Structure, function, and regulation of galectins. 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 of galectins (a family of beta-galactoside-binding lectins) and their interactions with the carbohydrates that mediate cell-cell and cell-extracellular matrix (ECM) interactions during normal and cancer development such as prostate and breast cancers. The prostate cancer cells differentially express several members of galectins, which alter normal cell-cell and cell-ECM interactions during cancer development. We have discovered a novel isoform of galectin-8 that may be relevant to prostate cancer cell proliferation. Further, we have demonstrated cytosine methylation in galectin promoter in cancerous prostate, which may account for the differential expression of galectins during cancer development. Differential expression of galectin repertoire and identification of cytosine methylation of galectin gene promoters in normal and prostate tissues are now being employed to develop sensitive tools for early diagnosis of prostate cancer in biological fluids such as serum and urine. In another project, natural carbohydrate inhibitors of galectin are being employed to prevent breast cancer metastasis.

Lectin-nanoparticle conjugates to target cancer cells. Nanoparticles (nanometer size range) provide a new mode of cancer drug delivery as they function as a carrier for entry through fenestrations in tumor vasculature allowing direct cell access. These particles allow exquisite modification for binding to cancer cell membranes, the microenvironment, or to cytoplasmic or nuclear receptor sites. Although this results in delivery of high drug concentrations to the targeted cancer cell, a considerable amount of normal cells are damaged and thus new technology is needed to reduce injury of normal cells. In collaboration with Dr. Silvia Muro (CBR, UMBI), lectin-nanoparticle conjugates are being analyzed not only for delivering drugs specifically to cancer cells, but also for detection of cancer cells by imaging technologies.

Zebrafish as a model organism for studying human cancer. The zebrafish is emerging as a powerful cancer model system as zebrafish neoplasms are in many cases similar to human cancers. The main advantages of zebrafish as a model organism are short generation times and transparent embryos that develop externally. Moreover, they are cheap and they don't need much space. Zebrafish can be genetically manipulated, both via reverse and forward genetics. In addition to these techniques, small molecule screens and genetic modifier screens are relatively easy to perform in zebrafish. Particularly, I am 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 mammalian DNA methylation and the assembly of the genetic networks that regulate normal development and oncogenesis.