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Yen Wins Mentoring Award

By Anna Gillis

Dr. Paul M. Yen's lab came away from this year's Endocrine Society meeting with three honors. A senior investigator in NIDDK's Clinical Endocrinology Branch, Yen received the $30,000 Abbott Thyroid Research Mentor Award. Two fellows in his lab, Dr. Pnina Rotman-Pikielny and Dr. Shinichiro Ando, each received a $1,000 Abbott Thyroid Research Clinical Fellowship Award.

The fellows competed in oral presentations with four other young investigators conducting work on clinically important aspects of thyroid disease. "It is only the second time that two people from one lab were competing," says Yen, who himself won a 1993 Boots Pharmaceuticals Clinical Fellowship Award, the prize's earlier name. By winning the competition, Rotman-Pikielny made it possible for Yen to receive the Mentor Award. The prize money will be used to train future investigators interested in thyroid disease.

Mentor Dr. Paul Yen (c) confers with associates Dr. Pnina Rotman-Pikielny (l) and Dr. Shinichiro Ando.

Rotman-Pikielny presented her findings on pendrin, a protein that carries iodide out of cells in the thyroid gland. Mutations in the protein lead to Pendred syndrome, the primary cause of congenital deafness in the United States, and a cause of goiter and hypothyroidism. Until now, scientists had not identified how mutant pendrin causes disease. Rotman-Pikielny, in collaboration with Dr. Koret Hirschberg of NICHD and Dr. Padma Maruvada of the Yen laboratory, fused green fluorescent protein to normal and faulty pendrin and tracked where the proteins traveled in several different types of cells, including rat thyroid cells. She found that the flawed protein never gets to the cell's surface where it is supposed to go. Instead, it gets stuck in the endoplasmic reticulum, the network of tubules in the cell's cytoplasm where proteins are made. The finding suggests that Pendred syndrome may have to be added to a growing list of endoplasmic reticulum storage diseases that includes cystic fibrosis and diabetes insipidus.

Ando received his prize for showing for the first time that mutant thyroid hormone receptors can cause a dysregulation of thyroid-stimulating hormone in pituitary tumors that cause hyperthyroidism. The mutant thyroid hormone receptors were made by a mutation of thyroid hormone receptor DNA or an abnormal alternative splicing of thyroid hormone receptor RNA. The latter case showed for the first time that alternative splicing plays a role in creating abnormal thyroid hormone receptors. Because alternative splicing allows different pieces of mRNA to be cut out after transcription, one gene can produce several variations on a protein's basic structure. The DNA coding for the receptor was normal, but in going from DNA to RNA, key information was spliced out. Ando says if they had not looked at the RNA, they would not have found the underlying cause of the problem. "Sometimes it's not enough to just look at DNA for receptor mutations," he says.

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