Genetics and Cellular Engineering

Our focus is on using genetics for pathway investigation and engineering synthetic cellular systems for drug discovery. In particular, we are interested in the new capabilities presented by the CRISPR/Cas9 system, both from a target discovery perspective as well as for application in cell engineering for medical therapeutics.

Cell death pathways investigation

Cell death research forms the backbone of our interests. We wish to apply the technologies described below for (1) cell replacement therapy in pathological disease and (2) targeting novel pathways in cancer therapy with biologically engineered therapeutics.

We use forward genetics to identify novel cell death pathways in somatic cells. The CRISPR toolbox has powerful new toys which we employ to investigate new players in apoptotic and programmed non-apoptotic cell death pathways. To support these efforts we have developed in-house software to rapidly identify significant new proteins which accelerates the usage of CRISPR-based screening in novel applications. Newly discovered members are expected to serve as a basis for pharmacological intervention as well as to elucidate control mechanisms in cell physiology.

 

Cell fate engineering

From stem cell to final tissue, cells have seemingly infinite choices in differentiation, but can they be specifically programmed to a certain fate for research or therapeutic application?

We are currently developing technology to guide cell fate choice. We engineer stem cells with relevant transcription factors to “guide” naïve cells to specific terminally differentiated cell fates. The eventual goal is to develop a library of preprogrammed stem cells that autonomously differentiate for different cell replacement therapies.

This project surmounts current cellular differentiation methods by hardwiring fate choices into their DNA. A proof-of-concept channeling stem cells into final fates would enable autonomous, rapid, homogeneous production of virtually any mature cell type, radically advancing biomedical research and therapy.

 

Biosynthetic engineering

In cooperation with the Analytical Biogeochemistry Research Unit we are identifying enzymatic transformations using a meta-genomic platform for drug development.

Many modern drugs are derived from collective millions of years of evolution that utilize enzymes to produce natural bioactive compounds, yet final active pharmaceuticals are painstakingly designed by chemistry. This project seeks to uproot the tedious diversification process normally performed by medicinal chemistry and transfer it into cells. A "Living Library" of unique enzymes that derivatize a primary starting substance will revolutionize drug development as well as create a continuous production source.