The Vasudevan Lab studies growth factor signaling during development and cancer with an emphasis on neurofibromatosis. Our goal is to develop novel diagnostic and therapeutic strategies to improve the care of all people.
Ongoing projects in the lab include:
Neurofibromatosis and Ras GAP biology:
1. Understanding the mediators of neurofibromatosis tumor suppressor function
2. Elucidating therapeutic vulnerabilities in neurofibromatosis associated cancers
3. Delineating mechanisms of tumor and normal tissue heterogeneity in people with neurofibromatosis
4. Dissecting Ras GAP specificity in development and disease
Nervous system tumor genomics
1. Defining molecular groups and biomarkers of peripheral nerve tumors
2. Determining the molecular classification of NF1 mutant tumors
3. Developing better treatment strategies for both central and peripheral nervous system tumors
Technology development
1. Improving single cell and spatial multi-omic approaches
2. Building better mouse tools to study Ras (GAP) biology in vivo
Neurofibromatosis and Ras GAP Biology: 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.The mechanisms through which Ras (GAP) signaling specifies distinct cellular outcomes despite signaling through a shared set of intracellular pathways is a fundamental question in signal transduction. Moreoever, Ras GAP signaling is required for development of the embryonic neural crest, and in numerous cancers arising from this lineage including schwannomas, neurofibromas, and melanomas.
Nervous system tumor genomics: 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). In addition to our work with schwannomas, neurofibromas, and MPNSTs, we 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, and to melanoma brain metastasis, which are the most common cause of death in patients with melanoma.
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.