My research goals and objectives are focused mainly on understanding the molecular basis of cancer by identifying the genes involved in this process and translating this information for possible targeted therapy of cancer.

Identification of molecular targets for immuno-based therapy of cancer. Expressed sequence tags (EST) are sequences derived from randomly selected clones from various cDNA libraries. Each cDNA clone is generated from a transcript and the frequency and distribution of the many different transcripts in any given tissue depends on the tissue-specific activity of genes. Therefore ESTs provide a valuable source of information that may be utilized to predict the expression patterns of certain genes in different tissues. There are many ways by which the vast amount of EST sequence data can be processed to cluster, sort and filter the cDNA sequences, with the goal of identifying genes that are specifically expressed in certain tissues. Using various bioinformatics tools in combination with experimental verification, we have identified several new genes that are specifically expressed in prostate cancer and in normal prostate but not in essential tissue. NGEP is a new gene encoding plasma membrane protein specifically expressed in normal prostate and prostate cancer. Because of its restricted expression in prostate cancer and encoding a plasma membrane protein, NGEP is a promising molecular target for immuno-based therapy of prostate cancer.  We are in the process of developing monoclonal antibodies to NGEP and eventually will develop immunotoxin targeting prostate cancer.

New model for obesity and gigantism due to disruption of the Ankrd26 gene. During our effort to identify cancer-specific membrane protein as an immuno-based therapeutic target, we have identified a primate-specific gene family, POTE. Although POTE protein is associated with the inner membrane of the cell, it is not an integral membrane protein and thus not an ideal candidate for immuno-based targeted therapy. Expression of the POTE gene is restricted to very few normal tissues but its expression is induced in various cancers, suggesting a role for this gene in cancer. To gain some insight into the biological function of POTE gene family, we have identified the POTE ancestor gene ANKRD26, and its mouse ortholog. Using a  "gene knock-out" approach, we have generated mutant mice with inactivation of the Ankdr26 protein. Homozygous Ankrd26 mutant mice with partial inactivation of the protein develop extreme obesity and an increase in organ and body size.

In the future we would like to use a "conditional gene targeting" approach to generate a tissue-specific knock-out of the Ankrd26 gene to understand its function in different organs. the Ankrd26 gene is expressed in many adult organs as well as during embryogenesis. Several organs, including heart, liver and kidney, grow larger due to partial inactivation of Ankrd26 gene. We would like to study the role of Ankrd26 during normal development as well as during carcinogenesis for these organs in tissue-specific null mice.