Summary: Our group utilizes organic chemistry towards synthesis of cell permeable medicinally active small molecules. For example, we are developing small molecules in understanding the physiological and biochemical role of ceramide metabolizing enzymes. Ceramide is a bioactive sphingolipid that exhibits anticancer properties in a cell. Strategies aimed at increasing the cellular ceramide induce apoptosis in cancer cells. To complement our synthetic efforts, we perform in vitro experiments and cell-based assays towards determining the biological activity of these analogs in a structure-activity relationship model.

Minimum classes: General chemistry/organic chemistry/biochemistry

Projects:  A. Synthesis, structure-activity relationship studies of small molecules in understanding the biological relevance of ceramide metabolizing enzymes. This project involves synthesis of natural product-based analogs or natural product-like analogs followed by in vitro based assays towards quantification of cellular ceramide levels. Several studies demonstrated that increase in cellular ceramide concentration resulted in inducing apoptosis in cancer cells. We hypothesize that by blocking ceramide metabolism we can modulate the cellular ceramide concentrations and induce apoptosis in cancer cells.

B. Identification of medicinally active small molecules to inhibit glycation of histone proteins. Glycation, a type of covalent modification of protein, observed at higher incidence under oxidative stress conditions. Histones maintain DNA integrity. Glycation of histones at the genomic level disrupts the integrity of DNA resulting in deleterious effects. We hypothesize that by minimizing these covalent modifications of histones especially under oxidative stress conditions we can minimize the DNA damage. We use natural product-based phytochemicals as glycation inhibitors.

Our research projects outlined above are collaborative and multidisciplinary in nature. Students trained in biochemistry or organic chemistry or both disciplines can participate in these projects.

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