Bouton, Amy H.

Amy Bouton

Amy H. Bouton

Primary Appointment

Professor and Associate Dean for Graduate and Medical Scientist Programs, Microbiology, Immunology, and Cancer Biology

Education

  • ScB, Biology, Brown University
  • PhD, Microbiology, University of Virginia
  • Postdoc, Signal Transduction, University of Virginia

Contact Information


Telephone: 434-924-2513
Email: ahb8y@virginia.edu

Research Interests

Signaling Pathways and Breast Cancer

Research Description

The survival of organisms ranging from simple bacteria to complex metazoans relies on the ability of individual cells to sample the environment and respond appropriately. Understanding the molecular pathways involved in these responses is of fundamental importance for many areas of biomedical science including cancer biology and microbial pathogenesis, both of which are major research foci of our lab. A short description of our work in each of these areas is presented below. One of the major research areas in our lab focuses on determining molecular mechanisms by which breast cancer cells become resistant to the growth-inhibitory effects of a class of compounds called antiestrogens (competitive inhibitors of the estrogen receptor). This is a significant problem in breast cancer treatment, since approximately 50% of breast tumors never respond to antiestrogen therapy, and the majority of tumors that initially respond acquire resistance to these drugs over time. We have been investigating the biological activities of two proteins, Cas and BCAR3, which have been shown to confer resistance of breast cancer cells in culture to antiestrogens such as tamoxifen. Interestingly, human breast tumors that overexpress Cas are significantly less likely to respond to first-line tamoxifen therapy, and the prognosis of patients with these tumors is poor. We hypothesize that one of the effects of high Cas and BCAR3 expression is activation of signaling pathways that allow breast cancer cells that are usually dependent on estrogens for growth to proliferate in the absence of estrogens. We are currently testing aspects of this hypothesis using both tissue culture and mouse models of breast cancer with the goal of 1) better predicting whether a particular tumor is likely to fail antiestrogen therapy so that other treatment approaches can be initiated more quickly, and 2) rendering previously resistant tumors sensitive to tamoxifen treatment by blocking Cas- or BCAR3-specific functions. Our research program also studies adhesion signaling in macrophages. As a key component of the innate immune system, macrophages play a central role during tissue remodeling and following injury or infection. Because of their broad functions and heterogeneous character, these cells are extremely responsive to environmental cues that signal the need for differentiation and maturation, activation, migration and invasion, and/or phagocytosis. Two protein tyrosine kinases, focal adhesion kinase (FAK) and its close relative Pyk2, function as regulators of many of these biological processes. Using both mouse models and primary bone marrow macrophages, we have been investigating how FAK and Pyk2 regulate macrophage adhesion, migration, infiltration into sites of inflammation, and phagocytosis of the bacterial pathogen Yersinia pseudotuberculosis. In addition to our work on basic macrophage cell biology and innate immunity, we have been studying how FAK expression in macrophages contributes to breast and melanoma tumor growth and metastasis. In recent years, it has become clear that tumor progression and metastasis are not only governed by the genetic properties of tumor cells, but also by interactions between the tumor cells and a large assortment of host" cells that make up the "tumor microenvironment." Tumor-associated macrophages (TAMs)

Selected Publications