Manolis Kellis, PhD - From Genomics to Therapeutics: Uncovering and Manipulating the Genomic Circuitry of Human Disease; CME (AMA PRA Category 1 CreditsTM) 0.75; ACPE 0.75; CEU (NSGC category 1) 0.075; Attendance CEU 0.75

Wednesday, September 12
3:30 PM - 4:15 PM
Location: Mayo Civic Center Grand Ballroom

Perhaps the greatest surprise of human genome-wide association studies (GWAS) is that 90% of disease-associated regions do not affect proteins directly, but instead lie in non-coding regions with putative gene-regulatory roles. This has increased the urgency of understanding the non-coding genome, as a key component of 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, providing an unbiased view of disease genetics and sometimes re-shaping our understanding of common disorders. For example, we find evidence 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 also combine genetic information with regulatory annotations and epigenomic variation across patients and healthy controls to discover new disease genes and regions with roles in Alzheimer’s disease, heart disease, prostate cancer, and to understand cellular diversity through single-cell RNA-seq and pleiotropic effects by integration with rich intermediate phenotypes and electronic health records. Lastly, we develop systematic technologies for systematically manipulating these circuits by high-throughput reporter assays, genome editing, and gene targeting in human cells and in mice, demonstrating tissue-autonomous therapeutic avenues in Alzheimer’s disease, obesity, and cancer. These results provide a roadmap for translating genetic findings into mechanistic insights and ultimately therapeutic treatments for complex disease and cancer.

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Plenary Speaker :
Manolis Kellis, PhD

Professor
MIT / Broad Institute
Cambridge, Massachusetts

Manolis Kellis, PhD is a Professor of Computer Science 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 PhD 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.

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Manolis Kellis, PhD - From Genomics to Therapeutics: Uncovering and Manipulating the Genomic Circuitry of Human Disease; CME (AMA PRA Category 1 CreditsTM) 0.75; ACPE 0.75; CEU (NSGC category 1) 0.075; Attendance CEU 0.75

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Send Email for Manolis Kellis, PhD - From Genomics to Therapeutics: Uncovering and Manipulating the Genomic Circuitry of Human Disease; CME (AMA PRA Category 1 CreditsTM) 0.75; ACPE 0.75; CEU (NSGC category 1) 0.075; Attendance CEU 0.75