Seminar • Bioinformatics • Integrative Models of 3D Nuclear DNA Organization

Please note: This seminar will take place in DC 1304.

Anupama Jha, Postdoctoral Scholar
Department of Genome Sciences, University of Washington

DNA is compactly packed in the nucleus of a cell; around 2 meters of human DNA is stored in a 10 μm nucleus. Evidence suggests that 3D genome organization facilitates long-range interactions between transcriptional regulatory elements, which control tissue-agnostic and tissue-specific gene activation and epigenetic silencing. My long-term research goal is to study how DNA sequence variations influence the 3D genome organization in humans and across mammalian evolution, how variations in genome organization impact transcriptional and post-transcriptional gene regulation across human tissues, and how this regulatory infrastructure is misregulated in cancer.

In this talk, I will cover previous work constructing sequence-to-function models for different steps of gene regulation, including 3D genome architecture, gene expression and alternative splicing in normal tissues and cancers. We identified several regulatory elements implicated in gene regulation by interpreting these models using existing and novel techniques. These include transcription factors and G-quadruplexes implicated in trans-contacts and RNA-binding proteins implicated in tissue-specific alternative splicing. Toward the end, I will outline my vision for developing novel computational methods for large-scale multi-omics data analysis.  These methods can potentially yield actionable insights into cell-specific gene regulation in heterogeneous healthy and diseased individuals.

Bio: Anupama Jha obtained her Ph.D. in computer science from the University of Pennsylvania, where she was advised by Yoseph Barash. During her Ph.D., she studied transcriptomics using deep learning. She developed one of the early splicing code models to predict tissue-specific alternative splicing from sequence-derived features.

In March 2021, she joined the lab of Bill Noble in the Department of Genome Sciences at the University of Washington to study 3D genome architecture. During her postdoc, she developed fibertools, a popular method for characterizing chromatin accessibility from long-read sequencing. Her current focus is to learn the sequence determinants of 3D cis and trans chromosomal interactions in the human genome and the preservation of these structures across mammalian evolution using computational tools. This work is funded by NHGRI through a K99/R00 Pathway to Independence award.