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
Fahie M, Romano F, Chisholm C, Heuck AP, Zbinden M and Chen M: A non-classical assembly pathway of Escherichia coli pore forming toxin cytolysin A. J Biol Chem, 2013, 288(43):31042-31051
Zhuang T, Chisholm C, Chen M and Tamm LK: NMR-based conformational ensembles explain pH-gated opening and closing of OmpG channel. J Am Chem Soc, 2013, 135(40):15101-15113
Chen M, Khalid S, Sansom M and Bayley H: Outer membrane protein G: engineering a quiet pore for biosensing. Proc Natl Acad Sci U S A 2008, 105: 6272-6277 (cover article). Comment in: Eisenberg B: Engineering channels: atomic biology. Proc Natl Acad Sci U S A 2008 Apr 29;105:6211-6212.
Chen M, Abele R and Tampé R: Functional non-equivalence of ABC signature motifs in the transporter associated with antigen processing. J Biol Chem 2004, 279:46073-46081.
Chen M, Abele R and Tampé R: Peptides induce ATP hydrolysis at both subunits of the transporter associated with antigen processing. J Biol Chem 2003, 278:29686-29692.
Contact Info

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

(413) 545-0683