Patricia Maness PhD, Professor
Our research has illuminated a novel principle of selective pruning of dendritic spines in cortical pyramidal neurons mediated by neural cell adhesion molecules (NrCAM, CHOL, L1) and secreted repellent ligands (Semaphorin). Selective spine pruning is essential for sculpting cortical circuits important for working memory and sociability in the prefrontal cortex during the juvenile to adult transition. A consensus site in the cytoplasmic domain of neural adhesion molecules reversibly binds Ankyrin B, an actin adaptor encoded by the high-confidence autism gene Ank2. Some of the mutations in Ank2 associated with autism are within the binding domain of neural adhesion molecules and are likely to disrupt function. We have developed a novel pyramidal cell-specific, inducible Nex1Cre-ERT2: Ank2 mouse line that will be used to probe the molecular mechanism of Ankyrin B in Semaphorin-induced spine pruning and defects associated with its pathological mutations. Validation of this mouse model with assistance from the SOM COVID-19 supplemental award will enable us to define the role of Ankyrin B in development of mammalian circuits.
Silvia B. Ramos MD PhD, Associate Professor
Our research is focused on RNA-binding proteins and their physiopathological roles in vivo. We study RNA-binding proteins using genetically-engineered mouse models to identify novel mRNA targets for RNA-binding proteins and better understand mechanistically how RNA binding proteins are involved in pathological condition. Our focus is an RNA-binding protein that is significantly expressed in many organs, zinc finger protein 36 like 2 (ZFP36L2). This protein destabilizes transcripts containing adenine-uridine rich elements (AREs) located at the 3’ untranslated region of these mRNAs. We have unveiled the role of ZFP36L2 in early embryo development, infertility and in T cells. Our investigation of ZFP36L2’s crucial role in distinct physiological contexts has revealed that overlap between ZFP36L2-target-mRNAs in different tissues is minimal, suggesting that ZFP36L2-targeting is highly tissue specific. To identify factors governing this tissue specificity, we developed a novel Zfp36l2 flox global knockout mouse model (L2-fKO). We are grateful to obtain this SOM COVID-19 supplemental funding which will assist our current ongoing investigation of ZFP36L2 targeting specificity to other organs. Understanding how ZFP36L2 functions at a broader level has naturally developed by the fact that UNC is a hub for RNA biochemistry fostering internal and outside collaborations.
Visit the UNC at Chapel Hill School of Medicine Office of Research for additional COVID-19 funding opportunities.