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.
Learn more at www.chem.umass.edu/~chenlab/index.HTML
- BSc (Eng) 1996 and MSc (Eng) 1999 Tianjin University, China
- PhD University of Frankfurt, Germany, 2004
- Postdoctoral Training University of Oxford, UK, 2005-2008