, a207-a210
 

Book Chapter

He Dong,Virany, M. Yowono, Jeffrey, D. Hartgerink. “Supramolecular polymerization of peptides and peptide derivatives”. Molecular Recoginition and Polymers. Published by Wiley.2008, 359-393

Peptide Synthesizer

 

CD

Prep-HPLC

 

Analytical-HPLC

Lyophilizer

 

Plate reader

Ultra-speed centrifuge

 

 

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This website is updated by Linhai on Aug 26th, 2016.