LMP student seminars: 4 February
Each week during term time, MSc and PhD candidates in the Department of Laboratory Medicine and Pathobiology present their research.
Anyone is welcome. No need to register.
Location: Medical Sciences Building, rooms 4171 or 4279, see below.
As part of the core research curriculum, students taking LMP1001/2/3: Graduate Seminars in Laboratory Medicine and Pathobiology will present their projects. Please see abstracts below.
Group 2: Cancer, Development and Aging
Location: MSB 4171
Ben Laxer
- Title: Exploring the Developmental Origins of Pediatric Diffuse Midline Glioma Using scRNA Analysis and a Novel Transgenic Zebrafish Model
- Supervisor: Dr. Cynthia Hawkins
Group 1: Brain and Neuroscience
Location: MSB 4279
Jiaqi Li
- Title: Uncovering transcriptional regulators and post-translational processing of LRIG1 in neural stem cells
- Supervisor: Dr. Scott Yuzwa
Abstracts
Ben Laxer: Exploring the Developmental Origins of Pediatric Diffuse Midline Glioma Using scRNA Analysis and a Novel Transgenic Zebrafish Model
Diffuse midline glioma (DMG), H3 K27–altered, is a highly aggressive pediatric brain tumour that arises in midline structures of the brain, most frequently the pons, and carries a median survival of less than one year. Although the H3K27M histone mutation is a defining feature of DMG, this alteration alone is insufficient to drive malignant transformation, indicating that additional developmental or microenvironmental factors may contribute to disease initiation. DMG is diagnosed during early childhood, a period marked by rapid growth and myelination of the pons, suggesting a potential link between normal neurodevelopment and tumour susceptibility.
In this study, I explore the hypothesis that DMG formation depends on the combination of H3K27M-driven epigenetic dysregulation and the unique developmental context of the pons. Preliminary analysis of human scRNA-seq data suggests that neuron–oligodendrocyte interactions may be associated with disease-relevant gene expression programs. These observations raise the possibility that neuronal context and glial developmental state influence vulnerability to transformation during hindbrain maturation.
To further examine the early effects of H3K27M on central nervous system development, I generated a GFAP-Cre–driven H3K27M transgenic zebrafish line, enabling early expression of the mutation in radial glia and downstream glial lineages. Initial characterization confirms expression of H3K27M and reveals developmental timing–dependent changes in gene expression, highlighting candidate pathways that may be relevant to DMG onset.
Together, this work provides novel insight into the developmental mechanisms underlying DMG formation and may inform future efforts toward earlier diagnosis and intervention.
Jiaqi Li: Uncovering transcriptional regulators and post-translational processing of LRIG1 in neural stem cells
Adult neural stem cells (aNSCs) in the mammalian brain are maintained by a precise balance between quiescence and activation, regulated by niche-derived signals and intrinsic transcriptional programs. LRIG1 (Leucine-rich repeats and immunoglobulin-like domains protein 1) is a transmembrane protein implicated in the regulation of receptor signaling; however, the mechanisms controlling its expression and molecular processing in the adult neural stem cell niche remain poorly understood. Here, using ex vivo brain slice cultures, we investigate both the transcriptional and post-translational regulation of endogenous LRIG1.
Pharmacological perturbation of epigenetic regulators, including inhibition of the histone acetyltransferase p300 and DNA methylation modulation by 5-azacytidine, reveals that LRIG1 expression is under epigenetic transcriptional control. At the protein level, LRIG1 is detected as two distinct molecular species, indicating regulated post-translational processing. The relative abundance of these LRIG1 forms is sensitive to calcium levels and protease inhibition, supporting a model in which LRIG1 undergoes regulated proteolytic cleavage in the neural stem cell niche.
Functionally, alterations in LRIG1 processing are associated with changes in SMAD1 signaling, suggesting that LRIG1 cleavage may modulate BMP pathway activity, a central regulator of aNSC quiescence and activation. Together, these findings identify LRIG1 as a dynamically regulated protein controlled at both transcriptional and post-translational levels, and reveal regulated processing of LRIG1 as a potential mechanism for fine-tuning niche signaling in adult neural stem cells.
Contact
No need to register.
Contact lmp.grad@utoronto.ca with any questions.