thummel3

Recent years have seen a dramatic rise in the incidence of diabetes and obesity worldwide, impacting all social and economic groups. The impact of these risk factors on human health has resulted in a resurgence of interest in understanding the mechanisms that underlie metabolic control. The Thummel lab uses the fruit fly, Drosophila melanogaster, as a simple genetic model to study metabolic control. Drosophila have been used for over a century to define central aspects of normal development and the causes of inherited disorders. The remarkable lesson from these studies is that many genes and pathways discovered in the fly carry over though evolution, and can be used to understand key aspects of human biology and the causes of human disease.

The goal of research in the Thummel lab is to use Drosophila as a tool to define the central pathways that control metabolism, with implications for how these pathways act in all higher animals, including humans, and how misregulation of these pathways contributes to the onset of diabetes and obesity.

Thummel lab Home Page

Research in the Thummel lab is aimed at understanding the fundamental mechanisms that control metabolism and how misregulation of metabolism can lead to disease. Metabolic regulation is central to all aspects of life, balancing energy needs with dietary input, influencing fertility, and contributing to aging. In addition, metabolic dysfunction is associated with a wide range of human disorders, including diabetes, obesity, cardiovascular disease, and some forms of cancer. Recent years have seen an alarming rise in the occurrence of diabetes and obesity in the United States, impacting all social and economic groups. Similarly, the World Health Organization has declared metabolic disorders to be a worldwide epidemic, with at least 300 million adults diagnosed as clinically obese. This increasing impact on human health has resulted in a resurgence of interest in understanding the mechanisms that underlie metabolic control, often depending on mouse models to study key metabolic disorders. Remarkably, however, relatively little has been done to exploit the power of simple genetic model systems to define the central mechanisms that coordinate metabolic responses.

The Thummel lab uses the fruit fly, Drosophila melanogaster, as a simple system to study metabolic control. Drosophila has been used for over a century to define central aspects of normal development and the causes of inherited disorders. The remarkable lesson from these studies has been that many genes and pathways discovered in the fly carry over though evolution, and can be used to understand key aspects of human biology and the causes of human disease. The goal of research in the Thummel lab is to use Drosophila as a tool to define the central pathways that control metabolism, with implications for how these pathways act in all higher animals, including humans, and how misregulation of these pathways contributes to the onset of diabetes and obesity.

Links:

Publications in PubMed

References to Publications:

Tennessen, J.M., Barry, W., Cox, J. and C.S. Thummel (2014) Methods for studying metabolism in Drosophila. Methods, 68: 105-115.

Somer, R.A. and C.S. Thummel (2014)  Epigenetic inheritance of metabolic state. Current Opinions in Genetics and Development, 27: 43-47.

Marxreiter, S. and C.S. Thummel (2014) Will branch for food – nutrient-dependent tracheal remodeling in Drosophila. EMBO J., 33: 179-180.

Van Vranken, J.G., Bricker, D.K. , Dephoure, N., Gygi, S.P., Cox, J.E., Thummel, C.S. † and J. Rutter† (2014) SHDAF4 promotes mitochondrial succinate dehydrogenase activity and prevents neurodegeneration. Cell Metabolism, 20: 241-252.

Na, U., Yu, W., Cox, J.E., Bricker, D.K., Brockmann, K., Rutter, J., Thummel, C.S. and D. Winge (2014) Two LYR assembly factors SDHAF1 and SDHAF3 mediate maturation of the iron-sulfur subunit of succinate dehydrogenase. Cell Metabolism, 20: 253-266.

Tennessen, J.M., Bertagnolli, N.M., Evans, J., Sieber, M.H., Cox, J. and C.S. Thummel (2014) Coordinated metabolic transitions during Drosophila embryogenesis and the onset of aerobic glycolysis. G3; Genes, Genomes, Genetics, 4: 839-850.

Misra, J.R., Lam, G. and C.S. Thummel (2013) Constitutive activation of the Nrf2/Keap1 pathway in insecticide-resistant strains of Drosophila. Insect Biochem. Mol. Biol., 43: 1116-1124.

Bricker, D.K., Taylor, E.B., Schell, J.C., Orsak, O., Boutron, A., Chen, Y.-C., Cox, J.E., Cardon, C.M., VanVranken, J., Dephoure, N., Redin, C., Boudina, S., Gygi, S.P., Brivet, M., Thummel, C., and J. Rutter (2012) A Mitochondrial Pyruvate Carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science, 337: 96-100 (featured in an accompanying Perspective article and highlighted by a Preview in Cell Metabolism 6(2): 141-143).

Sieber, M.H. and C.S. Thummel (2012) Coordination of triacylglycerol and cholesterol homeostasis by DHR96 and the Drosophila LipA homolog magro. Cell Metabolism, 15: 122-127.

Misra, J., Horner, M.A., Lam, G. and C.S. Thummel (2011) Transcriptional regulation of xenobiotic detoxification in Drosophila, Genes & Dev, 25: 1796-1806.

Seay, D.J. and C.S. Thummel (2011) The circadian clock, light, and cryptochrome regulate feeding and metabolism in Drosophila. J. Biol. Rhythms, 26: 497-506.

Tennessen, J.M. and C.S. Thummel (2011) Coordinating growth and maturation – insights from Drosophila. Current Biology, 21: R750-R757.

Tennessen, J.M., Baker, K.D., Lam, G., Evans, J. and C.S. Thummel (2011) ¬¬ The Drosophila Estrogen-Related Receptor directs a metabolic switch that supports developmental growth. Cell Metabolism, 13: 139-148. (featured as one of the top ten nuclear receptor papers from 2011; Mol. Endo. 25(12): 1983–1988).

