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The laboratory of Steve Angus, PhD, focuses on the changes in protein kinase signaling network during tumor development and progression.

Angus Lab

The laboratory of Steve Angus, PhD, is interested in understanding the changes in the protein kinase signaling network (the kinome) during tumor development and progression and in response to targeted therapeutics. Dr. Angus' lab has developed a chemical proteomic approach that provides a unique, quantitative portrait of the functional kinome that they integrate with genomic data. The goal of Dr. Angus' lab is to identify kinases that may be especially susceptible to targeted treatment strategies in rare pediatric cancers and other tumor types.

Dr. Angus conducts his research within the Pediatric Molecular Oncology and Experimental Therapeutics Program at the Herman B Wells Center for Pediatric Research.

Herman B Wells Center for Pediatric Research

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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.

Research Funding

  • Ralph W. and Grace M. Showalter Research Trust Award
    Showalter Trust Award (2020-2021)

Recent Publications

  • 2018

    Angus SP, Oblinger JL, Stuhlmiller TJ, et al. EPH receptor signaling as a novel therapeutic target in NF2-deficient meningioma. Neuro Oncol. 2018;20(9):1185-1196. doi:10.1093/neuonc/noy046

    Brighton HE, Angus SP, Bo T, et al. New Mechanisms of Resistance to MEK Inhibitors in Melanoma Revealed by Intravital Imaging. Cancer Res. 2018;78(2):542-557. doi:10.1158/0008-5472.CAN-17-1653

    Angus SP, Zawistowski JS, Johnson GL. Epigenetic Mechanisms Regulating Adaptive Responses to Targeted Kinase Inhibitors in Cancer. Annu Rev Pharmacol Toxicol. 2018;58:209-229. doi:10.1146/annurev-pharmtox-010617-052954

For a full list of Dr. Angus' publications, find him on PubMed.

Faculty Research Team

44779-Angus, Steve

Steve Angus, PhD

Assistant Professor of Pediatrics

Read Bio Steve Angus, PhD

Additional Research Team Members

Additional lab team members include Research Analyst Chris Davis, and Research Technician Shelley Dixon.