Amy H. Bouton, PhD

Amy H. Bouton, PhD

Amy  H.  Bouton
Degree(s): PhD
Graduate School: University of Virginia
Primary Appointment: Professor, Microbiology, Immunology, and Cancer Biology
Research Interests:
Signaling Pathways that Regulate Tumor Growth, Metastasis, and Response to Anticancer Agents; Adhesion Signaling In Macrophages; Bacteria-Host Cell Interactions
Email Address:

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), which are an important immunological component of the tumor microenvironment, have been shown to promote the growth and metastatic spread of breast tumor cells.  However, the mechanisms through which TAMs communicate with tumor cells to promote tumor growth and metastasis are not clear.

We have been testing the hypothesis that FAK may contribute to the tumor-promoting activity of TAMs with the use of a myeloid-specific conditional FAK knockout mouse, in which FAK is genetically deleted from cells of the myeloid lineage (including macrophages).  These studies address a pressing need in the field of tumor biology to understand the molecular and cellular mechanisms that underlie the communication between macrophages that function within the tumor microenvironment and the tumor cells themselves.  They also provide the experimental underpinning for designing therapeutic strategies that combine drugs that target tumor cells with drugs that target the supporting cells of the microenvironment that contribute to tumor growth and metastasis.  In fact, small molecule inhibitors of FAK have recently been identified that exhibit significant anti-tumor effects in preclinical models and Phase I clinical trials.  The mouse model that we are developing will allow us to gain a better understanding of how these drugs might be used in combination with other cancer therapeutics to control tumor growth and metastasis.

Selected Publications

Ray BJ, Thomas K, Huang CS, Gutknecht MF, Botchwey EA, Bouton AH.  Regulation of osteoclast structure and function by FAK family kinases. J Leukoc Biol. 2012 Nov;92(5):1021-8. doi: 10.1189/jlb.0512259. Epub 2012 Aug 31.

Guerrero MS, Parsons JT, Bouton AH.  Cas and NEDD9 Contribute to Tumor Progression through Dynamic Regulation of the Cytoskeleton. Genes Cancer. 2012 May;3(5-6):371-81. doi: 10.1177/1947601912458585.

Stokes JB, Adair SJ, Slack-Davis JK, Walters DM, Tilghman RW, Hershey ED, Lowrey B, Thomas KS, Bouton AH, Hwang RF, Stelow EB, Parsons JT, Bauer TW.  Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011 Nov;10(11):2135-45. doi: 10.1158/1535-7163.MCT-11-0261. Epub 2011 Sep 8.

Abshire MY, Thomas KS, Owen KA, Bouton AH.  Macrophage motility requires distinct α5β1/FAK and α4β1/paxillin signaling events. J Leukoc Biol. 2011 Feb;89(2):251-7. doi: 10.1189/jlb.0710395. Epub 2010 Nov 17.

Owen KA, Abshire MY, Tilghman RW, Casanova JE, Bouton AH.  FAK regulates intestinal epithelial cell survival and proliferation during mucosal wound healing. PLoS One. 2011;6(8):e23123. doi: 10.1371/journal.pone.0023123. Epub 2011 Aug 24.

PubMed Listings for this Faculty Member

Contact Information
Office Address: PO Box 800734, Jordan Hall, Room 7045
Office Phone: 434-924-2513, 434-924-9995
Fax Phone: 434-982-1071