The American Thyroid Association's (ATA) Sidney H. Ingbar Distinguished Lectureship Award recognizes outstanding academic achievements in thyroidology. An honorarium is conferred each year at the ATA Annual Meeting to an established investigator who has made major contributions to thyroid-related research over many years. The award is endowed by contributions made in honor of the memory of Sidney H. Ingbar and in recognition of the innovation and vision that epitomized his brilliant investigative career.
This year's Sidney H. Ingbar Distinguished Lectureship Award recipient is Gregory Brent, MD, Professor of Medicine and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, and Chief, Endocrinology and Diabetes Division, VA Greater Los Angeles Healthcare System. He will receive this Award on October 28, 2011, at the 81st Annual Meeting of the ATA, in Indian Wells, California.
Dr. Brent's research interests focus on gene regulation by nuclear acting hormones, particularly thyroid hormone and retinoic acid. His laboratory explores the molecular mechanisms of thyroid hormone action and iodine transport in hormone-dependent cancers.
Dr. Brent has conducted research in the area of the thyroid for nearly 25 years, and early in his career made the landmark clinical observation that a woman's thyroid hormone requirements increase during pregnancy. Women with hypothyroidism may need a higher maintenance dose of thyroid hormone during their pregnancy to avoid potentially adverse affects on the cognitive development of the fetus. This had been an area of continuing clinical interest, and Dr. Brent has contributed to the planning of two ATA Spring Symposia on the topic of thyroid dysfunction in pregnancy.
As a result of his research on the mechanisms of hormone-mediated gene regulation, he was the first to report that thyroid hormone receptor binds to direct-repeat DNA response elements. Furthermore, he characterized positive and negative hormone-response elements across a range of genes and made the crucial observation that response element sequence and position are important in conferring negative gene regulation by thyroid hormone. Dr. Brent also demonstrated thyroid hormone receptor isoform specificity in recognition of DNA response elements.
Other key research contributions include the effects of thyroid hormone gene regulation on neural differentiation and mechanisms of metabolic regulation. Dr. Brent was the first researcher to utilize in vitro embryonic stem cell differentiation to study deletions and mutations in the thyroid hormone receptor gene and to characterize their influence on cell differentiation and gene expression. He created a mouse with a mutant thyroid receptor alpha gene and used isoform-selective agonists to study the underlying mechanisms of thyroid hormone metabolic regulation, including adrenergic sensitivity in brown fat, lipolysis in white fat, and antagonism of hepatic PPARα signaling. He discovered that two distinct thyroid receptor-dependent pathways—stimulation of uncoupling protein1 and augmentation of adrenergic responsiveness—are mediated by different receptor isoforms in the same tissue, brown fat. He demonstrated that the thyroid receptor alpha mutant antagonizes PPARα signaling and impairs fatty acid oxidation.
Dr. Brent has also studied sodium iodide symporter (NIS) regulation in thyroid cancer and made the novel observation that retinoids stimulate NIS gene expression and radioiodide concentration, demonstrating this phenomenon in both in vitro and in vivo models of breast cancer. He has reported that retinoids activate NIS in breast cancer via both nuclear and non-nuclear pathways and that retinoic acid receptors directly modulate signal transduction signals through interactions with PI3 kinase.
Study reveals how cancer cells evade chemotherapy in low-glucose environments