Gretchen J. Darlington, Ph.D.
Professor
Department of Pathology
Huffington Center of Aging
Department of Molecular and Human Genetics
Department of Molecular and Cellular Biology
Department of Pediatrics
Baylor College of Medicine, Building: Alkek Tower Room:
ALKT-N803
Phone: 713.798.1565
E~mail: gretchen@bcm.tmc.edu
Research Interests: Mechanisms of Liver Injury and Tissue Specific Gene Expression
My laboratory is currently investigating the role of the C/EBP family of transcription factors in the acute phase or inflammatory response of the liver, and the gene expression patterns that correlate with longevity. Our laboratory has studied the molecular mechanisms that regulate the acute phase or inflammatory response and we have identified a number of factors that are important in the transcriptional regulation of the acute phase genes, including C/EBP family of transcription factors. In order to investigate the role of the C/EBP genes in vivo, we carried out experiments in which the C/EBPa gene was mutated in mice. The C/EBPa knockout mice have numerous interesting phenotypes, among them is the observation that in the newborn animals, the acute phase response is totally lacking. We are working to establish the molecular basis for the dependence of the inflammatory response on C/EBPa.
A second area of interest is the characterization of liver stem cells using gene expression profiling. Liver cell populations will be sorted using markers of hematopoietic stem cells and oval cells then tested by transplantation for their capacity to differentiate into hepatocytes and bile duct epithelium. The populations that have pluripotential properties will be characterized by microarray analysis for their patterns of gene expression. One goal will be to identify genes whose protein products may serve as markers for stem cells and that may be used to select the stem cells from a population of multiple cell types. A second goal is to use the gene expression patterns to make predictions about the biology of stem cells.
Selected Publications
Harris, T.E., Albrecht, J.H., Nakanishi, M. Darlington, G.J. CCAAT/enhancer-binding protein-alpha cooperates with p21 to inhibit cyclin-dependent kinase-2 activity and induces growth arrest independent of D. binding. In J Biol Chem, 276(31) 29200-9, 2001.Linhart, HG, Ishimura-Oka, K., DeMayo, F, Kibe, T, Repka, D, Poindexter, B, Bick, RJ, Darlington, G.J.C/EBP is required for differentiation of white, but not brown, adipose tissue. PNAS, 98(22); 12532-12537, 2001.
Collins, S.J., Ulmer, J., Purton, L.E., Darlington, G. Multipotent hematopoietic cell lines derived from C/EBP(-/-) knockout mice display granulocyte macrophage-colony-stimulating factor, granulocyte-colony-stimulating factor, and retinoic acid-induced granulocytic differentiation. Blood, 98(8):2382-8, 2001.
Carmona, MC, Iglesias, R., Obregon, M.J., Darlington, G.J., Villarroya, F., Giralt, M. Mitochondrial biogenesis and thyroid status maturation in brown fat require CCAAT/enhancer-binding protein alpha. J Biol Chem., 277(24); 21489-98, 2002
Welm, AL, Timchenko, NA, Ono, Y, Sorimachi, H, Radomska, HS, Tenen, DG, Lekstrom-Himes, J, Darlington, GJ. C/EBP is required for proteolytic cleavage of cyclin A by calpain 3 in myeloid precursor cells. J Biol Chem, 277(37);33848-56, 2002.