From genomics to medicine: Uncovering and targeting the genetic circuits underlying GWAS and cancer

When: 
Thursday, October 1, 2015 - 6:00pm
Room: 
main auditorium
Lecturer(s): 
Manolis Kellis
Lecturer Photo

Perhaps the greatest surprise of human genetic studies is that 90% of disease regions do not affect proteins directly, but instead the circuits that control our genes. This has increased the urgency of mapping the regulatory genome, as a key component for understanding human disease. To address this challenge, we generated maps of genomic control elements across 127 primary human tissues and cell types, and tissue-specific regulatory networks linking these elements to their target genes and their regulators. We have used these maps and circuits to understand how human genetic variation contributes to disease and cancer. The results provide the first unbiased view of disease genetics, sometimes re-shaping our understanding of common disorders. For example, we find that genetic variants contributing to Alzheimer's disease act primarily through immune processes, rather than neuronal processes. We also find that the strongest genetic association with obesity acts via a master switch controlling energy storage vs. energy dissipation in our adipocytes, rather than through the control of appetite in the brain. We have shown that we can manipulate these circuits by genome editing or gene targeting, opening up tissue-autonomous therapeutic avenues for human obesity. Lastly, we show that in addition to dissecting the function of known disease genes, our maps and circuits can be combined with genetic information to discover new genes in cardiovascular disease, type 1 diabetes, and prostate cancer. These results span the spectrum of common, rare, and somatic variants, and illustrate the power and broad applicability of regulatory annotations and circuits for understanding human disease and cancer.

Manolis Kellis is a Professor of Computer Science at MIT, an Institute Member of the Broad Institute of MIT and Harvard, and a member of the Computer Science and Artificial Intelligence Lab at MIT where he directs the MIT Computational Biology Group (compbio.mit.edu). He has helped direct several large-scale genomics projects, including the NIH Roadmap Epigenomics project, the comparative analysis of 29 mammals, the Encyclopedia of DNA Elements (ENCODE) project, and the Genotype Tissue-Expression (GTEx) project. He received the US Presidential Early Career Award in Science and Engineering (PECASE), the NSF CAREER award, the Alfred P. Sloan Fellowship. He obtained his Ph.D. from MIT, where he received the Sprowls award for the best doctorate thesis in computer science. He lived in Greece and France before moving to the US.

This joint meeting of the Boston Chapter of the IEEE Computer Society and GBC/ACM will be held in the main auditorium on the 1st floor of the Broad Institute, corner of Main and Vassar Streets in Cambridge.