Much of humans' evolutionary past is documented in our genomes. Traces of our contact with close relatives like Neandertals, exposure to selective forces like malaria and even the adoption of cultural behaviours such as dairying have all shaped our DNA in readily detectable ways. Looking deeper in time, it is just as straightforward to identify the sequence differences that separate us from our closest living relatives, the chimpanzees, or from the rest of our extended family tree. But this wealth of new data carries one key limitation with it - our ability to consistently identify the actual function and consequence of many of these differences has not kept pace with our ability to identify them. To successfully move beyond the cataloguing of sequence divergence we need new approaches and tools. The field of functional genomics provides such a toolbox. But we must still contend with the complexities of working with critically endangered species, in the case of the great apes, or with human populations that have been either historically exploited by biomedical research, or excluded altogether from it. From comparisons with non-human primates to local adaptation in populations in rural Indonesia and Papua New Guinea that bear traces of our mysterious relatives, the Denisovans, I will present examples of how we can combine anthropological questions with existing functional genomic technologies and pluripotent stem cell technologies to address not only *what* it is that makes us human, but *how* it does so.

Irene Gallego Romero is a Lecturer in Systems Genomics at Melbourne Integrative Genomics and the School of BioSciences at the University of Melbourne. Dr Gallego Romero obtained her PhD in Biological Anthropology from the University of Cambridge, where she focused on identifying signals of recent positive selection and evolutionary adaptation living chiefly in the Indian subcontinent, including their long-standing dairying traditions. She was then awarded a Sir Henry Wellcome Postdoctoral Fellow, which she spent in the laboratory of Yoav Gilad, at the University of Chicago. There she established induced pluripotent cell lines from humans and chimpanzees and demonstrated their validity as model systems for studies of human evolution. Today, her research group uses iPSCs from multiple human populations to examine the biological consequences of evolutionary changes in when and where in an organism certain genes are expressed, and how those changes contribute to human uniqueness.