Gretchen Darlington, Ph.D.
Departments of Pathology, Molecular and Human Genetics, Molecular and Cellular Biology and Huffington Center on Aging
Ph.D.: University of Michigan, Ann Arbor
Postdoctoral training: Yale University, New Haven
Detoxification/Xenobiotic Metabolism in Long-Lived Mice
Our lab seeks to define the molecular basis for longevity in two different long-lived mouse strains. A single gene mutation in a pituitary-specific transcription factor (Prop-1) leads to increased longevity in mice. The growth hormone releasing hormone receptor deficient mice also result in increased longevity. By comparing the gene expression profiles of these strains with their wild type counterparts and with the other mutant strain, we have identified candidate genes for increased life span. Several pathways are implicated in the extension of lifespan and we are now pursuing the regulation of xenobiotic metabolism in the long lived strains to understand the molecular mechanisms of the up-regulation of this pathway and to determine whether the elevation of xenobiotic metabolism has a causal effect on life span.
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.
Baylor College of Medicine
One Baylor Plaza, Alkek N803
Houston, TX 77030
- Ochsner S, Strick-Marchand H, Qiu Q, Venable S, Dean A, Wilde M, Weiss M and Darlington G. (2007). Transcriptional profiling of bipotential embryonic liver cells to identify liver progenitor cell surface markers. Stem Cells Jul 26; [Epub ahead of Print].
- Amador-Noguez DA, Dean A, Huang W, Setchell K, Moore DD and Darlington GJ. (2007). Alterations in xenobiotic metabolism in the long-lived Little mice. Aging Cell Aug; 6(4):453-70.
- Bowman TV, McCooey AJ, Merchant AA, Ramos CA, Fonseca P, Poindexter A, Bradfute SB, Oliveira DM, Green R, Zheng Y, Jackson KA, Chambers SM, McKinney-Freeman SL, Norwood KG, Darlington G, Gunaratne PH, Steffen D and Goodell MA. (2006). Differential mRNA Processing in Hematopoietic Stem Cells. Stem Cells 24(3):662-70.
- Yang J, Croniger CM, Lekstrom-Himes J, Zhang P, Fenyus M, Tenen DG, Darlington GJ and Hanson RW. (2005). Metabolic response of mice to a postnatal ablation of CCAAT/enhancer-binding protein alpha. J. Biol Chem. 280(46):38689-99.
- Amador-Noquez D, Zimmerman J, Venable S and Darlington GJ. (2005). Gender-specific alterations in gene expression and loss of liver sexual dimorphism in long-lived Ames dwarf. Biochemical and Biophysical Research Communications 334(2):733-5.
- Amador-Noquez D, Yagi K, Venable S and Darlington GJ. (2004). Gene expression profile of long-lived Ames dwarf and little mice. Aging Cell Dec. 3(6):443-8.
Mackey S, Singh P and Darlington GJ. (2003). Making the Liver Young again. Hepatology 38(6):1349-52.
- Linhart HG, Ishimura-Oka K, DeMayo F, Kibe T, Repka D, Poindexter B, Bick RJ and Darlington GJ. (2001). C/EBPα is required for differentiation of white, but not brown, adipose tissue. PNAS 98:12532-7.
- Darlington GJ, Ross S and MacDougald OA. (1998). The role of C/EBP genes in adipocyte differentiation. J. Biol. Chem. 273(46):30057-30060.
Wang ND, Finegold MJ, Bradley A, Ou CN, Abdelsayed SV, Wilde MD, Taylor LR, Wilson DR and Darlington GJ. (1995). Impaired energy homeostasis in C/EBPα knockout mice. Science 269:1108-1112.