The University of Massachusetts Amherst

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Min Chen

Assistant Professor

Current Research
My group is developing a switchable bacterial toxin for drug delivery across the cell membrane. This toxin, engineered to become active at specific cell sites, can be potentially used as a therapeutic to treat cancers. Another ongoing project in my lab is to create a biosensor toolkit which can quickly evolve and adapt to detect any target protein molecules. This technology could lead to major advances in biomarker and warfare agent detection.

Pore-forming toxins (PFTs) and peptides can form large water-filled openings in the cell’s membrane that disrupt the delicate balance of solutes between the interior and exterior of the cell, leading to cell death. These openings also provide a direct path for drug molecules to enter the cell. We are engineering protease or light activitable PFTs based on E. coli cytolysin A (ClyA). ClyA proteins are switched on at the tumor site by tumor-specific proteases or light radiation. These ClyA kill tumor cells by a synergistic approach that combines the ClyA toxin’s cytolytic activity and the delivery of therapeutic drugs in cancer therapy.

The central goal of our biosensing project is to create a nanopore sensor that can be tuned to specifically detect virtually any protein. The sensor is an engineered form of outer membrane protein G (OmpG) from E. coli. The loops that connect the strands of OmpG’s β-barrel are either appended with a ligand or lengthened with a recognition sequence to create the specific sensing elements. A library of OmpG mutants will be selected for novel target affinity directly from the bacteria using a high-throughput screening and enrichment approach.

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Academic Background

  • BSc (Eng) 1996 and MSc (Eng) 1999 Tianjin University, China
  • PhD University of Frankfurt, Germany, 2004
  • Postdoctoral Training University of Oxford, UK, 2005-2008
Pham B, Eron S, Hill ME, Li X, Fahie MA, Hardy JA and Chen M*: Detection of caspase protease using a OmpG nanopore. 2019, Biophys J, 117: 1-12.
Wolfe AJ, Gugel JF, Chen M and Movileanu L: Kinetics of Membrane Protein-Detergent Interactions Depend on Protein Electrostatics. 2018, J Phys Chem B, 122 (41):9471–9481.
Bo L, Stokes C, Fahie MA, Chen M, Golovchenko JA and Hau LV: Protein Dynamics of a form-fitting protein in a nanopore: Avidin in ClyA. 2018, Biophysical J, 115 (5): 801-808.
Wolfe AJ, Gugel JF, Chen M and Movileanu L: Detergent Desorption of Membrane Proteins Exhibits Two Kinetic Phases. 2018, J Phys Chem Lett, 9:1913–1919.
Fahie MA, Liang L#, Avelino AR#, Pham B, Limpikirati P, Vachet RW and Chen M*: Disruption of the open conformation of the transmembrane α-helical barrel in the β-tongue deletion mutants of Cytolysin A. Sci Rep, 2018, 8:3796.
Perez-Rathke A§, Fahie MA§, Chisholm C, Liang J* and Chen M*: Mechanism of OmpG pH-dependent gating from loop ensemble and single channel studies. J Am Chem Soc, 2018, 140 (3): 1105–1115.
Li X, Huang J, Holden MA and Chen M*: Peptide mediated membrane transport of macromolecular cargo driven by membrane asymmetry. 2017, Anal Chem, 89(22):12369-12374.
Wolfe AJ, Si W, Zhang F, Blanden AR, Hsueh Y-C, Gugel JF, Pham B, Chen M, Loh SN, Rozovsky S, Aksimentiev A and Movileanu L: Quantification of Membrane Protein-Detergent Complex Interactions. 2017, J Phys Chem B, 121 (44):10228-10241.
Wolfe AJ, Hsueh Y-C, Blanden AR, Mohammad MM, Pham B, Thakur AK, Loh AK, Chen M and Movileanu L: Interrogating Detergent Desolvation of Nanopores. Anal Chem, 2017, 89(15):8013-8020.
Lin M, Zhang G, Fahie MA, Morgan LK, Chen M, Keiderling TA, Kenney LJ and Liang J: Computational Design and Experimental Characterization of Monomeric Porin OmpGF, BBA - Biomembranes, 2017, 1859(7):1180-1189.
Contact Info

Department of Chemistry
865 Lederle Graduate Research Tower
710 North Pleasant Street
Amherst, MA 01003-9292

(413) 545-0683