Department of Biochemistry
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     Awad. W.
    Barredo,
    Barrientos, T.
    Baumbach, L.
    Carraway, K.
    Elsas, L.
    Howard, G.
    Hu, Jennifer
    King, M.L.
    Neary, J.
    Norenberg, M.
    Schesser, K.
    Schiller, P.
    Slingerland, J.
   
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Calendar		 Joyce Slingerland

Professor of Medicine
Director Braman Breast
Cancer Institute

MD (1988) Univ. of Toronto

 breast cancer, molecular mechanisms, cell cycle,
estrogen receptors.

Research Interest:
Dr. Slingerland’s career in research has been devoted to translation of mechanistic aspects of cell cycle and hormonal regulation of breast cancer. The Slingerland lab investigates how breast cancer cells escape growth control by antiestrogens and inhibitory cytokines. During her post-doctoral work, Dr. Slingerland made the innovative discovery of a key inhibitor of cell cycle progression, p27. Her lab has investigated how p27 is regulated by hormones and mitogenic and growth inhibitory factors in normal and cancer cells. Slingerland et al. demonstrated that p27 levels are reduced in up to 60 % of common human breast and other cancers in association with poor patient prognosis.

Dr. Slingerland showed that the growth arrest by inhibitory cytokines such as TGF-b and antiestrogens in breast cancer requires the cdk inhibitors p21 and p27. She showed that constitutive signaling via Her2 and MAPK activation deregulates p27 function causing Tamoxifen resistance in breast cancer. She and others demonstrated that a major mechanism of breast and other human cancer progression involves loss or inactivation of p27 through increased p27 degradation, its cytoplasmic mislocalization or sequestration in aberrant protein complexes. Ongoing research addresses how signaling via the phospho-inositol 3’kinase (PI3K) and Ras/Src/Raf/MAPK pathway modulates p27 phosphorylation and function. The consequences of pathway activation and specific effectors that modulate p27 phosphorylation and function are under investigation. An additional research focus in the Slingerland lab addresses how cross talk between liganded ER and receptor tyrosine kinases and Src signal transduction pathways may link transcriptional activity of the ER to its proteolytic degradation. Dr. Slingerland’s research laboratory continues to investigate mechanisms regulating the cell cycle, antiestrogen resistance and estrogen receptor regulation in normal and malignant breast cells. Recently, she has initiated new clinical trials of molecular targeted therapies to reverse antiestrogen resistance.

 

Biographical Information
Joyce Slingerland, MD, FRCP(C), Ph.D., Director, Braman Family Breast Cancer Institute at the University of Miami Sylvester Comprehensive Cancer Center (UMSCCC).
A native of Canada, Dr. Slingerland received her M.D. from the University of Toronto in 1983, followed by a Fellowship in Internal Medicine with the Royal College of Physicians and Surgeons in Canada. In 1987, she was certified by the American Board in Internal Medicine and in Medical Oncology by the Royal College of Physicians and Surgeons. In August of 2002, Dr. Slingerland came to the University of Miami School of Medicine as the Director of the Braman Breast Cancer Institute, Sylvester Comprehensive Cancer Center where she is working to expand and coordinate research efforts on breast cancer from many disciplines. Dr. Slingerland is also Professor of Medicine with a graduate appointment in the Department of Biochemistry and
Molecular Biology at the University of Miami, as well as a member of the senior leadership of the UMSCCC and Co-Program Leader of the UMSCCC’s Molecular Oncology and Experimental Therapeutics Program. Dr. Slingerland continues her medical practice devoted entirely to breast cancer patients at the Sylvester Comprehensive Cancer Center and the Jackson Memorial Hospital. She has published over 50 articles and reviews in addition to several book chapters and has received numerous awards. The Slingerland’s lab has been funded by the Canadian NCI’s Breast Cancer Research Initiative and by the DOD Breast Cancer Research Program and now the US NCI. Her research has provided insights on how cancers escape negative growth controls. Dr. Slingerland has made the innovative discovery of the cell cycle inhibitor, p27, and showed that p27 deregulation is prognostic of
poor patient outcome and leads to antiestrogen resistance in estrogen receptor positive breast cancers.

 

Representative Publications

1.    L J. Ess

Govindarajan, B., Sligh, J., Vincent, B., Li, M., Canter, J., Nickoloff, B. J., Rodenburg, R. J., Smeitink, J. A., Oberley, L., Zhang, Y., Slingerland, J., Arnold, R. S., Lambeth, J. D., cohen, C., Hilenski, L., Greindling, K., Martinez-Diez, M., Cuezva, J. M., Arbiser, J. L. (2007) Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. Journal of Cancer Investigation

        Chu, I., Sun J., Arnaout, A., Kahn, H., Hanna, W., Narod, S., Sun, P., Tan, C., Hengst, L., and Slingerland, J. (2007) p27 Phosphorylation by Src regulates inhabitation of cyclin E-Cdk2. Cell 128: 1-14

Liang, J, Shao, S. H., Xu, Z., Hennessy, B., Ding, Z., Larrea, M., Kondo, S., Dumont, D. J., Gutterman, J. U., Walker, C. L., Slingerland, J. M., Mills, G. B. (2007) The energy sensing LKB1-AMPK pathway regulates p27kip1

phosphorylation mediating the decision to enter autophagy or apoptosis. Nature Cell Biology {e-pub ahead of print)

       S. Dhananjayan, O. Y. Khan, J. Slingerland and Z. Nawaz. (2006) Identification and characterization of WW-domain binding proteins as E6-AP interacting proteins and their role in steroid hormone receptor functions. Mol. Endo.