Research

The Vasudevan Lab studies growth factor signaling during development and cancer with an emphasis on neurofibromatosis and an eye toward technology development for both diagnostic and therapeutic applications. Ongoing projects in the lab include:

Neurofibromatosis

1. Understanding the mediators of NF1 function

2. Elucidating druggable dependencies of NF1 associated cancers

3. Delineating Ras GAP specificity in development and disease

Cancer genomics and treatment resistance

1. Defining the bulk and single cell molecular landscape of nervous system tumors

2. Determining molecular mediators of resistance to targeted therapy and radiation 

3. Uncovering mechanisms of therepeutic response in primary and metastatic nervous system tumors

Technology development

1. Identifying and characterizing rare cell populations

2. Testing and applying single cell approaches for CNS metastases

3. Developing novel diagnostics for brain tumors

 

Vasudevan et al. Neurosurgery (2021).

 

 

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.

 

 

 

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). 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.

Growth factor signal specficificity through receptor tyrosine kinases (RTKs) and Ras GAP proteins: 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. 

Demaree, Delley, Vasudevan et al. Nature Communications, 2021.

 

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.