We focus on developing chemical tools for the study of cellular processes. In particular, we are interested in investigating peptide/membrane interactions and in elucidating mechanisms of membrane translocation, lysis, transport, and repair. Based on the information we gain, we then develop novel chemical reagents that can better penetrate or kill cells.
Protein delivery methodologies.
We have been interested in understanding how certain peptides penetrate human cells. We have also used this knowledge to develop tools that can deliver proteins into live cells efficiently. It is important because large and hydrophilic proteins cannot typically cross cellular membranes and penetrate cells. This greatly reduces the utility of these molecules in therapeutic or basic research applications. Solving this critical problem should therefore have a dramatic impact in the development of protein-drugs or protein-biosensors as tools to manipulate or monitor intracellular processes.
Recently, we have discovered a class of reagents that allows us to deliver proteins and peptides into cultured live human cells with unprecedented efficiencies and with minimal physiological impact. We are now using these molecules to understand the mechanisms involved in cell penetration. We are also using these molecules as lead compounds for the design of next generation delivery agents.
Delivery of transcription factors and protein biosensors in live cells.
We have developed several strategies to deliver transcription factors into live cells. The long term goal of this project is to use transcription factors to manipulate the behavior of cultured human cells. For instance, certain delivered transcription factors can cause the expansion of hematopoietic stem cells. This approach can in turn potentially improve the success rate of transplantation procedures into patients. Another class of transcription factor can be used to reprogrammed adult cells into induced pluripotent stem cells. Cell-permeable transcription factors might provide a viable strategy to generate cells that could be used for tissue repair.
We are interested in developing cell-permeable biosensors that can report on protein function and cellular processes in real-time. We are interested in using this approach to determine the structure of protein in the context of a live cell by NMR. We are also developing this technology for mapping protein-protein interaction networks in live cells.
Mechanisms of exosomal trafficking.
Exosomes are vesicles produced by human cells. Exosomes can be transferred from one cell to the next, thereby exchanging biological molecules and mediating cell-to-cell signaling. Exosomes have consequently been recognized as an important mechanism by which cells communicate.Given their innate cell penetration capacity, it is also well appreciated that they may provide unprecedented opportunities as drug delivery tools.
By using our new delivery methodology, we have been able to load exosomes with non-genetically encodable cargos and markers. We are currently in the process of using these exosomes to elucidate how exosomes enter host cells.
Antibiotic resistance has become a widespread healthcare problem and new strategies are needed to combat bacterial infections. To address this challenge, we have developed an approach where antimicrobial peptides and light-responsive molecules called photosensitizers are combined to destroy the membrane of bacteria upon light irradiation. By tuning the chemistry of the peptides and of the photosensitizers, we are learning how to kill bacteria with maximal efficiency without causing any harm to human tissue.
The techniques used in the lab include protein engineering, peptide chemistry and live cell fluorescence microscopy