Kathrin Plath, Ph.D. 

Kathrin Plath, Ph.D., seeks to understand the fundamental ways genes turn on and off as pluripotent stem cells progress to become a tissue-specific cell type or when certain cell types such as skin cells are reprogrammed back to a pluripotent state. Using biological, molecular, biochemical and genomic approaches, her lab seeks to uncover key information that could improve the efficiency of cell reprogramming, which would significantly advance therapies that aim to use pluripotent stem cells to regenerate or replace damaged or diseased tissue.  

Plath and her UCLA colleagues were among the first scientists to reprogram human skin cells into induced pluripotent stem (iPS) cells, which can self-renew and become any type of human cell. She then used genomic data to discover the role four specialized proteins called transcription factors play in reprogramming skin cells to become iPS cells. Taking this research a step further, Plath and her collaborators used the data they generated to discover a fifth transcription factor that accelerated and enhanced the transition to pluripotency and increased the efficiency of the cell reprogramming process by a hundredfold.

Plath and her collaborators also discovered that female induced pluripotent stem cells retain an inactive X chromosome. Early in embryonic development, all female humans have two active X chromosomes. During normal development, every female embryonic stem cell inactivates one of the X chromosomes. The Plath lab is now focused on understanding how two non-coding RNAs, Xist and Tsix, regulate X chromosome inactivation and how the inactivation process differs between mouse and human development. This work has implications for studying X chromosome-linked diseases such as Rett syndrome and has had a major impact on how researchers think about disease modeling.

The genome's highly complex compact spatial organization determines the fate of cells and can lead to disease if it becomes disorganized or damaged. The Plath lab studies how the genome is folded in the nucleus to fulfill its functions, how this organization changes during iPS cell reprogramming and differentiation, and how genome folding interacts with transcriptional networks and non-coding RNAs. The lab discovered that transcription factors and chromatin regulators play a key role in bringing stretches of DNA together from distant sites in the genome. They are now developing models that comprehensively describe the spatial organization of the genome and the underlying molecular mechanisms. These models are used to explore how the spatial organization contributes to the control of gene expression, and how changes in this organization control cell fate transitions, cellular function and disease processes. 

Plath earned a doctorate degree in biochemistry from Humboldt University in Berlin, Germany and completed post-doctoral fellowships at Harvard Medical School, UC San Francisco and the Whitehead Institute.