What We Do
Modern genetics involves the decoding of biological information encoded in organismal genomes and how this DNA code specifies phenotypes, be they biochemical or organismal. Genetics is also concerned with elucidating how various biological processes maintain or alter this code, its mechanism of transmission across generations and its evolution. Human genetics is the specific study of these questions in humans, studies that raise new challenges both because we cannot design genetic crosses as we do in model organisms but also because we can study phenotypes unique to humans, such as mental illness. A particular focus of human genetics is to understand the molecular basis of human disease and, thus, disease pathophysiology.
Our laboratory focuses on the formulation, development and application of genetic, genomic, and computational technologies and perspectives for discovery of genes and mechanisms in a variety of complex (non-Mendelian) human diseases. Specifically, we use a variety of human patients, their families and animal models of these disorders to infer the genetic characteristics of two developmental disorders of neuronal function (Hirschsprung disease, autism) and two late age-at-onset cardiovascular disorders (hypertension, sudden cardiac death). These disorders represent the extremes of genetic action, provide us with different models of non-Mendelian inheritance and articulate the importance of gene regulatory networks in human disease.
Common human diseases, be they birth defects, diabetes, cardiovascular disease, infectious disease, psychiatric illness or neurodegenerative disease, are familial and arise from a combination of genetic and environmental factors. The familial nature of most diseases suggests an underlying genetic susceptibility, but environmental, stochastic and epigenetic factors are also critical. Additional genetic hallmarks of complex disorders are that the underlying mutations are neither necessary nor sufficient for the development of disease, and that these mutations are common in the general population. Current genomic technologies, using the human genomic sequence, comparative sequence from many other vertebrates, a genome-wide map of polymorphic sites and emerging genome-wide maps of functional elements are all critical elements of this genetic dissection and the tools of our trade.
Our overall goals are to develop a paradigm for the genetics of common disease and to assess how genomic information can be used in modern clinical medicine in the era of personalized medicine.