Human Genomics of Infection and Immunity
We use a combination of statistical, functional, and population genomics methods to understand how human genetic diversity translates to phenotypic diversity in the immune system and how this phenotypic diversity affects the clinical outcome of infectious diseases.
Why does our research matter?
Infectious diseases are one of the leading causes of mortality and morbidity worldwide. While many old infections like tuberculosis and HIV still claim millions of lives every year globally. New and emerging infections are also becoming a growing threat due to population growth, urbanization of animal habitats, global warming, and rapid population movement. There is thus a pressing need for a better understanding of infectious disease biology and for the development of innovative diagnoses, preventive, and therapeutic measures to combat ongoing and future outbreaks.
Human genomics of infectious diseases: current state of the field
Previous studies, including my Ph.D. work, have highlighted a key role for human genetic variation in determining the outcome of infectious diseases and show that many disease-associated variants, including the ones affecting infection outcome, can exert their effect by regulation of cellular processes such as gene expression. Together, these studies have established that susceptibility to infectious diseases is a heritable trait, led to the discovery of several key genes that can cause susceptibility to different pathogens, and identified many genomic loci that can modulate the infectious disease risk. However, human genomics of infectious diseases lags behind other complex traits in terms of the number of loci identified. Additionally, for most known infectious diseases risk loci the cellular function of the variants and the biological mechanisms by which they influence disease pathogenesis are not known. Finally, even though the burden of infectious diseases is highest in non-European populations, the majority of large-scale infectious disease genomics studies are done in populations of European ancestry. As shown by my postdoctoral work, ancestry differences can lead to variations in the outcome of complex traits including infectious diseases and might explain why there is little concordance between infectious disease risk loci identified in different populations. There is thus a need to expand human genomics studies of infectious diseases to understudied populations and to use new approaches to connect genetic variants to their molecular function in the disease-relevant context.