The cellular innate immune response to viruses is a defense mechanism executed by most cells in the human body to form the initial barrier to virus replication. Detection of viral nucleic acids initiates widespread gene expression changes that combine to establish an antiviral state and stimulate professional immune cell activation....
Proper size control of organs and tissues is critical to their function, and it is necessary for the millions of precisely sized tubes that make up those organs— for example, excessive cell growth can lead to devastating diseases such as Polycystic Kidney Disease. The regulation of tube growth is therefore...
Neural crest cells are a population of multipotent stem cells that are unique to vertebrates and give rise to a wide range of derivatives in the developing embryo, including elements of the craniofacial skeleton, pigmentation of the skin and peripheral nervous system. Although these cells reside in the ectoderm, they...
Splicing factor 3B1 (SF3B1) is a core splicing protein that stabilizes the interaction between the U2 snRNA and the branch point (BP) in the RNA target during splicing. SF3B1 is heavily phosphorylated at its N terminus and a substrate of cyclin-dependent kinases (CDKs). Although SF3B1 phosphorylation coincides with splicing catalysis,...
Many transcription factors (TFs) regulate oncogenic processes and are therefore desirable targets for drug intervention. However, few TF inhibitors have been developed to date due to a lack of specificity and few TF binding pockets. The Meade Lab has overcome these challenges by using cobalt-based complexes that disrupt Cys2His2 zinc...
Epigenetics is the study of chromatin-based events that regulate gene expression without the change of DNA sequence, including DNA methylation, histone modification and chromatin remodeling. Epigenetic regulators are encoded to modify chromatin in a highly regulated and dynamic manner. A growing number of studies have suggested the dysregulation of epigenetic...
RNA repair pathways exist in all three domains of life. In eukaryotes, they play key roles in fundamental biological processes such as tRNA splicing and endoplasmic reticulum (ER) stress induced noncanonical splicing of a master transcription factor mRNA (named XBP1 in mammalian cells). Even though most living organisms contain an...
The apolipoprotein E (APOE) E4 isoform is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). While APOE is predominantly expressed by astrocytes in the central nervous system, neuronal expression of APOE is of increasing interest in age-related cognitive impairment, neurological injury, and neurodegeneration. Here we show that endogenous...
The blueprint of life is contained within the sequence of an organism’s genome. While virtually all cells of an individual multicellular eukaryotic organism contain a near identical code of nucleic acid sequences, an organism must give rise to and maintain a varied set of cells and phenotypes. As such, sequence...
Promyelocytic leukemia (PML) nuclear bodies act as quality control centers in the nucleus, participating in a plethora of nuclear functions. As such, PML bodies are a signature model for functional nuclear organization. PML bodies have a dynamic protein composition that responds to changing conditions of the cell. Many of the...