- Assistant Research Molecular Biologist
- Principal Investigator, Meningioma Research Laboratory
- CoInvestigator: Michael McDermott MD
Current Research Project
Dr. Lal's laboratory uses serial analysis of gene expression (SAGE) to define the transcriptome of meningiomas. The SAGE technology has proven useful for this purpose because of its ability to evaluate the expression pattern of thousands of genes in a quantitative manner without any prior sequence information. Preliminary data have allowed her group to identify a large number of genes and some genetic pathways that are altered in higher-grade meningiomas including several cell cycle and apoptosis regulators. A detailed characterization will allow them to differentiate between the genes that actually contribute to meningioma pathogenesis from those that simply reflect a cancerous phenotype.
Of particular interest to Dr. Lal are implications that the Notch signaling pathway and the Groucho/TLE corepressors contribute to the malignant progression of meningiomas. Preliminary studies done her her laboratory reveal deregulated expression of the Notch signaling pathway in meningiomas of all three malignancy grades, and inducement of Gro/TLE corepressors in higher-grade meningiomas. Gro/TLE corepressors interact with and modulate the activity of a wide range of transcriptional regulatory systems, one of which is HES1. Her group is currently investigating the prognostic significance and the mechanism of deregulation of the Notch pathway in meningiomas, and is evaluating the therapeutic potential of inhibitors of the Notch pathway.
Crucial to understanding the role of individual genes in meningioma pathogenesis is the availability of tumor model systems that recapitulate essential features of the human disease. Meningioma model systems are rare and most studies have relied on using primary cultures of meningiomas, which have limited utility. The second focus of Dr. Lal's laboratory is to develop in vitro and in vivo meningioma model systems from bulk meningioma tissue and to develop a genetic model of meningiomas using primary cultures of arachnoidal cells, the presumed cell of origin for meningiomas.