Welcome!
The Gilad lab focuses on studying genetic differences between humans and our close evolutionary relatives. Our long term goal is to identify the genetic basis for human specific traits, including genetic variation that underlies higher susceptibility to certain diseases in humans than in other primates.
We are using three main approaches. The first begins with a genome-wide exploration in order to characterize the genetic differences between humans and other primates. For example, recently, Ran Blekhman, a graduate student in the lab, studied differences in gene expression levels between primates, and identified a large number of genes whose regulation evolved under natural selection in different species. Among the set of genes whose regulation evolved under directional selection exclusively in the human lineage, we found enrichments of transcription factors, genes in metabolic pathways, and genes involved in immune response. Subsequent projects in the lab are aimed at characterizing the phenotypes that are affected by changes in the regulation of these genes and pathways.
The second approach is to study the mechanisms of regulatory evolution in primates. To do so, graduate students Carolyn Cain and Russell Bainer characterize the genes that are directly regulated by a set of transcription factors of interest in humans, chimpanzees, and rhesus macaques. The comparison of regulatory interactions across species allows us to map inter-species changes in cis and trans regulatory elements, as well as to identify entire regulatory pathways that have been remodeled in different primate species.
The third approach begins with phenotypes. We focus on phenotypes of interest and study the underlying genetic basis for inter-species differences in phenotypes. For example, Luis Barreiro, a postdoc in the lab, studies differences in immune response between humans and other primates. To do so, Luis works with relevant primary tissue cultures from multiple species and characterizes their immune response at the phenotypic as well as at the gene regulatory level. The long term goal of this project is to characterize the different regulatory networks that underlie the immune response in different primate species.
A different project in the lab is the study of olfactory receptor (OR) genes. We are interested in the evolution of the OR gene family in humans, as well as in their expression and regulation, both in the olfactory epithelium as well as in other tissues (such as testis).