Francesco J. DeMayo, Ph.D.
Professor, Department of Molecular and Cellular Biology
Ph.D., Michigan State University
Postdoctoral, Baylor College of Medicine
Research Interests:
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 significant 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 cel types my laboratory is interested in investigation 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, achete schute, can cause a transformed Clara cell to express markers of neuroendocrine differentiation in vivo. Finally, in the investigator of the biology of the alveolar type II cell my laboratory has developed an transgenic "Gene Switch" (see figure below) 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 investigations 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:
Jeong JW, Kwak I, Lee KY, White LD, Wang XP, Brunicardi FC, O'Malley BW and DeMayo FJ. (2006). The genomic analysis of the impact of steroid receptor coactivators ablation on hepatic metabolism. Mol Endocrinol 20, 1138-1152.
Jeong JW, Lee KY, Lydon JP and DeMayo FJ. (2006). Steroid hormone regulation of Clca3 expression in the murine uterus. J Endocrinol 189, 473-484.
Lee K, Jeong J, Kwak I, Yu CT, Lanske B, Soegiarto DW, Toftgard R, Tsai MJ, Tsai S, Lydon JP and DeMayo FJ. (2006). Indian hedgehog is a major mediator of progesterone signaling in the mouse uterus. Nat Genet 38, 1204-1209.
Lee K, Jeong J, Tsai MJ, Tsai S, Lydon JP and DeMayo FJ. (2006). Molecular mechanisms involved in progesterone receptor regulation of uterine function. J Steroid Biochem Mol Biol 102, 41-50.
Jeong JW, Lee KY, Kwak I, White LD, Hilsenbeck S G, Lydon JP and DeMayo FJ. (2005). Identification of murine uterine genes regulated in a ligand-dependent manner by the progesterone receptor. Endocrinology 146, 3490-3505.
Ramsay PL, Lu, Z, Magdaleno SM, Whitbourne SK, Cao X, Park MS, Welty SE, Yu-Lee LY, and DeMayo, FJ. (2003). Transcriptional regulation of CCSP by interferon-gamma in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 284, L108-118.
Ramsay PL, Luo Z, Major A, Park MS, Finegold M, Welty SE, Kwak I, Darlington G and Demayo FJ. (2003). Multiple mechanisms for oxygen-induced regulation of the Clara cell secretory protein gene. Faseb J 17, 2142-2144.
For more publications, see listing on PubMed.
Contact Information:
Francisco J. DeMayo, Ph.D.
(713) 798-6241
Fax: (713) 790-1275
E-mail: fdemayo@bcm.edu
Updated 8/07