Biology Department

Research Summary

Stem Cells, Metabolism and Aging.

We are interested in regulatory mechanisms that control stress tolerance, metabolism and aging in multi-cellular organisms. Current projects in the lab focus on the control of metabolic homeostasis, cell death and tissue regeneration by insulin and stress signaling pathways. We perform these studies in Drosophila melanogaster, taking advantage of the wide range of genetic, molecular, and genomic techniques available for this model organism.

Our current work focuses on signaling mechanisms that influence the following physiological processes with relevance to aging:

• Signaling networks controlling growth and metabolic homeostasis

Lifespan and metabolic homeostasis are regulated by endocrine interactions between insulin producing and insulin target tissues. Insulin producing cells (IPCs) and adipose tissue play a major role in this regulatory network. Stress signaling, in particular the Jun-N-terminal Kinase (JNK) pathway, has been shown to influence insulin-like peptide production in IPCs, but also to cause insulin resistance in insulin target tissues. Our work aims at establishing how stress signaling interacts with insulin signaling to control metabolic homeostasis, thus influencing lifespan, stress and starvation tolerance.

• Stress-induced cell death

In response to DNA damage, cells have to decide whether to survive and repair the damage or whether to undergo programmed cell death (apoptosis). Activation of JNK signaling can promote cyto-protective gene expression, but can also induce cell death. We use the developing Drosophila retina as a model system in which to assess the genetic regulation of this decision between survival and death in response to JNK signaling.

• Regeneration

Regenerative processes are important for long-term tissue homeostasis in metazoans. Pluripotent stem cells, which have the ability to self-renew, while producing cell progeny that can differentiate into various specialized cell types, are central to such regenerative processes. We are studying stem cells in the Drosophila midgut epithelium to ask how stress and aging influences their ability to self-renew, and whether optimizing stem cell activity can influence the aging process in metazoans.

Publications

1. Jasper H, Benes V, Schwager C, Sauer S, Clauder-Muenster S, Ansorge W, Bohmann D. 2001. The genomic response of the Drosophila Embryo to JNK signaling. Dev Cell 1: 579-86. PMID: 11703947
2. Jasper H, Benes V, Atzberger A, Sauer S, Ansorge W, Bohmann D. 2002. A genomic switch at the transition from cell proliferation to terminal differentiation in the Drosophila eye. Developmental Cell 3: 511-21. PMID: 12408803
3. Jasper H, Bohmann D. 2002. Drosophila innate immunity: a genomic view of pathogen defense. Mol Cell 10: 967-9. PMID: 12453405
4. Wang MC, Bohmann D, Jasper H. 2003. JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila.. Dev Cell 5: 811-6. PMID: 14602080
5. Wang MC, Bohmann D, Jasper H. 2005. JNK extends lifespan and limits growth by antagonizing cellular and organism-wide responses to Insulin signaling. Cell 121: 115-25. PMID: 15820683
6. Uhlirova, M, Jasper H, Bohmann, D. 2005. Non Cell-Autonomous Induction of Tissue Overgrowth by JNK/Ras Cooperation in a Drosophila Tumor Model. Proceedings of the National Academy of Sciences 102: 13123-8. PMCID: PMC1201591
7. Jasper H. 2005. Using SAGE to analyze signaling and development in Drosophila. SAGE: Current Technologies and Applications Wang, S.M., editor. Horizon Scientific Press, Norfolk, UK.
8. Hyun J, Jasper H, Bohmann D. 2005. DREF is required for efficient growth and cell cycle progression in Drosophila imaginal discs. Mol Cell Biol 25: 5590-8. PMCID: PMC1157005
9. Homsy JG, Jasper H, Peralta XG, Wu H, Kiehart DP, Bohmann D. 2006. JNK signaling coordinates integrin and actin functions during Drosophila embryogenesis. Dev Dyn 235: 427-34.
10. Jasper H. 2006. Migration in action: profiling border cells. Dev Cell 10: 414-5.
11. Luo, X., Puig, O., Hyun, J., Bohmann, D. & Jasper, H. 2007. Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation. EMBO Journal 26: 380-90. PMCID: PMC1783446
12. Jasper H. 2008. SKNy worms and long life. Cell 132: 915-6. PMC Exempt: Accepted before April 8, 2008.
13. Damgaard-Nielsen, M., Luo, X., Biteau, B., Syverson, K., Jasper, H. 2008. 14-3-3epsilon antagonizes Foxo to control growth, stress tolerance and longevity in Drosophila. Aging Cell 7: 688-99. PMCID in process. PMID: 18665908
14. Biteau, B., Hochmuth, C.E., Jasper, H. 2008. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3: 442-55. PMCID: PMC Journal - in process. PMID: 18940735
15. Hull-Thompson, J., Muffat, J., Sanchez, D., Walker, D., Benzer, S., Ganfornina, M.D., Jasper, H. 2009. Control of metabolic homeostasis by stress signaling is mediated by the Lipocalin NLaz. PLoS Genet 5: e1000460. Epub Apr 24. PMCID: PMC2667264
16. Karpac, J., Jasper, H. 2009. Insulin and JNK: optimizing metabolic homeostasis and lifespan. Trends Endocrinol Metab 20: 100-6. PMCID in process.
17. Karpac, J., Hull-Thompson, J., Falleur, M., Jasper, H. 2009. JNK signaling in insulin-producing cells is required for adaptive responses to stress in Drosophila. Aging Cell 8: 288-95. PMCID: PMC2727449
18. Biteau, B., Karpac, J., Supoyo, S., DeGennaro, M., Lehmann, R., Jasper, H. 2010. Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet 6: e1001159. PMCID: PMC2954830
19. Biteau B., Karpac J., Hwangbo D., Jasper H. 2010. Regulation of Drosophila lifespan by JNK signaling. Exp Gerontol 46: 349-54. PMCID: PMC3079798
20. Jasper, H., Jones, D.L. 2010. Metabolic regulation of stem cell behavior and implications for aging. Cell Metab 12: 561-5. PMCID: PMC3012644
21. DeGennaro, M., Hurd, T.R., Siekhaus, D.E., Biteau, B., Jasper, H., Lehmann, R. 2011. Peroxiredoxin stabilization of DE-Cadherin promotes primordial germ cell adhesion. Dev Cell 20: 233-43. PMC Journal - in process.
22. Karpac, J., Younger, A., Jasper, H. 2011. Dynamic coordination of innate immune signaling and Insulin signaling regulates systemic responses to localized DNA damage. Dev Cell 20: 841-54. PMCID: PMC3151532
23. Biteau, B., Jasper, H. 2011. EGF signaling regulates the proliferation of intestinal stem cells in Drosophila. Development 138: 1045-55. PMCID: PMC3042864
24. Hochmuth, C., Biteau, B., Bohmann, D., Jasper, H. 2011. Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila. Cell Stem Cell 8: 188-99. PMCID: PMC3035938
25. Karpac, J., Jasper, H. 2011. Metabolic homeostasis: HDACs take center stage. Cell 145: 497-9. PMC Journal - in process.
26. Biteau, B., Hochmuth, C.E., Jasper, H. 2011. Maintaining tissue homeostasis: Dynamic control of somatic stem cell activity. Cell Stem Cell 9: 402-11. PMC in process.