Profiles

The Plath lab has made numerous ground-breaking contributions that have vast impacts on the scientific community. For example, the lab is leading the way in the discovery of mechanisms underlying X-chromosome inactivation by the long non-coding RNA Xist, from identifying how the RNA can target an entire chromosome to defining protein crowding as the mechanism of action by which few Xist molecules can silence the the 1000 genes along the entire X chromosome. The work of the Plath lab on Xist is showing how RNAs can build functional nuclear compartments. The Plath lab also pioneered the understanding of different modes on X-chromosome dosage compensation by XIST RNA in early human development and discovered an unexpected autosomal function for the RNA with implications for understanding the female bias of diseases. The Plath lab also uncovered key mechanisms underlying transcription factor-induced reprogramming of somatic cells to induced pluripotent stem cells that are providing a considerable impetus for understanding and rationally designing cell fate transition. Here we specifically focus on how cis-regulatory enhancer elements are selected and activated by transcription factors. We are also dissecting how genetic variation controls enhancer function.

In addition to continuing the work on X-chromosome dosage compensation, lncRNA function, enhancers and gene regulation, the Plath lab is now also aiming to understand how nutrients that vary with diet can regulate stem cell states and cell fate decisions, particularly those during development, with the ultimate goal to define dietary alterations that enable more accurate models of differentiation in the culture dish or lead to new treatments of pregnancy complications and diseases. We are also using embryonic stem cells, induced pluripotent stem cells and new embryo models to understand the gene regulatory networks underlying cellular specification during development and pathophysiologies.

Often, we develop new single cell genomics technologies and apply them to our diverse biological model systems. In collaboration with the Gomperts lab, we are, for instance, deciphering the difference between the healthy and disease lung at a mechanistic and omics level applying novel multi-comics approaches.