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J. Don Chen, Ph.D. Department of Pharmacology Phone: (732)-235-3292 |
| Gene regulation by nuclear hormone receptors Molecular genetics of acute promyelocytic leukemia |
| Research Description: |
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The overall goals of our research program are (1) to understand the molecular mechanisms of gene regulation by steroid/nuclear hormone receptors, (2) to identify and clone new genes involved in regulating nuclear receptor function, and (3) to develop molecular tools to combat hormone related human diseases including acute promyelocytic leukemia, breast cancer and diabetes. Nuclear receptors are ligand dependent transcription factors that regulate genes critical to such biological processes as development, reproduction, and homeostasis. These receptors can function as molecular switches, alternating between states of repression and activation depending on the availability of cognate hormone. Our lab has cloned the first nuclear receptor corepressor SMRT that associates with the unliganded retinoid and thyroid hormone receptors to mediate transcriptional repression of target genes. SMRT and the related corepressor N-CoR are known to recruit histone deacetylase complex to modify chromatin structure for transcriptional repression. Our lab has also cloned the important nuclear receptor coactivator RAC3, also known as AIB1 for it is amplified in breast cancer. The RAC3 coactivator interacts with ligand-bound receptors, and then serves as a bridging factor to recruit additional coactivators such as CBP/p300 and P/CAF for acetylating histones and transcriptional activation. Finally, we have also cloned the pro-apoptotic protein Daxx based on interaction with the promyelocytic leukemic protein PML, which fuses with the retinoid acid receptor in t(15;17) translocation. Overall, we are interested in elucidating the molecular mechanisms that the PML-RAR oncoprotein uses to induce acute promyelocytic leukemia. Our lab is well equipped and highly committed to continue to identify new mechanisms and to clone new genes involved in hormone action. We have the state-of-art equipment and we utilize the latest technology in our daily research. We hope that one day our research will lead to development of new molecular tools or strategies to help combat hormone related human diseases.
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