Judith Zaugg

 

Judith B Zaugg
European Molecular Biology Laboratory
Heidelberg, Germany

Website: www.zaugg.embl.de
Twitter: @zauggj

 

Regulatory Genomics: from Basic Biology to Disease Mechanisms

Phenotypic variation (including disease) across individuals has two main sources: genetic variation across individuals, and variation in environmental exposures. In the past 20 years we have made tremendous efforts in mapping common genetic variants to complex traits and diseases. Yet, the majority of these disease-associated variants lie in the non-coding part of the genome, which makes is very difficult to understand the underlying molecular mechanisms. For the environmental variation we still know very little, except that part of it will be stored in epigenetic signatures. Therefore, to gain a mechanistic understanding of phenotypic variation and potentially identify molecular intervention points of disease, it is essential to understand how genetic variants affect gene regulation, and to generate models that predict how external signals and epigenetics contribute to overall variability. Here I will present our recent work on regulatory network models that aim at integrating environmental signaling with genetic and epigenetic variation in regulatory elements to understand complex phenotypes. I will show applications of our models to pulmonary arterial hypertension, ageing of the bone marrow niche and leukemia. Overall, our integrative computational tools with a focus on gene regulation provide a powerful approach to gain mechanistic insights into complex biological processes.

Short bio

Judith Zaugg started her group in Computational and Regulatory Genomics at EMBL in 2014 (www.zaugg.embl.de). Since 2018 she is also co-leading research group on Stem Cell-Niche Networks within the framework of the Molecular Medicine Partnership Unit (MMPU) at the University hospital Heidelberg. She studied chemical and molecular biology at ETH in Zurich, obtained her PhD at Cambridge University and EMBL-EBI, and went to Stanford for her postdoctoral research where she was co-leading studies on epigenetic variation across individuals, and discovered that many so-called epigenetic marks do in fact have a genetic basis (Grubert et al). Her group at EMBL focuses on computational biology in epigenetics and gene regulation, developing computational tools (e.g. differential transcription factor activity diffTF – Berest et al) to understand basic gene regulatory principles (e.g. how CTCF mediated chromatin looping is involved in splicing – Ruiz-Velasco et al) and epigenetic mechanisms underlying complex diseases. Her MMPU group focuses on understanding the interaction between the stem cell populations within the hematopoietic niche, and how aging and blood cancer affect these interactions (e.g. Garg et al).

In addition to her research, Judith Zaugg is an organiser of the bi-yearly Multiomics data integration conference at EMBL and the EMBL ATAC-Seq course.

Selected publications:

Berest et al. (2019): Quantification of differential transcription factor activity and multiomic-based classification into activators and repressors: diffTF. BioRxiv doi:10.1101/368498 (Cell Reports in press) https://git.embl.de/grp-zaugg/diffTF

Ruiz-Velasco et al. (2017): CTCF-mediated chromatin loops between promoter and gene body regulate alternative splicing across individuals: Cell Systems 5 (6), 628-637

Garg et al. (2019) Hepatic leukemia factor is a novel leukemic stem cell regulator in DNMT3A, NPM1, and FLT3-ITD triple-mutated AML. Blood. https://doi.org/10.1182/blood.2018862383

Grubert et al. Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions. Cell. 162 (5): 1051-1065