Research

Some scientific goals that motivate us

Genome Editing Technologies

Altering the genetic code of life has become trivial, as researchers can readily modify nucleic acid sequences in living cells and organisms. Such capabilities have been made possible by decades of research and development of genetic engineering technologies. We have a deep interest in building, characterizing, and optimizing new genome editing technologies to further enable their wide application across a variety of scientific disciplines.

Protein Engineering

So, we can edit genomes.
But are the technologies that we use as efficient, useful, and safe as they can be?
CRISPR enzymes evolved over millenia to combat bacterial pathogens, not to function at the whim of a scientist. As such, they're not equipped with all of the designer characteristics that we want + need for genome editing. To close this gap, we use molecular evolution systems to impart desirable properties into CRIPSR nucleases, with the hope of developing more robust, specific, and broadly targetable technologies.

Molecular Medicines

A major goal of our lab is to learn about the challenges that face the effective clinical translation of genome editing technologies. Situated in the Center for Genomic Medicine at Massachusetts General Hospital, our group is collaborating with several other laboratories to leverage novel technologies to both create disease models, and to develop preclinical strategies to correct pathogenic sequences. We're pursuing these efforts with the hope that the promise of genome editing technologies can be realized for the treatment of human diseases.

Overcoming Mutation Heterogeneity

Few human diseases are caused by the same mutation in a gene across all patients - meaning that most genetic diseases result from sporadic mutations at various positions within a gene. Although it is possible to correct private mutations that are specific to individual patients, this genetic heterogeneity imposes challenges for the development of therapies given the impracticality of scaling bespoke edits to all patients (due to both research and regulatory barriers). To overcome these bottlenecks, new editing approaches are needed that move beyond mutation-specific edits and instead towards exon or gene sized replacements.