Compbio.mit.edu - MIT Computational Biology Group - Kellis Lab at MIT and Broad Institute

Variation and Disease: Translating genetic findings into therapeutics remains an unsolved challenge, partly because in 93% of cases, disease-associated common variants do not disrupt proteins directly, but instead alter their genomic control elements. Our group develops and uses epigenomic maps of regulatory elements, and cellular circuits linking them to their regulators and target genes, in order to understand how human genetic variation contributes to disease and cancer. We have developed resources and methods for studying how genetic variation impacts gene expression, regualtory region activity, cellular phenotypes, and ultimately human disease. We have applied these methods to obesity, Alzheimer's disease, cardiovascular traits, psychiatric disorders, and cancer, resulting in multiple insights. In addition to dissecting these circuits, we have used gene manilations and genome editing to reverse the phenotypic signatures of disease from risk and non-risk individuals, paving the way for genomics-based therapeutics.