Angus Lab

Active Research

The Angus Lab studies dysregulated signaling networks that are characteristic of cancer and disease. Specifically, we use proteomics and genomics to characterize adaptive responses of tumors to targeted kinase inhibitors.

Kinases propagate cell signaling cascades and regulate key cellular processes including proliferation, survival, invasion, and metastasis. Due to their profound importance, kinases are frequently mutated, over expressed, or otherwise deregulated in cancer and disease. Consequently, over 50 kinase inhibitors are FDA approved and used to treat cancer and autoimmune diseases. While kinase inhibitors have led to remarkable clinical responses, tumors almost invariably become resistant and bypass targeted therapy.

In the Angus Lab, we study the impact of targeted kinase inhibitors on the global kinase signaling network—the functional kinome—using a novel chemical proteomics approach combining multiplexed inhibitor beads and mass spectrometry. We additionally utilize next-generation sequencing to study expression changes, mutations, and copy number changes—all of which can drive therapeutic resistance.

We apply these techniques to mammalian cell culture models, in addition to genetically engineered mouse models, patient-derived xenografts, and clinical samples at baseline, early during treatment, and when drug resistance arises.

We are studying plexiform neurofibroma (PNF), a hallmark tumor of patients with neurofibromatosis type 1 (NF1), progression to malignant peripheral nerve sheath tumors (MPNST), the leading cause of death for NF1 patients. Our goal is to extend mechanistic insights regarding kinase regulatory networks to identify novel biomarkers and therapeutic targets to improve patient response.