1. One of our goals is o better understand the functions of the two forms of the progesterone receptor (PR), PR-A and PR-B. These isoforms have different transcriptional activites and different roles in breast cancer prognosis, tumor growth, and response to treatments, and we have undertaken detailed protein structural analyses of the two receptors focused on the large N-terminal region. To this end the proteins are overexpressed in insect cells, purified to homogeneity, and analyzed by a variety of protein structural and biophysical methods.
2. Studies also include detailed N-terminal mapping studies involving site-specific and random mutagenesis of regions unique to PR-B, and studies addressing the role of post-transcriptional protein modifications, like phosphorylation and SUMOylation, on receptor function.
3. N-terminal binding, transcriptional coregulatory proteins are being identified.

4. We take advantage of the power of expression profiling to define genes involved in estrogen and progesterone signaling, cross-talk between the two receptor systems, tumor metastasis, etc.
5. Inducible human breast cancer cell models have been developed in which receptors are "off" until switched "on". These are used to refine expression analyses, to probe for ligand-independent effects of receptors, and to analyze differential receptor effects on tumor response to hormonal and chemotherapeutic agents including effects of taxanes.

6. Hormones and their roles in breast cancer growth are elucidated with different human breast cancer cell lines with varying estrogen receptor (ER) and/or PR content. These cell lines are grown as hormone-dependent tumors in nude mice and analyzed for the role of receptors and hormonal treatments on tumor growth and regression.
7. Breast cancer metastasis is being studied with powerful new models have been created using highly green and red fluorescent tumor cells that allow accurate tracking of the spread of cells out of primary tumor sites to metastatic sites in the nude mice. Expression profiling and other studies address mechanisms for hormone regulation of metastases.

8. In collaborative studies, the observations and hypotheses derived from basic research studies are extended into translational research using tumors taken from patients.
9. Patient tumor samples are also used to analyze the role of tumor cells in altering the tumor microenvironment and stromal/epithelial cell interactions.