John Foley Lab

Research Interests

The Foley lab: Growth factor signaling in cancer, skin and bone.

 An emerging understanding of the pathology of cancer suggests that the progression of tumors results from the ability of cancer cells to manipulate the normal cells in their immediate environment and to some extent the entire body. This involves a series of complex interactions with blood vessels, the immune system, connective tissue and specialized cells of certain organs.  These interactions are required to sustain tumor cell growth and also result in destruction of the organ the neoplasm grows within.  The basis of these interactions is the exchange of growth factors between tumor cells and normal cell types.  My lab is focused on parathyroid hormone-related protein (PTHrP), which was first identified due to its association with the paraneoplastic syndrome humoral hypercalcemia.  In this syndrome, high levels of tumor-derived PTHrP enter the circulation, activate the PTH receptor in bone and kidney cells, resulting in resorption of bone and kidney dysfunction.  It is now clear that PTHrP is made by a wide variety epithelial cell derived tumors that do not produce humoral hypercalcemia of malignancy.  It plays a central role in tumor cell metastasis to bone and is likely to influence tumor- normal cell interactions that precede metastasis.  Current efforts in the lab involve identifying the signaling events that activate PTHrP gene expression in tumor cells. Recently, we have found that epidermal growth factor receptor (EGFR) and its ligands appear to be the primary activator of PTHrP gene expression in normal epidermal keratinocytes as well as lung and breast cancer cells.  We have used this observation to begin testing EGFR targeted therapeutics in animal models of humoral hypercalcemia of malignancy.   We are also using these therapeutics in animal models of breast cancer metastasis to bone.  These studies are leading to revised understanding of how the receptor signals, a novel application for the EGFR inhibitors in cancers and the creation of screening tools that will identify improved therapeutics that for this growth factor pathway. 

In addition this research is providing insights into how these two signaling pathways intersect in basic bone endocrinology and skin biology.  Currently we are investigating how sex steroid hormones influence the development and physiology of the specialized skin of the nipple and how this structure changes to undertake the major role in milk delivery. We also are exploring how the EGFR and PTHrP pathways coordinate epidermal, dermal, vascular and immune responses to sunburn with a long term goal of determining whether this impacts bone health.

Recent publications:

Cho, Y-M., Lewis D. A., Koltz P. F., Richard V., Rosol T. J., Konger R. L., Spandau D.F. Foley J. (2004) Regulation of Parathyroid Hormone-related Protein gene expression by EGF family ligands in primary human keratinocytes Journal of Endocrinology 181: 179-190

Richard V., Rosol T.J. Foley J. (2005) PTHrP gene expression in cancer: do all paths lead to Ets? Critical Reviews in Eukaryotic Gene Expression. 15:115-32,

Diamond AG, Gonterman RM, Anderson A, Menon K, Offutt CD, Weaver C, Philbrick WM and Foley J.  (2006) Parathyroid hormone related-protein and the PTH receptor regulate angiogenesis of the skin. Journal of Investigative Dermatology 126:2127-34

Eastwood J, Offutt CD, Menon K, Keel M  Hrncirova P, Novotny MV, Arnold R and Foley J. (2006) Identification of markers for nipple epidermis: changes during pregnancy and lactation. Differentiation 74: 1-9

Widelitz, RB Veltmaat J, Mayer J Foley, J and Chuong C-M (2007) Mammary glands and feathers: Comparing two skin appendages which help define novel classes during vertebrate evolution Seminars in Cell and Developmental Biology.