Kathrin Plath, Ph.D.

Plath’s innate curiosity about fundamental biological processes has led to significant contributions to the fields of stem cell biology, gene regulation, epigenetics and regenerative medicine. Her research combines computational, molecular, imaging, genomics, biochemical and cell biological approaches to understand the gene regulatory mechanisms underlying cellular identity, plasticity and cell fate changes. She is particularly focused on cell transitions to and from the pluripotent state, as well as X chromosome inactivation, a process in which one of the two X chromosomes in female cells is “turned off” to balance gene expression.

Plath and fellow center members Amander T. Clark, Ph.D., William Lowry, Ph.D., and April Pyle, Ph.D., were among the first scientists to use genomic data to pinpoint exactly how four specialized proteins called transcription factors are able to change the identity of skin cells to create induced pluripotent stem cells. Building on this work, she collaborated with Jason Ernst, Ph.D., to identify a fifth transcription factor that accelerated and enhanced tissue-specific cells’ transition to pluripotency — increasing the efficiency of the cell reprogramming process by a hundredfold. These discoveries are critical to researchers’ efforts to effectively model, understand and treat many life-limiting diseases using stem cell-derived tissues or cells.

She further examines the epigenetic changes underlying cell fate changes through the lens of X chromosome inactivation. This process induces silencing and heterochromatin formation on an entire chromosome through the function of the long-noncoding RNA Xist. Her discoveries in this area provide insights into the role of long-noncoding RNAs and how heterochromatin forms during differentiation and is reset during reprogramming. 

Plath also found that transcription factors and chromatin regulators are crucial for bringing distant DNA segments together in the genome. She is currently working on models to fully explain this spatial genome organization and its molecular mechanisms, which could uncover how genome spatial organization affects gene expression control and influences cell fate changes, cellular function and diseases.