|Area of Study:
||Cell Biology, Developmental Biology
||East Carolina University
|Department of Biology;
|Greenville, NC 27858
B.S., St. Andrews Presbyterian College, 1999
M.S., University of North Carolina at Wilmington, 2001
Ph.D., Vanderbilt University, 2007
Post-Doctoral Training, Johns Hopkins University School of Public Health, 2012
My research seeks to understand a fundamental question in stem cell biology:how do adult stem cells sense and respond to changes in whole-body physiology?To meet changing physiological demand, stem cells are particularly dependent upon organismal nutrient sensing systems to balance their unique properties of self-renewal and the production of specialized progeny, allowing for the replacement of cells lost by attrition, regeneration, repair, or remodeling.Stem cell proliferation rates and maintenance of stem cell population size are therefore tightly controlled by the integration of signals from the local environment (or niche) and systemic signals, such as steroid hormones, which fluctuate in response to nutrient intake and other physiological inputs. While many studies have investigated the regulation of stem cells by local signaling pathways, we are only beginning to ascertain the impact of systemic signals on stem cell function.The Drosophila melanogaster ovary, a well-described stem cell-based tissue that responds to external stimuli, is a powerful model system to study the molecular mechanisms controlling stem cell activity in vivo.My long-term research goal is to understand how steroid hormone signaling regulates adult stem cell activity in response to changes in physiological demand.Using well-characterized stem cell populations in Drosophila as models, I will utilize genetic and cell biological approaches to assess in vivo the pivotal role of steroid hormones and their receptors in controlling tissue-specific stem cell behavior.
In my post-doctoral research, I found that ecdysone, a systemic steroid hormone produced by more mature follicles under nutrient-rich conditions, directly controls GSC proliferation and maintenance. Ecdysone, one of a group of related ecdysteroids, elicits transcriptional responses primarily by activating a heterodimeric receptor complex consisting of two nuclear hormone receptors (NHRs), Ecdysone Receptor (EcR) and Ultraspiracle (USP).Using global mutants and Flippase (FLP)/FLP recognition target (FRT)-mediated genetic mosaics (for temporally-specific pathway inactivation) to reduce ecdysone levels or signaling, I showed that GSCs directly require ecdysone signaling for proper rates of proliferation.Further, I found that E74, a transcription factor that is rapidly induced in response to ecdysone in larval tissues, is a key downstream target of EcR/USP activation in stem cells, as E74-deficient GSCs fail to proliferate, similar to usp-deficient GSCs.Interestingly, ecdysone signaling, similar to other nutritional inputs, appears to control GSC proliferation by acting on the G2 phase of the cell cycle:I am currently investigating whether non-canonical cyclin E expression during G2 may underlie this regulation.I also showed that flies with global reductions in ecdysone levels or signaling rapidly lose GSCs from the niche.Using genetic mosaic analysis, I found that the ecdysone signal is directly required for GSC maintenance, and is likely transduced, in part, via E74.Myresults suggest that long-range ecdysone signals act in concert with both intrinsic factors and local signals to promote GSC self-renewal.
As a new investigator, my research will seek to understand how steroid hormone signaling downstream of ecdysone signaling, or in parallel to ecdysone signaling, coordinates stem cell activity with the physiological status of the organism.I will use a combination of genetic and molecular biological approaches to address the following questions:
What targets of ecdysone signaling mediate GSC proliferation and maintenance?
Do the different EcR isoforms mediate regulation of different transcriptional targets?
Do other nuclear hormone receptors regulate stem cell activity independent of EcR signaling?
Cyclin E controls Drosophila female germline stem cell maintenance independently of its role in proliferation by modulating responsiveness to niche signals. E. T. Ables and D. Drummond-Barbosa (submitted, 2012).
In vivocontrol of adult stem cells by a dynamic physiological environment: diet-dependent systemic factors in Drosophila and beyond. E. T. Ables, K. M. Laws, and D. Drummond-Barbosa. Wiley Interdisciplinary Reviews Developmental Biology (2012), 1: 657-674, doi: 10.1002/wdev.48.
Food for thought:neural stem cells on a diet. E. T. Ables and D. Drummond-Barbosa. Cell Stem Cell (2011), 8 (4):352.
The steroid hormone ecdysone functions with intrinsic chromatin remodeling factors to control female germline stem cells in Drosophila. E. T. Ables and D. Drummond-Barbosa. Cell Stem Cell (2010), 7 (5):581.
Multiple, temporal-specific roles for HNF6 in pancreatic endocrine and ductal differentiation. H. Zhang*, E. T. Ables*, C. F. Pope, M. K. Washington, S. Hipkens, A. Means, G. Path, J. Seufert, R. H. Costa, A. B. Leiter, M. A. Magnuson, and M. Gannon.Mechanisms of Development (2009), 126 (11-12):958. *Both authors contributed equally to this work.
Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis. L. W. Crawford,* E. T. Ables*, Y. A. Oh, B. Boone, S. Levy, and M. Gannon. Public Library of Science ONE (2008), 3 (2):e1161. *Both authors contributed equally to this work.
pdx1function is specifically required in embryonic cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. M. Gannon, E. T. Ables, L. Crawford, D. Lowe, M. F. Offield, M. A. Magnuson, and C. V. E. Wright. Developmental Biology (2008), 314 (2):406.
Maintenance of Hnf6 in postnatal islets impairs terminal differentiation and function of cells. E. Tweedie**, I. Artner, L. Crawford, G. Poffenberger, B. Thorens, R. Stein, A. C. Powers, and M. Gannon.Diabetes (2006), 55 (12):3264. **Ables maiden name.
Purification of a soluble glycoprotein from the uncalcified ecdysial cuticle of the blue crab Callinectes sapidus and its possible role in initial mineralization. E. P. Tweedie**, F. E. Coblentz, and T. H. Shafer. Journal of Experimental Biology (2004), 207 (Pt 15):2589. **Ables maiden name.
My lab will be accepting motivated students, eager to learn research skills in genetics, molecular biology, and microscopy, effective Summer 2013.If you are interested in obtaining undergraduate research experience or in pursuing graduate education in the Biology Department, please contact me via email to discuss available opportunities.