In Sickness and in Health: Gene Regulation and 3D Chromatin Organization in Disease

Friday, May 26, 2017 -
2:00pm to 3:00pm
The FUNG Auditorium
Ferhat Ay

Institute Leadership Assistant Professor of Computational Biology

Vaccine Discovery Department

La Jolla Institute for Allergy & Immunology

In Sickness and in Health: Gene Regulation and 3D Chromatin Organization in Disease

The field of regulatory genomics has recently witnessed significantly increased interest in the three-dimensional genome structure in the nucleus, catalyzed by the development of sequencing based conformation capture techniques. By profiling genomic proximities on a genome-wide scale (e.g., Hi-C), these techniques demonstrated that regions far apart in linear DNA sequence may form functional and stable long-range loops to interact with each other in the 3D space. Our lab is broadly interested in the systematic analysis of these proximities in human and other genomes to uncover links between genome structure and function. More specifically, in this talk, I will first discuss our published and unpublished work on studying the dynamic nuclear organization of the deadliest human malaria parasite (Plasmodium falciparum). Our work revealed that the parasite has a complex genome architecture shaped around precisely regulating its virulence genes and that this architecture goes through holistic changes in correlation with the parasite’s overall transcriptional activity during its complex life cycle. We also identified a sexual stage-specific domain on a P. falciparum chromosome that is demarcated by a nearby sex-specific transcription factor that is essential for the parasite’s sex determination. Next, I will talk about our recent study of CD4 T-cells from a cohort of donors to further characterize gene regulation of an asthma risk associated locus that harbors SNPs, which reconfigure local chromatin interactions. We showed that this reconfiguration correlates with overexpression of a gene in individuals carrying risk alleles and, in turn, in negative regulation of cytokine production. Finally, I will talk about our computational work in developing methods for identifying statistically significant interactions between regulatory elements and for characterizing genomic rearrangements in cancer cells such as amplifications, deletions, translocations and inversions from chromatin conformation capture data. 

Ferhat Ay received his B.S. degrees in Computer Engineering and Mathematics both from Middle East Technical University (METU), Turkey in 2007. He received his PhD degree from the Department of Computer Science at the University of Florida in 2011. He subsequently joined the Department of Genome Sciences at the University of Washington as a Computing Innovation Fellow awarded by Computing Research Association and NSF. Ferhat's primary research areas are bioinformatics, computational biology, epigenomics and regulatory genomics. Ferhat works on understanding the relationship between three-dimensional genome architecture and gene regulation in different human diseases such as cancer and asthma, and in different eukaryotic pathogens such as Plasmodium falciparum and Plasmodium knowlesi through data integration, computational modeling and statistical approaches. He was a Research Assistant Professor in the Department of Preventive Medicine-Health and Biomedical Informatics at Northwestern University in 2015 before establishing his lab at the La Jolla Institute for Allergy and Immunology (LJI) as the Institute Leadership Assistant Professor in 2016.