Our laboratory belongs to the Department of Biological Chemistry at the School of Medicine of the University of California, Los Angeles. We are also part of the Broad Stem Cell Center and Gene Regulation Group at UCLA.
The Plath lab is a team of molecular and cell biologists that is supported by computational biologists, as we often utilize genomics approaches coupled with biochemistry, molecular biology, cell biology, and functional assays to uncover fundamental principles of how gene expression patterns are altered during cell fate changes. Thus, all projects in our lab employ genomics and computational approaches if it is advantageous to answer our questions.
Plath lab January 2015
Since epigenetic changes can be key to pathological development, we are extending our work on normal cell fate change processes to those occurring in disease states, where we can. We collaborate with other laboratories if the appropriate synergies arise and share a NIH program project grant with the Lowry, Smale, and Zaret labs at UCLA and UPENN to understand barriers of cell fate transitions during differentiation and reprogramming.
Cell and Molecular Biology
Our group uses pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) and transcription factor-induced reprogramming of somatic cells to pluripotency to examine the regulation of X-inactivation, 3D genome organization, gene expression, and chromatin states. We use both human and mouse cells as remarkable differences exist between these two systems. We often employ imaging approaches at the single cell level to understand changes in gene expression programs, chromatin states, and 3D genome organization. Our transgenic and knockout mouse models also allow us to derive cell lines for reprogramming experiments and studies of X-inactivation.
We use various methods to perturb lncRNA and protein coding genes to define their function in X-inactivation, reprogramming, and 3D genome organization, including genome editing approaches such as the CRISPR/Cas system. We are also performing high-throughout screening in collaboration with the Molecular Shared Screening Resource at UCLA to reveal new players.
Through biochemistry in combination with mass spectrometry, we have identified new regulators of X-inactivation and transcriptional control.
Genomics and Computational Biology
We often use large-scale genomics approaches to map the patterns of RNA expression (at the single cell and population level) (RNA-seq), DNAse hypersensitivity (ATAC-seq), DNA methylation (RRBS, MRE, WGBS), histone modifications (ChIP-seq), transcription factor binding, 3D genome organization (Hi-C and 4C-seq), and RNA localization on chromatin (RAP-seq). We run our samples at the high-throughput sequencing core of the UCLA Broad Stem Cell Center. We also develop novel computational tools and methods to integrate large-scale data sets to learn new principles and test hypotheses. Here, we often work with the Ernst and Pellegrini labs at UCLA (see collaborations).