We study how gene regulation has shaped human evolution and diseases
WHAT WE SEEK TO UNDERSTAND
In the animal kingdom, many human adaptations stand out. Our brain size has increased by 3-fold, we have transitioned to upright walking, and our learning period has become particularly long. These adaptations were pivotal to our success as a species, but they also brought with them new diseases, including Alzheimer’s disease, epithelial cancers, preterm labor and more. How did this process occur? How did we become human? and why did these extraordinary adaptations come with such a high price tag?
Gene regulatory changes (i.e., changes to the level, timing, and tissues in which a gene is expressed) are thought to be the main drivers of evolution. However, our understanding of how gene regulatory changes shape human evolution is limited. In our lab, we study how gene regulatory changes have differentiated us from our closest relatives: the extinct Neanderthals and Denisovans, and the extant great apes. We use and develop a wide range of tools and resources, both computational and experimental: from ancient Neanderthal and Denisovan DNA, through computational approaches for extraction of phenotypic information from genetic data, to generating human-ape hybrid cells.
HOW HUMAN-SPECIFIC DISEASES EMERGE
Evolution is a game of net fitness. If a new evolutionary change is overall disadvantageous it is unlikely to spread in the population. This raises the question: why do diseases (and particularly common diseases) even exist? In our lab, we seek to shed light on the interplay between evolution and disease. We use hybridization approaches (human-ape hybrid cells and knockout-wildtype mouse cells) to identify gene regulatory changes that have been adaptive in some respects, but detrimental in others.
IDENTIFYING THE GENETIC CHANGES THAT
PROPELLED HUMAN ADAPTATION
Humans differ from their closest relatives in many traits. However, we know very little about the genetics underlying these differences. In our lab, we seek to uncover the genetic basis of key human adaptations. We focus on gene regulatory changes, which are thought to underlie most of the phenotypic differences between closely related species. We use human-ape hybrid cells, massively parallel reporter assays and mouse models to link sequence changes to the gene regulatory changes they underlie and ultimately - to divergent phenotypes.
PREDICTING PHENOTYPES FROM GENETIC
One of the biggest challenges in genetics today is to infer phenotypes from genetic data. Achieving this is critical in assessing disease susceptibility, improving crops, reconstructing the anatomy of extinct organisms, and more. In our lab, we develop new methods and tools to push the frontiers of phenotypic inference from genomic data. We combine gene regulatory data with models of gene-phenotype interactions to develop new approaches for phenotypic prediction. We then apply these approaches to identify genes underlying phenotypic divergence between individuals and species.