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Molecular and developmental biology of the lung and uterus
The goal of my laboratory is to investigate the molecular regulation of cellular differentiation and physiology. This
research is conducted on two model organ systems, the lung and uterus. Although these two tissues are significantly divergent in their
biological functions many of the molecular mechanisms regulating the cellular differentiation and physiology are conserved. In order to
investigate the biology of these tissues, my laboratory has manipulated the mouse genome to generate novel animal models to identify
molecular mechanisms regulating the cell biology of these organs.
The lung is composed of 40 different cell types. This makes the lung an interesting organ to investigate the developmental control
of cellular differentiation. The pulmonary cell types my laboratory is interested in investigating are the Clara cells, the neuroendocrine
cells and the alveolar type II cells. Clara cells are the non-ciliated secretory cells of the pulmonary epithelium. My laboratory has used
transgenic technology to execute in vivo promoter analysis to investigate the molecular regulation of Clara cell gene expression. The
information gained from these studies has allowed us to generate an animal model for lung cancer, to generate cell lines to further
investigate the elements regulating Clara cell differentiation and finally to determine how elements involved in lung development play a
role in the regulation of the response of the Clara cell to environmental challenges. In the investigation of the factors that control
neuroendocrine cell differentiation, my laboratory is interested in identifying what factors regulate neuroendocrine cell differentiation
as well as determining the role of these cells in damage and repair of the pulmonary epithelium. We have shown that the transcription
factor, achaete-scute, can cause a transformed Clara cell to express markers of neuroendocrine differentiation in vivo. Finally, in the
investigation of the biology of the alveolar type II cell, my laboratory has developed an transgenic "Gene-Switch" system to investigate how
growth factors which are involved in regulating lung development can function to regulate the biology of the alveolar type II cell in the
adult.
The uterus functions to support the development of the fetus. The ability of the embryo to attach and thrive in the uterus is under
tight hormonal control. Ablation of the receptor for the steroid hormone progesterone has demonstrated that this hormone is critical for
the uterus to initiate and support the implanting embryo. My laboratory is interested in understanding the cascade of events regulated by
progesterone. This is being accomplished by using current techniques in gene expression analysis to determine which genes are regulated by
progesterone. Finally my laboratory is generating novel approaches to investigate the role of specific genes in uterine biology in vivo.
The overall goal of the above studies in the understanding of the molecular regulation of cellular differentiation and
physiology is to shed light on pathways to aid in the diagnosis and treatment of human disease. Understanding the molecular regulation of
pulmonary cell differentiation will help design treatments for pulmonary diseases such as lung cancer, and asthma. The investigation of
uterine biology will aid in the treatment of infertility.
Selected Publications
Ramsay PL, Luo Z, Magdaleno SM, Whitbourne SK, Cao X, Park MS, Welty SE, Yu-Lee LY, DeMayo FJ (2003)
Transcriptional regulation of CCSP by interferon-γ in vitro and in vivo. American Journal of Physiology - Lung Cellular
and Molecular Physiology 284:L108-118.
Ramsay PL, Luo Z, Major A, Park MS, Finegold M, Welty SE, Kwak I, Darlington G, Demayo FJ (2003) Multiple
mechanisms for oxygen-induced regulation of the Clara cell secretory protein gene. FASEB Journal 17:2142-2124.
Jeong JW, Lee KY, Kwak I, White LD, Hilsenbeck SG, Lydon JP, Demayo FJ (2005) Identification of murine uterine genes
regulated in a ligand-dependent manner by the progesterone receptor. Endocrinology 146:3490-3505.
Jeong JW, Kwak I, Lee KY, White LD, Wang XP, Brunicardi FC, O'Malley BW, DeMayo FJ (2006) The genomic analysis of
the impact of steroid receptor coactivators ablation on hepatic metabolism. Molecular Endocrinology 20:1138-1152.
Jeong JW, Lee KY, Lydon JP, DeMayo FJ (2006) Steroid hormone regulation of Clca3 expression in the murine uterus.
Journal of Endocrinology 189:473-484.
Lee K, Jeong J, Kwak I, Yu CT, Lanske B, Soegiarto DW, Toftgard R, Tsai MJ, Tsai S, Lydon JP, DeMayo FJ (2006) Indian
hedgehog is a major mediator of progesterone signaling in the mouse uterus. Nature Genetics 38:1204-1209.
Lee K, Jeong J, Tsai MJ, Tsai S, Lydon JP, DeMayo FJ (2006) Molecular mechanisms involved in progesterone receptor
regulation of uterine function. Journal of Steroid Biochemistry and Molecular Biology 102:41-50.
Contact Information
- Francesco J. DeMayo, Ph.D.
- Department of Molecular and Cellular Biology
- Baylor College of Medicine
- One Baylor Plaza M725A
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-6241
- Fax: (713) 790-1275
- E-mail: fdemayo@bcm.tmc.edu
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