My research interest has been in the area of basic and translational research of the carbohydrate-binding proteins (called lectins). Particularly, I am interested in structure, function and regulation (including epigenetic regulation) of galectins (beta-galactoside-binding lectins) and their interactions with the carbohydrates that mediate cell-cell and cell-extracellular matrix interactions during normal and cancer development.
We have recently discovered that the expression of galectin-3 is negatively correlated with the DNA (cytosine) methylation in its promoter. In early stages of prostate cancer, expression of galectin-3 was found silenced. We have demonstrated that the galectin-3 promoter in early stages of prostate cancer is heavily methylated. No methylation was observed in the galectin-3 promoter of either normal or benign prostate hyperplasia tissue. Differential expression of galectin-3 and its cytosine methylation in the promoter region in various stages of prostate cancer allow development of sensitive and specific tool (methylation-specific PCR assay) for early diagnosis of prostate cancer. A quantitative MS-PCR assay is now being developed for early diagnosis of prostate cancer in biological fluids such as serum and urine. A part of my current project has recently been funded by NIH.
Galectin-3 is believed to cause breast cancer metastasis by promoting angiogenesis and tumor-endotheilial cell interactions. In addition to its role in cancer metastasis by promoting angiogenesis and cancer-infiltrating T cells and thus facilitates tumor progression. In this DOD funded project, we are investigating the efficacy of the natural carbohydrate inhibitors of galectin-3 to prevent breast cancer metastasis. For this purpose, a TF-disaccharide-rich fraction has been isolated from edible fish. In our preliminary experiments, this natural compound inhibited galectin-3-mediated tumor-endothelial cell interactions. Moreover, this compound prevents galectin-3-mediated T cell apoptosis. Investigation of downstream signaling under varioius conditions is underway.
We are also developing zebrafish model for studying human cancers. The zebrafish is emerging as a powerful cancer model system as zebrafish neoplasms are in many cases similar to human cancers. Particularly, we are interested in developing methylation microarray specifically focused on CpG islands of zebrafish promoters. For this purpose, zebrafish are chemically induced to develop a specific cancer and then methylation pattern of genes are analyzed to gain insight into mammaliam DNA methylation and the assembly of the genetic networks that regulate normal development and oncogenesis. We are also working on the development of transgenic zebrafish for studying leukemia.
Ahmed, H., Du, S.J., and Vasta, G.R. 2009. Knockdown of a galectin-1-like protein in zebrafish (Danio rerio) causes defects in skeletal muscle development. Glycoconjugate J. 26, 277-283.
Mercer, N., Guzman, L., Cueto Rua, E., Drut, R., Ahmed, H., Vasta G.R., Toscano, M.A., Rabinovich, G.A., and Docena, G.H. 2009. Duodenal intraepithelial lymphocytes of children with cow milk allergy preferentially bind the glycan-binding protein galectin-3. Int. J. Immunopathol. Pharmacol. 22, 207-217.
Ahmed, H., Cappello, F., Rodolico, V., and Vasta, G.R. 2009. Evidence of heavy methylation in the galectin-3 promoter in early stages of prostate adenocarcinoma: Development and validation of a methylated marker for early diagnosis of prostate cancer. Translational Oncol. 2, 146-156.
Ahmed, H. 2009. Epigenetics of galectin-3: A novel regulatory mechanism of its transcription during carcinogenesis. In: Experimental Medicine Review, Vol. II (Eds. A. Gerbino, G. Zummo, and G. Crescimanno) (In press).
Ahmed, H. 2009 Promoter methylation in prostate cancer and its application for early detection in serum and urine. Biomarkers in Cancer (In revision).