GRAD STUDENTS

HUI LI

Gavis Lab

Understanding the roles of Drosophila Fragile X mental retardation protein (dFMRP) in regulating dendrite patterning

Dendritic arbor development is a complex and highly regulated process. Post-transcriptional regulation mediated by RNA-binding proteins (RBPs) plays an important role in neuronal dendrite morphogenesis by delivering on-site, on-demand protein synthesis. The Fragile X mental retardation protein (FMRP), a highly conserved RNA-binding protein, has been implicated in neuronal development as a post-transcriptional regulator. Here, using class IV da neurons, a group of highly branched Drosophila larval sensory neurons, we uncover critical roles for dFMRP in cytoskeleton-dependent dendrite growth. In addition, since Fragile X Syndrome (FXS) caused by loss of functional FMRP was previously linked to miRNA pathway dysfunction in spine maturation and axon elongation, we are also investigating whether and how dFMRP regulates dendritic patterning through miRNA pathway. Our studies reveal a primary role of dFMRP in dendrite branching morphogenesis, and may also shed light on the miRNA-dependent dendrite developmental pathology of FXS.

NOEL PARK

Rabinowitz Lab

Probing metabolic heterogeneity of germinal center B cells in vivo

There is a clear link between immune cell metabolism and function. Mounting an effective humoral response requires precise regulation of B cells as they transition through different cell states and microenvironments. Upon an antigenic encounter, transient and dynamic microstructures of B cells called germinal centers form within B cell follicles in secondary lymphoid tissues, such as the spleen. Germinal center B cells are the most rapidly proliferating non-cancerous cells in the body. Currently, there is a dearth of metabolic studies of germinal center B cells in vivo due to technological limitations. To address this challenge, we have developed a multimodal pipeline coupling stable-isotope infusions and imaging mass-spectrometry to explore the spatial metabolic landscape of splenic B cells in response to immunization in mouse. Additionally, we carried out orthogonal measurements using LCMS. By harnessing the two techniques, we show for the first time that germinal center B cells preferentially utilize glucose for the TCA cycle in vivo, going against the in vitro data in literature. Future work in plan includes investigating malignantly transformed B cells and their metabolic vulnerabilities, and modulating whole-body metabolism for improving immune response.