
Bio
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.
Publications
- TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoidsPublished in Stem Cell Reports on Thursday, September 29, 2022
- Xist nucleates local protein gradients to propagate silencing across the X chromosomePublished in Cell on Thursday, November 4, 2021
- Identification of neural oscillations and epileptiform changes in human brain organoidsPublished in Nature Neuroscience on Monday, August 23, 2021
- Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and compositionPublished in Nature Medicine on Thursday, May 6, 2021
- Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and FatesPublished in Cell on Tuesday, December 29, 2020
- Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair responsePublished in Cell Stem Cell on Tuesday, November 17, 2020
- A protein assembly mediates Xist localization and gene silencingPublished in Nature on Wednesday, September 9, 2020
- A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem CellsPublished in Cell Stem Cell on Monday, May 11, 2020
- Promoter-Enhancer Communication Occurs Primarily within Insulated NeighborhoodsPublished in Molecular Cell on Thursday, January 17, 2019
- X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCsPublished in Stem Cell Reports on Thursday, April 19, 2018
- Analysis of cardiomyocyte clonal expansion during mouse heart development and injuryPublished in Nature Communications on Wednesday, February 21, 2018
- Cooperative Binding of Transcription Factors Orchestrates ReprogrammingPublished in Cell on Thursday, January 19, 2017
- Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X InactivationPublished in Cell Stem Cell on Thursday, December 15, 2016
- Human Embryonic Stem Cells Do Not Change Their X Inactivation Status during DifferentiationPublished in Cell Reports on Thursday, December 15, 2016
- Glycolytic Metabolism Plays a Functional Role in Regulating Human Pluripotent Stem Cell StatePublished in Cell Stem Cell on Thursday, September 8, 2016
- Naive Human Pluripotent Cells Feature a Methylation Landscape Devoid of Blastocyst or Germline MemoryPublished in Cell Stem Cell on Thursday, February 4, 2016
- X Chromosome Reactivation Dynamics Reveal Stages of Reprogramming to PluripotencyPublished in Cell on Thursday, December 18, 2014
- X Chromosome Reactivation Dynamics Reveal Stages of Reprogramming to PluripotencyPublished in Cell on Thursday, December 18, 2014
- Characterization and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Cardiovascular Progenitor CellsPublished in PLOS One on Tuesday, October 9, 2012
- From skin biopsy to neurons through a pluripotent intermediate under good manufacturing practice protocolsPublished in Stem Cells Translational Medicine on Wednesday, December 7, 2011
- Derivation of new human embryonic stem cell lines reveals rapid epigenetic progression in vitro that can be prevented by chemical modification of chromatinPublished in Human Molecular Genetics on Friday, November 4, 2011
- Mechanistic insights into reprogramming to induced pluripotencyPublished in Journal of Cellular Physiology on Tuesday, January 25, 2011
- Female human iPSCs retain an inactive X chromosomePublished in Cell Stem Cell on Friday, September 3, 2010
- Molecular analyses of human induced pluripotent stem cells and embryonic stem cellsPublished in Cell Stem Cell on Friday, August 6, 2010
- Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression SignaturesPublished in Cell Stem Cell on Thursday, July 2, 2009
- Directed Differentiation of Human‐Induced Pluripotent Stem Cells Generates Active Motor NeuronsPublished in Stem Cells on Monday, February 23, 2009
- Reprogrammed Mouse Fibroblasts Differentiate into Cells of the Cardiovascular and Hematopoietic LineagesPublished in Stem Cells on Thursday, May 1, 2008
- Generation of human induced pluripotent stem cells from dermal fibroblastsPublished in PNAS on Tuesday, February 26, 2008
- Directly Reprogrammed Fibroblasts Show Global Epigenetic Remodeling and Widespread Tissue ContributionPublished in Cell Stem Cell on Wednesday, June 6, 2007
Honors & Affiliations
Honors
- Faculty Scholar Award, Howard Hughes Medical Institute, 2016
- Alexander von Humboldt Professor, Germany, 2014
- John H. Walsh Young Investigator Research Prize, UCLA David Geffen School of Medicine, 2009
Affiliations
- Editorial board, Cloning and Stem Cells, Cell Research, Cell, EMBO Reports, Cell Reports, eLife, Stem Cell Reports, Cell Stem Cell, Development
- Board of Reviewing Editors, Science
- Scientific Advisory Board, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine of Albert Einstein College of Medicine
- International Affairs Committee; Chair, Publication Committee, International Society for Stem Cell Research
- Scientific Advisory Board, Ontario-wide Stem Cell initiative and the Centre for Commercialization in Regenerative Medicine, Toronto, Canada
- UCLA Clinical and Translational Science Institute
- UCLA Molecular Biology Institute
Funding
Plath's work is funded by the National Institute of General Medical Sciences, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and a Faculty Scholar award from the Howard Hughes Medical Institute.