Structural & Cellular Biology

Associate Professor
Vice-Chair for Research
Piltz Professor for Cancer Research

browan@tulane.edu

Research Interests:

Nuclear Receptor Phosphorylation in Breast Cancer: The major focus of our research program is on mechanisms by which phosphorylation of estrogen receptor and coregulators impacts standard of care therapy for breast cancer. The goal is rational design of combination therapeutics with agents directed at kinases/phosphatases. Ongoing studies identify phosphorylation fingerprints for estrogen receptor and coregulators that are associated with gene-specific transcription and breast cancer growth. The laboratory also identifies novel phosphorylation sites in nuclear receptors and develops phosphorylation site specific antibodies that are used for laboratory studies and as predictive factors for breast cancer. As part of this direction, experiments quantitate active kinase expression in patient biopsies during progression from normal to malignant cancer. A translational project is evaluating preclinical efficacy of a novel clinical src kinase inhibitor, KXO1, in combination with endocrine therapy and chemotherapy.

Adipocyte stem cells in reconstructive surgery and soft tissue repair: Adipocyte stem cells (ASCs) are present in adipose tissue and serve as precursors for mature adipocytes. ASCs are used in various applications of regenerative medicine and soft tissue repair. In collaboration with Drs. Ernest Chiu, Paul Friedlander and Jeffrey Gimble, our research group is evaluating the use of ASCs in reconstructive surgery for breast and head/neck cancer patients.

Metastatic Breast Tumor Model developed from Patient Biopsies: Metastatic breast cancer is the leading cause of death in breast cancer patients independent of the manageability of the primary disease.  The study of breast cancer has depended heavily upon the use of established breast cancer cell lines, whose origin is often from pleural effusions or metastatic lesions.  Hetero-transplantation of primary tumor biopsies from patients into immunodeficient mice has many advantages over standard xenografts from cancer cell lines.  The hetero-transplant tumors can be directly compared to the original patient tumor biopsies, and to annotated information on patient features, family history, patient outcome etc. The tumors more closely resemble the genetic phenotype of the patient which has important implications for testing response to therapeutics. Unfortunately, only a very small percentage of human breast tumor tissue directly transplanted into immunodeficient mice results in tumor formation.  We developed reproducible, hetero-transplant breast tumor model derived from primary needle biopsies from patients diagnosed with primary invasive ductal carcinoma. The method involves in vitro selection for non-adherent mammospheres that are subsequently transplanted into mice and exhibit a highly metastatic phenotype. Current studies compare the molecular phenotype of tumors at the primary and metastatic sites, and use the model to test novel therapeutics for metastatic disease.

Representative Publications:

Dong C, Yuan L, Dai J, Lai L, Mao L, Xiang S, Rowan B, Hill SM. (2010). Melatonin inhibits mitogenic cross-talk between retinoic acid-related orphan receptor alpha (RORalpha) and ERalpha in MCF-7 human breast cancer cells. Steroids, June 15 [Epub ahead of print].

Georgios Skliris, Zoann Nugent, Brian G. Rowan, Carla Penner, Peter Watson, Leigh Murphy (2010). A phosphorylation code for oestrogen receptor alpha predicts clinical outcome to endocrine therapy in breast cancer Endocrine Related Cancer 17(3):589-97

Ramayya, M., Sheng, M., Xiang, S., Hill, S.M., Rowan, B.G. (2010). Human Steroidogenic Factor-1 Suppresses Proliferation of Human Ovarian Surface Epithelial Cancer Cell. Journal of Steroid Biochemistry and Molecular Biology 119(1-2):14-25.

Williams, C., Basu, A, El-Gharbawy, A., Carrier, L., Smith, C.L., Rowan, B.G. (2009). Identification of Four Novel Phosphorylation Sites in Estrogen Receptor alpha: Impact on Receptor-Dependent Gene Expression and Phosphorylation by Protein Kinase CK2. BMC Biochemistry 10(1):36.

Carolyn G. Marsden, Mary Jo Wright, Radhika, Pochampally and Brian G. Rowan. (2009). Breast tumor-initiating cells isolated from patient core biopsies for study of hormone action. Methods Mol Biol. 590:363-75.

Zengshan Li, Latonya Carrier, Aditi Belame, Aruntha Varani Thiyagarajah, Virgilo A. Salvo, Matthew Burow, Brian G. Rowan. (2009) Combination of selenium with tamoxifen inhibits MCF-7 breast cancer xenografts in nude mice through elevated apoptosis and reduced angiogenesis Breast Cancer Research and Treatment, 118(1):33-43.

Al-Dhaheri, M. and Rowan, B.G. (2007) PKA exhibits selective modulation of estradiol dependent transcription in breast cancer cells that is associated with decreased ligand binding, altered ERα promoter interaction and changes in receptor phosphorylation. Molecular Endocrinology, 21(2):439-56.

Shah, Y and Rowan, B.G. (2005). The Src Kinase Pathway Promotes Tamoxifen Agonist Action through Phosphorylation-Dependent Stabilization of Estrogen Receptor a Promoter Interaction and Elevated SRC-1 Activity. Molecular Endocrinology, 19(3):732-48.

Desouki, M.M. and Rowan. B.G. (2004). Src Kinase and MAP Kinases in the Progression from Normal to Malignant Endometrium. Clinical Cancer Research, 10(2):546-55.