Current Interests

The laboratory efforts are focused on developing cell-based screens that will allow identification of novel pharmacophores targeted to renal cell carcinoma (RCC). Approximately 30,000 individuals per year in the US are diagnosed with RCC; one third present with metastatic disease. At present, little or no systemic therapy is available. Applied and basic research approaches are taken.

1. Cell-Based Screen Directed at the b-catenin Pathway. Because b-catenin, a transcription factor that regulates cell growth and survival, plays an integral part in oncogenesis, a high throughput screen that detects changes in its translocation to the nucleus is being developed. "Screening" hits will be evaluated using a bioinformatic approach that may define a common pharmacophore. Potential leads will be further studied based on novel chemical structures and/or targets.

2. Intrinsic Drug Resistance Mediated by the Extracellular Matrix (ECM). Recent findings support a role for the ECM in mediating drug resistance in RCC. Although this drug resistance can be extreme, it does depend on the cell line and compound under evaluation. Notably, almost all compounds that have clinical utility were found to be largely ineffective. Thus, studies are aimed at evaluating the mechanisms of intrinsic drug resistance in this model. Furthermore, this in vitro model allows for the development of a cell-based screen aimed at discovering compounds that have a sensitivity profile in RCC.

Interactive Interests

- Bioinformatics with expertise in the 3-D Mind Toolkit (http://spheroid.ncifcrf.gov).

- Hypothesis development linking molecular targets and compounds.

- 3-D Molecular Modeling using commercially available software such as Catalyst and Ras-Mol.

Credentials

Dr. Mertins received her Ph.D. in 1995 from the Department of Microbiology and Immunology at the George Washington University, Washington DC. She also received her B.S. (1980) and M.S. (1984) from the Biology Department in the same institution. Dr. Mertins has over 20 years of experience in laboratory research.

Recent Publications

Mertins, SD, Meyers, T, Bodde, E, Tsai, P, Jefferis, C, Gupta, R, Linehan, WM, Alley, M, Bates, SE. 2001. Screening for and identification of novel agents directed at renal cell carcinoma. Clin Can Res 7: 620.

Sandor, V, Senderewicz, A, Mertins, SD, Sackett, D, Sausville, E, Blagosklonny, MV, Bates, SE. 2000. P21-dependent G1 arrest with down regulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228. Br J Cancer 83: 817.

Mertins, SD, Gamelin, E, Regis, JT, Mickley, L, Abati, A, Worrell, RA, Linehan, WM, Bates, SE. 1999. Comparison of drug resistance in primary and metastatic renal carcinoma (RCC) lines. J Urol 162: 217