My lab has had a long-standing interest in JNKs (c-Jun N-terminal Kinases), kinases traditionally characterized as a pro-apoptotic enzyme and necessary for many therapeutic drugs to induce cell death. Recent studies have demonstrated that JNKs can also be activated by growth factors to enhance cell migration and survival. Because of these opposing properties, jnk1 and jnk2 knockout mice have been instrumental in addressing if these properties may be isoform specific. Studies thus far have shown that jnk1 and jnk2 gene products convey diverse functions in various diseases such as diabetes, leukemia and skin cancer research. We are currently evaluating jnk1 and jnk2 function in normal mammary gland development and in mammary tumorigenesis/metastases and response to chemotherapy treatment. We use a wide variety of techniques to evaluate mammary tumor cell biology and mammary gland function. Common methods include transgenic and knockout mouse models and cell lines, organotypic (3D) cell culture, flow cytometry, protein analysis, fluorescent microscopy, gene transfection and gene knockdown approaches to determine the functions of various signaling molecules. These techniques are used to evaluate phenotypes including progenitor/stem cell differentiation, tumorigenesis, metastasis, cellular migration, cancer cell invasion, proliferation, and death.

c-Jun N-terminal Kinase 2 Regulates Multiple Receptor Tyrosine Kinase Pathways in Mouse Mammary Tumor Growth and Metastasis (2011) Genes & Cancer 2, 31-45.

Development of JNK2-Selective Peptide Inhibitors That Inhibit Breast Cancer Cell Migration. (2011) ACS Chem Biol., In press.

c-Jun N-terminal kinase 2 (JNK2) enhances cell migration through epidermal growth factor substrate 8 (EPS8). (2011) Journal of Biological Chemistry 286, 15287-97.

Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model. (2010) PloS ONE 5, e10443.

Stress and IGF-I differentially control cell fate through mammalian target of rapamycin (mTOR) and retinoblastoma protein (pRB). (2008) Journal Of Biological Chemistry 283, 28265-73.

mTOR and PKCd interact to regulate stress and ligand mediated phosphorylation of IRS-1 Ser312 in breast cancer cells (2005) Breast Cancer Research and Treatment 91, 259-269.

Inhibition of JNK reduces G2/M transit independent of p53, leading to endoreduplication, decreased proliferation and apoptosis in breast cancer cells (2004) Oncogene 23, 596-604.

An inhibitory function for JNK in the regulation of IGF-I signaling in breast cancer (2003) Oncogene 22, 602-614.

UV induced apoptosis is mediated independent of caspase-9 in MCF-7 cells – a model for cytochrome C resistance (2003) Journal of Biological Chemistry 278, 45793-45800.

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