Zhang is a bioengineer focused on developing tools to better understand nervous system function and disease. His lab applies these novel tools to interrogate gene function and study neuropsychiatric diseases in animal and stem cell models. Since joining MIT and the Broad Institute in January 2011, Zhang has pioneered the development of genome editing tools for use in eukaryotic cells – including human cells – from natural microbial CRISPR systems. These tools, which he has made widely available, are accelerating biomedical research around the world.
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. Zhang's work on genome editing traces back to his seminal paper, published in 2010, reporting the first systematic approach of an earlier system, called TALENs, to target specific genes in mammalian cells.
Soon after joining the Broad Institute and MIT, in early 2011 Zhang turned his attention to the CRISPR-Cas system – which researchers in Canada had just demonstrated as being able to create double-stranded breaks in target DNA at precise positions – as a potential tool for improved genome editing. On Oct 5, 2012, Zhang submitted a breakthrough paper which reported the first successful programmable genome editing of mammalian cells using CRISPR-Cas9 (Cong et al. Science 2013). Cong et al. remains the most-cited paper in genome editing.
Since then Zhang’s technique for mammalian genome editing has had enormous impact on experimental science and holds great promise for therapeutic applications. His lab continues to refine and improve upon the CRISPR system and to develop novel genome-engineering technologies aimed at perturbing and editing the genome for disease research.
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Although Zhang is well-known for his pioneering work on CRISPR, he is also widely recognized for developing another breakthrough technology called optogenetics (Zhang et al., Nature Protocols 2010) with Karl Deisseroth at Stanford University and Edward Boyden, now of MIT. Nature Methods named optogenetics its 2010 Method of the Year.
Zhang demonstrated the utility of optogenetics, in which neuronal activity can be controlled with light, by 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.
Zhang grew up in Iowa after moving there with his parents from China at age 11. In high school he spent afternoons working at the Human Gene Therapy Research Institute in Des Moines as part of an academic program. Zhang received his A.B. in chemistry and physics from Harvard College and his Ph.D. in chemistry from Stanford University.
Zhang is a recipient of many awards including the Perl/UNC Prize in Neuroscience (2012, shared with Deisseroth and Boyden), the NIH Director’s Pioneer Award (2012), the National Science Foundation’s Alan T. Waterman Award (2014), the Jacob Heskel Gabbay Award in Biotechnology and Medicine (2014, shared with Jennifer Doudna and Emmanuelle Charpentier), and the Society for Neuroscience Young Investigator Award (2014, shared with Diana Bautista). He has also received technology innovation awards from the McKnight, New York Stem Cell, and Damon Runyon foundations. In 2013 Popular Science named him one of its “Brilliant Ten.” He was named one of the “Top 20 Researchers in 2014” by Nature Biotechnology, which considers the total impact of a scientist's body of published work. Zhang is a founder of Editas Medicine, a 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.
Image: Kent Dayton