Our Science – Kimura Website

Shioko Kimura, Ph.D.

Laboratory of Metabolism Head, Endocrinology Section Senior Investigator Building 37, Room 3112B NCI-Bethesda Bethesda, MD 20892 Phone:   301-496-0958 Fax:   301-496-8419 E-Mail:   shioko@helix.nih.gov Link: Other Homepage

Biography

Dr. Kimura obtained her Ph.D. in chemistry in 1979 at Hokkaido University, Sapporo, Japan. After 3 years of postdoctoral study at Queen's University, Kingston, Ontario, she joined the National Institute of Child Health and Human Development as a visiting fellow. In 1986, she moved to the Laboratory of Molecular Carcinogenesis, NCI. Since 1996, she has been head of the Endocrinology Section, Laboratory of Metabolism.

Research

Role of Thyroid-Specific Enhancer-Binding Protein in transcription, physiology, and development

Our research interest is to understand the mechanisms of differentiation and maintenance of homeostasis of the thyroid and lung. Particularly, current efforts are focused on understanding the role of the thyroid-specific enhancer-binding protein (T/EBP) in transcription, physiology, and development. T/EPB, also called TTF1 (thyroid transcription factor 1) or NKX2.1, is a homeodomain transcription factor that regulates expression of thyroid and lung-specific genes, including those encoding thyroid peroxidase, thyroglobulin, TSH receptor, and the Na/I symporter in the thyroid, and surfactant proteins A, B, and C, and clara cell secretary protein in the lung. T/EBP is expressed in the thyroid, lung, and ventral forebrain during early embryogenesis. Mice lacking T/EBP expression die at birth, missing the thyroid and pituitary and having severe defects in the lung and hypothalamus. T/ebp-null mice thus unequivocally demonstrate that T/EBP is essential for genesis of these organs. Based on the detailed analyses of the defects in each organ, T/EBP appears to qualify as one of the master regulatory genes involved in morphogenesis of the thyroid, lung, and pituitary, which either activates or suppresses downstream target genes, ultimately leading to organ development. Our efforts have focused on identifying genes that are regulated by T/EBP during mammalian development and that are involved in organogenesis.

In order to understand the role of T/EBP during development and in the homeostasis of the thyroid and lung, conditional knockout mouse lines using the Cre-Lox P system that deletes T/EBP expression only in the thyroid or lung have been developed. A three dimensional thyroid primary culture system was also developed to study the role of T/EBP in thyroid differentiation in vitro. Studies using T/EBP-thyroid conditional knockout mice and three dimensional thyroid primary cultures demonstrated that T/EBP is required for maintenance of the normal architecture and function of differentiated thyroids. Furthermore, thyroid phenotypes of the T/EBP-thyroid conditional knockout mice suggested the possible presence of a stem-cell like population of cells in the thyroid, and T/EBP may be involved in maintaining such a population of cells. Based on the hypothesis that mice with deleted T/EBP may be susceptible to carcinogens, chemical carcinogenesis studies are in progress using the T/EBP-thyroid conditional knockout mice.

Another research project ongoing in the Endocrinology Section is to characterize Uteroglobin-related protein (UGRP) 1, also named SCGB(secretoglobin)3A2, originally identified as a T/EBP downstream target gene in the lung. UGRP1 is a homodimeric secretory protein of approximately 10 kDa that is highly expressed in epithelial cells of the trachea, bronchus and bronchioles. Several characteristics of UGRP1 suggested that UGRP1 may play a role in lung inflammation. In order to understand the role of UGRP1 in lung inflammation, ovalbumin-sensitized and challenged mice, a model for allergic bronchial asthma, were used in conjunction with recombinant adenovirus expressing UGRP1. These results demonstrated that UGRP1 can suppress allergic airway inflammation in a mouse model of allergic bronchial asthma. In order to confirm this question, we are in process of producing UGRP1-conditional knockout mouse that specifically deletes UGRP1 only in lung and transgenic mouse that over-expresses UGRP1 in lung epithelial cells. These mice will be subjected to experimental allergic inflammation model where the effect of loss or gain of UGRP1 on the inflammatory status will be examined.

This page was last updated on 6/11/2008.