The Vasudevan Lab studies growth factor signaling during development and cancer with an emphasis on neurofibromatosis and an eye toward technology development. We are currently interested in a number of different cancers including peripheral nervous system tumors (such as neurofibromas, schwannomas, and MPNSTs), central nervous system tumors (such as glioma and glioblastoma), and metastatic nervous system tumors (with a focus on melanoma). 

Neurofibromatosis: The cancer predisposition syndrome neurofibromatosis type I (NF1) is caused by loss of the neurofibromin tumor suppressor gene, a GAP that negatively regulates Ras signaling and serves as a key downstream effector of RTKs. Patients with NF1 are at increased risk for developing many nervous system tumors, including Schwann cell derived neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). To personalize treatment for these patients, we have defined predictive and prognostic signatures in MPNSTs. Our more recent work focuses on how Schwann cell differentiation underlies malignant transformation and treatment resistance to MEK inhibitors, the only FDA approved therapy for neurofibromas arising in patients with NF1, identifying a functional relationship between the NF1 and NF2 tumor suppressors. Ongoing projects are investigating the transformation of neurofibroma to MPNSTs and identifying druggable dependencies of NF1 associated cancers. 

Genomic analysis of nervous system tumors: Understanding the molecular correlates of tumorigenesis requires integration of multiple bulk and single cell genomic modalities including DNA methylation profiling, whole exome sequencing (WES), and RNA-sequencing (RNA-seq). I have previously applied such an integrative approach to meningiomas, the most common primary CNS tumor in the United States, and ependymoma, both of which are associated with neurofibromatosis. Ongoing projects focus on the molecular landscape of NF1 associated tumors, (melanoma) brain metastases and applying novel single cell technologies to better define the heterogeneity within these tumors.

Growth factor signaling through receptor tyrosine kinases (RTKs) and the Ras signaling pathway: The mechanisms through which receptor tyrosine kinases specify distinct cellular outcomes despite signaling through a shared set of intracellular pathways is a fundamental question in signal transduction. RTK signaling is required for development of the embryonic neural crest, and in numerous cancers arising from this lineage including schwannomas, neurofibromas, and melanomas. Ongoing projects in the lab are investigating how to modulate oncogenic RTK signaling and identifying novel regulatory mechanisms linking RTKs to NF1 and the Ras signaling pathway.

Technology development: Scientific advancement requires the incorporation of novel and robust technical approaches to uncover critical insights. As our interest in tumor heterogeneity necessitated the ability to connect DNA genotype to protein phenotype, we developed a novel pipeline combining targeted single cell DNA sequencing with antibody-sequencing to measure surface protein expression, a technology termed DNA-Antibody sequencing (DAb-seq) that permits joint genotype-phenotype identification in single cells. Ongoing projects focus on developing and applying novel single cell approaches to better understand tumorigenesis, classify cancer types, and monitor responses to therapy.