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Kellis Lab biotechnology

Learn how we seek to understand the mechanistic basis of human disease, using computational and experimental techniques.

About Us

Variation and Disease

A major focus of our lab is understanding the effects of genetic variation on molecular phenotypes and human disease. We develop methods for integrating diverse functional genomic datasets of transcription, chromatin modifications, regulator binding, and their changes across multiple conditions to interpret genetic associations, identify causal variants, and predict the effects of genetic perturbations. (genomics, biotechnology, human genome project)


Genome Interpretation

To recognize the molecular basis of human biology and disease, we need a comprehensive understanding of the human genome. This requires computational methods for genome interpretation which can systematically intepret the functional elements encoded in the 4-letter DNA code. For this purpose, we have developed methods for the comprehensive annotation of proteins, RNAs and regulatory control elements encoded in the human genome.

Gene regulation

Beyond the primary sequence of the genome, it has been recognized that a wide variety of post-translational modifications play key roles in genome function, cellular differentiation, and human disease.  We are developing new methods using genome-wide maps to discover recurrent and spatially-coherent combinations of marks, or 'chromatin states'. 


We also develop data integration methods to systematically characterize chromatin state function, revealing diverse classes of enhancers, promoters, and insulators, which we used to discover new functional elements, to study chromatin dynamics across cell types and development, and to reveal motifs and regulators governing epigenetic changes in development, differentiation and disease.

Decoding a Genomic Revolution

Ongoing Projects

Variation and Disease

Understanding the effects of genetic variation on molecular phenotypes and human disease. We develop methods for integrating diverse functional genomic datasets of transcription, chromatin modifications, regulator binding, and their changes across multiple conditions to interpret genetic associations, identify causal variants, and predict the effects of genetic perturbations.

More on: Variation and Disease

Genome Interpretation

We have developed comparative genomics methods which can directly discover diverse functional genomic elements based on their characteristic patterns of evolutionary change across related species. We have used such signatures in the human, fly, and yeast genomes to recognize protein-coding genes and exons, RNA genes and structures, microRNAs and their targets, and diverse classes of regulatory elements. 

More on: Genome Interpretation, Protein-coding Genes, Non-coding RNAs

Disease Area

The disease areas that we're focusing on include cancer, metabolic, neurodegenerative, psychiatric, and immune disorders. 


We've developped specific domain expertise in obesity, type 2 diabetes, Alzheimer's Disease, immune cells, Schizophrenia and cancer. 

Gene regulation

Epigenomics, chromatin regulation, and developmental programs. Beyond the primary sequence of the genome, a wide variety of post-translational modifications play key roles in genome function, cellular differentiation, and human disease. . We have developed new methods for addressing these challenges, using genome-wide maps to discover recurrent and spatially-coherent combinations of marks, or 'chromatin states'. We also developed data integration methods to systematically characterize chromatin state function, revealing diverse classes of enhancers, promoters, and insulators, which we use to discover new functional elements, to study dynamics across cell types and development, and to reveal motifs and regulators governing epigenetic changes in development, differentiation and disease.

More on: Chromatin - Regulatory Motifs - Biological Networks

Epigenomics

With the recent availability of genome-wide maps of histone modifications, we have developed new methods for the systematic discovery of recurrent combinations of chromatin marks, or "chromatin signatures," which we found to be associated with very specific types of functional elements, including diverse classes of enhancers, promoters, and insulators. We have used these signatures to discover new elements, including novel non-coding RNA genes, and to systematically study the dynamics of chromatin state across tissues and during development, and to discover the sequence elements and grammars governing those changes. We are currently also exploring the role of small non-coding RNAs in the establishment, maintenance, and targeting of chromatin state.

More on: Epigenomics - Regulatory RNAs

Genome evolution

We have also developed methods to study systematic differences between the species compared, and uncovered important evolutionary mechanisms for the emergence of new functions. To further understand the evolutionary processes leading to new functions, we developed a phylogenomic framework for studying gene family evolution in the context of complete genomes, revealing two largely independent evolutionary forces, dictating gene- and species-specific mutation rates. De-coupling these two rates also allowed us to develop the first machine-learning approach to phylogeny, resulting in drastically higher accuracies than any existing phylogenetic method.   

More on: Evolution - Phylogenomics.

Variation and Disease

Understanding the effects of genetic variation on human 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.


We develop methods for integrating diverse functional genomic datasets of transcription, chromatin modifications, regulator binding, and their changes across multiple conditions to interpret genetic associations, identify causal variants, and predict the effects of genetic perturbations.

Learn More

You can find our papers grouped by area under Ongoing Projects