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B.A., University of Colorado, Denver, CO 1986
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Ph.D., University of Arizona, AZ 1990
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Postdoctoral, ETH-Zurich 1991
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Postdoctoral, University of Washington, WA 1991-1992
PUBLICATIONS
Research
Dr. Arterburn’s research program focuses on the development of small molecular probes, imaging agents, anticancer and antiviral drugs. We employ innovative strategies using modern methods of organic and organometallic synthetic chemistry for the synthesis of conjugates, broadly impacting the multidisciplinary fields of drug development and chemical biology, and addressing fundamental problems in chemistry, biology and medicine. One representative major success story stems from a long-standing commitment to cancer research. In this field, his work involving the synthesis of estrogen imaging agents, and a productive research collaboration with Dr.’s Prossnitz, Oprea, Hathaway and Sklar from the UNM Cancer Center, has recently revealed an entirely new type of estrogen receptor named GPR30 (also called GPER). This receptor is found in breast, ovarian and endometrial tissues, as well as in aggressive cancer cell lines that lack other estrogen receptors. It is also associated with lower survival rates in endometrial cancer patients, and higher risk of developing metastatic disease in breast cancer. The importance of the nuclear estrogen receptors ER?/? to breast cancer is widely recognized among cancer researchers. GPR30 mediates some of the same cellular responses as the conventional estrogen receptor but utilizes distinct biochemical signaling pathways. Anti-estrogen drugs such as Tamoxifen and Faslodex, were developed to target the classical forms of estrogen receptors. However, such anti-estrogens can produce unexpected and potentially harmful interactions in cells that harbor GPR30. Because of the importance of estrogen-mediated signaling in breast, ovarian and endometrial cancers, GPR30 is believed to play an important role in the development and/or progression of these cancers. GPR30 may represent both a novel biomarker for diagnostic/prognostic/treatment stratification. It may also provide a therapeutic focus for the targeted treatment of these cancers. We have developed new diagnostics, imaging agents, and therapeutics based on the synthetic tetrahydro-3H-cyclopenta[c]quinoline scaffold that selectively target GPR30. We are designing new agents capable of detecting GPR30 as a biomarker by non-invasive imaging for early diagnosis, and to control its activity in order to alter the course of cancer formation and progression. The teams’ initial 2005 publication in Science described GPR30-estrogen binding and non-genomic signaling pathways, a subsequent 2006 paper in Nature Chemical Biology reported the discovery of the first GPR30 selective agonist G-1, the synthesis and in vivo characterization of the first GPR30 antagonist G15 was published in Nature Chemical Biology in 2009, and a second generation GPR30 antagonist G36 was recently published in J. Steroid Biochem & Mol Biol. These probes are currently being used in laboratories around the world to distinguish GPR30-mediated physiological effects and have already attracted tremendous scientific interest. U.S. patent S.N. 11/497,751 was awarded for this invention, and N12-071USDIV divisional application was filed recently to include isotopically labeled analogs for biomedical applications.
Dr. Arterburn’s cancer research interests include other projects that involve development of small molecule regulators to control key steps in cancer cell biology, that have potential for development as new selective anticancer drugs and diagnostic agents. Collaborative studies with Dr. C. Brad Shuster in the NMSU Department of Biology have identified a promising new class of inhibitors of the kinesin 5 motor protein Eg5 as potential anticancer drugs. We have recently developed a variety of fluorescent probes, including a new triazaborolopyridinium scaffold, derived from hydrazinyl pyridine these “HPY-Dyes” are membrane permeable, exhibit tunable photophysical properties, and serve as excellent partners for the construction of small molecule-based fluorescent probes. Several additional productive chemical biology, and cancer research collaborations are ongoing.
A second major focus of Dr. Arterburn’s research program involves the development of novel antiviral drugs for treating emerging and reemerging RNA viruses. These viruses pose a growing threat to global health. These include hantavirus, first recognized by the outbreak in the Four Corners region of the U.S. and dengue fever virus that looms frighteningly close to our international border location with Mexico. No licensed vaccines or antiviral therapeutics are currently available to treat infections caused by either of these viruses. Dr. Arterburn has synthesized new structurally-modified nucleoside analogs that preferentially target viral replication, icluding compounds that produce mutations in the viral genome that result in decreased fitness and ultimately extinction of the virus. This approach offers great promise to provide new drugs with broad-spectrum activity to combat multiple viral diseases, using a mechanism of action that is compatible with combination drug therapy. It may also help to avoid the development of antiviral drug resistance and also reveal fundamental information on viral biology. A collaborative investigation with Dr. K. Hanley in the NMSU Department of Biology will investigate a new synergistic strategy to treat flavivirus infections. A major multi-institutional collaborative project to identify broadly cross-reactive antivirals for treatment of alphaviruses, and other highly pathogenic viruses in the families Bunyaviridae and Arenavirida that partners NMSU with the University of Louisville Center for Predictive Medicine, the University of New Mexico, and the United States Army Medical Research Institute of Infectious Diseases is in progress.
