About Us

What we do

Our current research program is focused on addressing two distinct, but complementary, questions. The first is to decipher the role of gene regulatory changes in the evolution of uniquely human traits, particularly the expansion and elaboration of the human cerebral cortex. Our initial efforts targeted a class of elements that we and others first characterized over a decade ago: Human Accelerated Regions (HARs). These elements are highly conserved across species but show many human-specific changes, suggesting they encode uniquely human functions of potentially large effect. We have since expanded the scope of our work to globally identify human-specific regulatory innovations using experimental methods. Our current research is aimed at understanding the phenotypes these regulatory changes specify using humanized mouse models, massively parallel genetic screens, and cellular models of primate neurodevelopment.

More recently, we have expanded our interests further to identify gene regulatory mechanisms underlying a human neurodevelopmental phenotype of enormous public health significance: autism. Our current research is focused on characterizing regulatory networks disrupted in autism using mouse and cellular models of brain development. This work is highly synergistic with our studies of human brain evolution, drawing on the same intellectual and experimental resources we have established over the last decade.

Our history

Our laboratory has made multiple contributions over the last decade. We were the first to discover that HARs encode transcriptional enhancers with human-specific functions in the developing embryo (Prabhakar et al. 2008). We then developed methods to map and quantify the activity of gene regulatory elements during mammalian organogenesis, and to identify their gene targets (Cotney et al. 2012 and DeMare et al. 2013). Building on this work, we implemented comparative epigenetics approaches to identify uniquely human regulatory innovations by direct analysis of developing human and nonhuman tissues. This work, described in two major studies, discovered thousands of promoters and enhancers that have gained activity in during human limb and neocortical development (Cotney et al. 2013 and Reilly et al. 2015). These studies have also identified biological pathways in limb and cortical development potentially altered by human-specific regulatory changes, providing the basis for understanding their effects using genetic and experimental models. We also leveraged these findings to understand general principles of developmental enhancer evolution and identify specific regulatory innovations contributing to the emergence of the mammalian neocortex (Emera et al. 2016). We also demonstrated that a major autism risk gene, CHD8, directly regulates other autism-associated genes during neurodevelopment, providing an entry point for deciphering gene regulatory networks contributing to autism risk (Cotney et al. 2015).

Data availability

Primary data associated with our publications are available through public repositories under the accession numbers listed in those papers. We also maintain a separate web server to share data that cannot be easily distributed through an established repository. Those data are available at noonan.ycga.yale.edu.

Our collaborators

Our funding support

We are supported by grants from the National Institute of General Medical Sciences, the Kavli Foundation, and the Simons Foundation Autism Research Initiative.