Feng Zhang is a core member of the Broad Institute of MIT and Harvard, as well as an investigator at the McGovern Institute for Brain Research at MIT and an assistant professor at MIT with a joint appointment in the Departments of Brain and Cognitive Sciences and Biological Engineering.
Zhang applies synthetic biology approaches to study nervous system function and disease. His lab also develops and applies novel tools using a combination of animal and stem cell models. Since joining the Broad Institute and McGovern in January 2011, Zhang has developed technologies for editing the genome and has engineered a new genome-editing tool for use in eukaryotic cells – including human cells – from natural bacterial CRISPR systems. This engineered CRISPR-Cas9 system allows researchers to mutate or change the expression of genes in living mammalian cells.
Zhang leverages CRISPR and other methodologies to study the role of genetic and epigenetic mechanisms underlying diseases, specifically focusing on disorders of the nervous system. He is especially interested in complex disorders, such as psychiatric and neurological diseases, that are caused by multiple genetic and environmental risk factors and which are difficult to model using conventional methods. Zhang’s methods are also being used in the fields of immunology, clinical medicine, cancer biology, and other areas of research. Zhang’s long-term goal is to develop novel therapeutic strategies for disease treatment.
As a graduate student at Stanford University working with Karl Deisseroth, Zhang helped to develop a methodology called optogenetics, in which neuronal activity can be controlled with light, and he demonstrated its utility in studying neural circuits in the brain. Zhang later served as a Junior Fellow at Harvard’s Society of Fellows and collaborated with Paola Arlotta and George Church on using synthetic biology to study the patterns of gene activity during brain development, a topic with implications for neurological and psychiatric problems. While a Junior Fellow, Zhang engineered the TAL effector (TALE) system — programmable DNA binding proteins that can be easily customized to target novel DNA sequences — for targeting and activating genes of mammalian genomes.
With the start of his independent lab in January 2011 at the Broad and MIT, Zhang looked to develop new genome-editing tools better suited for his investigations at both institutions. Zhang began researching the scientific literature on the CRISPR system and, synthesizing evidence from existing foundational studies of the natural system dating back to its discovery in 1987, recognized that it had the potential to overcome many of the limitations of existing genome-editing methodologies. Zhang immediately set out to harness the CRISPR system, only found in prokaryotic cells, for genome editing in mammalian/human cells.
Through a series of experiments, Zhang’s group successfully demonstrated the application of Cas9 proteins harnessed from both Streptococcus pyogenes and Streptococcus thermophilus along with appropriate CRISPR RNA guides for genome editing in human cells, publishing their work in the journal Science on January 3, 2013 (Cong et al., Science 2013). His laboratory continues to refine and improve upon the CRISPR/Cas9 system and to develop novel genome-engineering technologies aimed at perturbing and editing the genome for disease research.
In the interest of sharing CRISPR/Cas9 resources widely and openly, Zhang’s team has already shared CRISPR reagents and tips with thousands of laboratories, and continues to make all of its CRISPR tools available to the academic research community directly and via the plasmid-sharing website Addgene. These tools are openly shared as soon as possible with researchers the world over. Addgene has distributed CRISPR plasmids deposited by Zhang more than 13,000 times since his team’s first publication in January 2013, enabling researchers around the world to make new discoveries, reported in several hundreds of articles based on work with these tools.
Zhang is a recipient of many awards including the Perl/UNC Prize in Neuroscience (2012, shared with Karl Deisseroth and Edward Boyden), the NIH Director’s Pioneer Award (2012), the National Science Foundation’s Alan T. Waterman Award (2014), and the Jacob Heskel Gabbay Award in Biotechnology and Medicine (2014, shared with Jennifer Doudna and Emmanuelle Charpentier).
Zhang is a founder of Editas Medicine, a transformative genome-editing company founded by world leaders in the fields of genome editing, protein engineering, and molecular and structural biology, with specific expertise in CRISPR/Cas9 and TALE technologies.
Zhang received his A.B. in chemistry and physics from Harvard College and his Ph.D. in chemistry from Stanford University, and he is grateful to all of his mentors for their training and guidance.