NOMIS researcher James Noonan, who has made critical and novel contributions to the fields of human evolutionary genetics and neurodevelopment, was recently appointed the Albert E. Kent Professor of Genetics and Professor of Neuroscience, effective immediately. He is co-leading the Deciphering the Evolutionary Origins of Human Brain Uniqueness project.
Noonan received his B.S. in biology and English literature from the State University of New York at Binghamton in 1997, and his Ph.D. in genetics from Stanford University School of Medicine in 2004. He completed a postdoctoral fellowship in the Genomics Division at Lawrence Berkeley National Laboratory from 2004 to 2007. In 2007, he was recruited to Yale as assistant professor and was promoted to associate professor in 2013, and professor in 2021. He has a secondary appointment in Yale’s Department of Neuroscience.
Noonan’s research program is focused on deciphering the role of gene regulatory changes in the evolution of uniquely human traits. This work addresses a central hypothesis in human evolution, proposed more than 40 years ago: that changes in the level, timing, and location of gene expression account for biological differences between humans and other primates. Noonan has discovered thousands of human-specific genetic changes that alter gene expression and regulation, and by pioneering novel genetic models, his lab has begun to reveal how human-specific regulatory changes alter developmental traits. His work has provided key insights into the genetic origins of human biological uniqueness and has driven the rise of a new field: human evolutionary developmental biology.
Noonan’s seminal research discovered two classes of gene regulatory elements implicated in human evolution. The first are Human Accelerated Regions (HARs), which encode transcriptional enhances which are highly conserved across species and show many human-specific sequence changes (Science 2006, Science 2008). Using humanized mouse models, he has shown that HARs alter developmental gene expression and drive the evolution of novel phenotypes. As an example, he recently showed that one HAR altered expression of a transcription factor that has a role in limb development, possibly contributing to changes in skeletal patterning in human limb evolution (Nature Communications, 2022). These findings provide mechanistic insight into how HARs modified gene expression in human evolution. Using massively parallel assays, he has also comprehensively characterized the effect of thousands of human-specific sequence changes in HARs on their activity during neurodevelopment (Proceedings of the National Academy of Sciences, 2021)
He also identified thousands of human-specific changes in enhancer activity by direct analysis of developing human and nonhuman tissues. These loci, termed “Human Gain Enhancers” (HGEs), have gained activity in the developing human limb (Cell, 2013) and cerebral cortex (Science, 2015). These studies identified the biological pathways in limb and cortical development likely altered by human-specific regulatory changes, providing the basis for understanding their effects using genetic and experimental models.
Noonan has also contributed substantially to the educational programs of Yale School of Medicine, revolutionizing its graduate training landscape and empowering experimental genetics research across many labs at Yale. He designed the first course in genomics in the medical school more than 12 years ago, serving hundreds of students and faculty with the skills required to excel at the frontier of modern biomedical science. His training efforts have helped to set the standards of genomic research at Yale and ensured that the university remains a world leader in genomics.
Go to this Yale News release
James P. Noonan
Albert E. Kent Professor of Genetics and Professor of Neuroscience
Deciphering the Evolutionary Origins of Human Brain Uniqueness
NOMIS RESEARCH PROJECT