The American Thyroid Association (ATA) announced the five recipients of its 2011 research grants, each of whom will receive up to $25,000 annually for up to two years. Three of the five recipients were awarded special ATA ThyCa grants for research projects that focus on thyroid cancer. These grants are funded by ThyCa: Thyroid Cancer Survivors, Inc. (ThyCa).
The 2011 ThyCa grant recipients are Naifa Busaidy, M.D., Assistant Professor, The University of Texas MD Anderson Cancer Center (Houston), Carmelo Nucera, M.D., Ph.D., Instructor/Junior Faculty, Beth Israel Deaconess Medical Center and Harvard Medical School (Boston, MA), and Joanna Klubo-Gwiezdzinsk, Ph.D., Endocrine Research Fellow, Washington Hospital Center/Georgetown University.
Dr. Busaidy, who received her medical degree from Baylor College of Medicine (Houston, TX) in 1997, is the recipient of a ThyCa grant to study "A PI3K based phosphoproteome signature to predict prognosis and response to therapy in BRAF mutant papillary thyroid carcinoma." While most patients with papillary thyroid carcinoma (PTC) respond well to conventional therapy (surgery and radioactive iodine), 15%-20% will suffer recurrent PTC that is resistant to radioactive iodine or metastatic disease. Dr. Busaidy proposes to determine whether activation of the PI3K/AKT pathway in PTC tumors carrying a BRAF mutation—a pathway that has been implicated in aggressive thyroid cancers—is predictive of clinical outcomes and response to treatment.
Dr. Nucera completed his medical and doctoral degrees and a residency in Endocrinology and Metabolic Diseases at the University of Messina, Italy. His research will focus on "Targeting BRAFV600E with an orally available selective inhibitor in novel in vitro and in vivo preclinical models of human papillary thyroid cancer." A large percentage of patients with radioactive iodine-resistant PTC carry a genetic mutation called BRAFV600E, resulting in decreased expression of the genes involved in iodide transport and metabolism. Dr. Nucera will assess the effects of LX4032, an oral drug that selectively inhibits BRAFV600E kinase, on PTC-derived cells in culture and on PTC tumor aggressiveness in mouse models.
Dr. Klubo-Gwiezdzinska obtained her degrees from Collegium Medicum in Bydgoszcz and Nicolaus Copernicus University in Torun, Poland. She received a ThyCa grant to study "The role of the translocator protein (TSPO) in the thyroid cancer response to treatment." Her project will focus on the molecular mechanisms underlying thyroid cancer response to radioiodine therapy and the ability to predict which tumors are more likely to be resistant to conventional treatment. Dr. Klubo-Gwiezdzinska will explore whether expression of the mitochondrial membrane translocator protein (TSPO) correlates with tumor response to radiation in vitro and whether TSPO expression can affect thyroid cancer cell response to radiation in vivo.
Recipients of the two general ATA research grants are Mihaela Stefan, Ph.D., Assistant Professor, Mount Sinai School of Medicine (New York, NY), and Inna Astapova, Ph.D., Instructor in Medicine, Beth Israel Deaconess Medical Center (Boston, MA).
Dr. Stefan, who received his doctoral degree in Genetics from University of Bucharest, Romania, in 2000, will study the "Role of interferon alpha in development of AITD: Epigenetic regulation of key genes." In autoimmune thyroid diseases (AITD), in which a person's own immune system attacks and damages the thyroid gland, individuals with certain genetic variations are predisposed to develop AITD when exposed to associated environmental factors. Dr. Stefan proposes to identify the epigenetic mechanisms that mediate these gene/environment interactions by studying changes in gene expression triggered by interferon that result in AITD. The research team will analyze genome-wide DNA methylation patterns in thyroid cells exposed to interferon in vitro, and will study the effect of interferon on the epigenome in transgenic mice that express human interferon. In the future it may be possible to target these changes in gene expression to prevent and treat AITD.
Dr. Astapova completed her Ph.D. in Molecular Biology in 2001 at the Russian Academy of Sciences. Her grant application is entitled, "Elucidating the in vivo mechanisms by which thyroid hormone regulates energy expenditure." Dr. Astapova and colleagues recently produced a mouse model that expresses a mutant form of the NCoR protein, a protein believed to have an essential role in thyroid hormone signaling through the activation of nuclear thyroid hormone receptors. They will use this mouse line to study the mechanisms involved in the ability of thyroid hormone to regulate energy expenditure in mammals. The ability to understand these pathways could lead to novel approaches to treating metabolic diseases by manipulating thyroid hormone activity.
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