Joyce M. Slingerland, M.D., Ph.D.
- American Board of Internal Medicine
- Internal Medicine
- Hematology/Oncology - Internal Medicine
- Associate Director, Translational Research
- Director, Braman Family Breast Cancer Institute at Sylvester Comprehensive Cancer Center
- Professor of Medicine
Dr. Slingerland's research interests include: breast cancer, molecular mechanisms of signal transduction and hormone effects on cell cycle regulation and breast cancer cell growth, breast cancer stem cells as targets for therapy and the role of estrogen receptors in breast cancer.
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. Src 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.