Professor, Department of Human Genetics and Department of Ecology & Evolution
Director, Institute for Genomics and Systems Biology at the University of Chicago and Argonne National Laboratory
Pritzker fellow, The University of Chicago and the Pritzker School of Medicine
Ph.D. Stanford University, 1998
Fax: (773) 834-2877
The White lab studies the coordinated action of networks of genes that control developmental, disease and evolutionary processes. We have particular focus on discovery of genetic factors that contribute to cancer development and progression, and on building genome-wide models of transcriptional networks. We use an integrated approach that makes use of genome and transcriptome sequencing, large-scale protein-protein and protein-DNA interaction analyses, measurement of chromatin state, systematic RNAi and CRISPR mutational analysis, and high throughput functional analyses of genomic regulatory elements. By applying our methods to both closely and distantly related species, we are investigating how conserved molecular networks control basic developmental processes and how variation in molecular networks translates into variation in organismal phenotypes.
We are also particularly interested in the transcriptional networks controlled by nuclear receptor proteins in development and disease. For example, we have produced genome-wide maps of the entire repertoire of nuclear receptors expressed in breast cancer cells, and this has led to the discovery of previously untargeted nuclear receptors that are promising drug candidates. We then test such candidates in mouse models, and we are attempting to ‘reverse engineer’ the nuclear receptor regulatory networks in breast cancer using a combination of genome-scale data generation, computational techniques and genomic engineering of cell lines and mice. We also have recently built novel algorithms for discovering tumor drivers and tumor risk factors from large-scale sequencing data, such as those available from The Cancer Genome Atlas. In those projects we have identified significantly co-occurring mutations and tested for genetic interactions in cell lines and in patient survival data, we have identified dozens of novel fusion genes and then synthesized them for testing in cell and mouse models, and we have systematically identified germline variants that may contribute to cancer risk and tested their functional roles using CRISPR engineered cell models.
Another focus of the lab is studying genetic regulatory programs that are highly conserved between fly and human. This has led to discoveries such as a role for the protein SPOP in bothDrosophila embryogenesis and human kidney cancer, and to the identification of conserved targets of natural selection during adaptation to hypoxia (low oxygen) in both flies and humans. Related to this comparative work is our lab’s contributions to the ENCODE and modENCODE projects, where we have been systematically comparing the binding patterns of transcription factors genome-wide in flies, worms and humans. Our lab also contributes to the NIH GTEx and psychENCODE projects through our investigations of the relationship between genomic variation and variation in transcript and protein expression.
Finally, we have recently embarked on an ambitious project in pancreatic cancer to co-analyze large numbers of tumor genomes, tens of thousands of electronic medical records, and literature databases to build predictive models of which patients might respond to which treatments. This work is facilitated by the use of patient-derived xenograft models, as well as mouse models developed using the CRISPR Cas9 system. Our goal is to develop algorithmic approaches to rapidly assess a tumor’s genomic and physiological state, then test drugs in mouse models that ultimately can be moved into patients.