Ruaud, A.-F., Lam, G. and C.S. Thummel (2011) The Drosophila NR4A nuclear receptor DHR38 regulates carbohydrate metabolism and glycogen storage. Mol. Endo, 25: 83-91.

Wang, L., Lam, G. and C.S. Thummel (2010) Med24 and Mdh2 are required for Drosophila larval salivary gland cell death. Dev. Dynamics, 239: 954-964.

Ruaud, A.-F. and C.S. Thummel (2010) The Drosophila nuclear receptors DHR3 and bFTZ-F1 control overlapping developmental responses in late embryos. Development, 137: 123-131.

Horner, M.A., Pardee, K., Liu, S., King-Jones, K., Lajoie, G., Edwards, A., Krause, H.M. and C.S. Thummel (2009) The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis. Genes & Dev., 23: 2711-2716.

Sieber, M. and C.S. Thummel (2009) The DHR96 nuclear receptor controls triacylglycerol homeostasis in Drosophila. Cell Metabolism, 10: 481-490 (cover article, featured in an accompanying Preview article, featured in the monthly Cell Press podcast).

Palanker, L., Tennessen, J.M., Lam, G. and C.S. Thummel (2009) Drosophila HNF4 regulates lipid mobilization and b-oxidation. Cell Metabolism, 9: 228-239 (highlighted in Nature Chemical Biology, May 2009, 5:281).

Kozlova, T., Lam, G. and C.S. Thummel (2009) The Drosophila DHR38 nuclear receptor is required for adult cuticle integrity at eclosion. Dev. Dynamics, 238: 701-707.

Wang, L., Evans, J., Andrews, H.K., Beckstead, R.B., Thummel, C.S. and A. Bashirullah (2008) A genetic screen identifies new regulators of steroid-triggered programmed cell death in Drosophila. Genetics, 180: 269-281.

McBrayer, Z., Ono, H., Shimell, M.J., Parvy, J.-P., Beckstead, R.B., Warren, J.T., Thummel, C.S., Dauphin-Villemant, C., Gilbert, L.I., and M.B. O’Connor (2007) Prothoracicotropic hormone regulates developmental timing and body size in Drosophila. Dev. Cell, 13: 857-871.

osis. Dev. Dynamics, 236: 3173-3179 (a highlighted article in Dev. Dynamics).

Baker, K.D. and C.S. Thummel (2007) Diabetic larvae and obese flies – emerging studies of metabolism in Drosophila. Cell Metabolism, 6: 257-266.

Yin, V.P., Thummel, C.S. and A. Bashirullah (2007) Down-regulation of Inhibitor of Apoptosis (IAP) levels provides competence for steroid-triggered cell death, J. Cell Biology, 178: 85-92 (one of five highlighted articles in that issue).

Beckstead, R.B., Lam, G., and C.S. Thummel (2007) Specific transcriptional responses to juvenile hormone and ecdysone in Drosophila, Insect Biochem. Mol. Biol., 37: 570-578.

C.S. Thummel (2007) To die or not to die – A role for Forkhead. J. Cell Biol., 176: 737-739.

Baker, K.D., Beckstead, R.B., Mangelsdorf, D.J. and C.S. Thummel (2007) Functional interactions between the Moses corepressor and DHR78 nuclear receptor regulate growth in Drosophila, Genes & Dev, 21: 450-464.

Palanker, L., Necakov, A.S., Sampson, H.M., Ni, R., Hu, C., Thummel, C.S., and H.M. Krause (2006) Dynamic regulation of Drosophila nuclear receptor activity in vivo. Development, 133: 3549-3562.

King-Jones, K., Horner, M.A., Lam, G. and C.S. Thummel (2006) The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila. Cell Metabolism, 4: 37-48.

Beckstead, R.B. and C.S. Thummel (2006) Indicted – C. elegans caught using steroids. Cell, 124: 1137-1140.

King-Jones, K. and C.S. Thummel (2005) Less steroids make bigger flies. Science, 310: 630-631.

Beckstead, R.B., Lam, G., and C.S. Thummel (2005) The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis. Genome Biology, 6: R99.

C.S. Thummel (2005) Powered by gas – a ligand for a fruit fly nuclear receptor. Cell, 122: 151-153.

King-Jones, K., Charles, J.-P., Lam, G. and C.S. Thummel (2005) The ecdysone-induced DHR4 orphan nuclear receptor coordinates growth and maturation in Drosophila. Cell, 121: 773-784.

Yin, V.P. and C.S. Thummel (2005) Mechanisms of steroid-triggered programmed cell death in Drosophila. Sem. in Cell and Dev. Biol., 16: 237-243.

King-Jones, K. and C.S. Thummel (2005) Nuclear receptors – a perspective from Drosophila. Nature Reviews Genetics, 6: 311-323.

Yin, V.P. and C.S. Thummel (2004) A balance between the diap1 death inhibitor and reaper and hid death inducers controls steroid-triggered cell death in Drosophila. Proc. Natl. Acad. Sci. USA, 101: 8022-8027.

Gates, J., Lam, G., Ortiz, J.A., Losson, R., and C.S. Thummel (2004) rigor mortis encodes a novel nuclear receptor interacting protein required for ecdysone signaling during Drosophila larval development. Development, 131: 25-36.

Address

Department of Human Genetics
University of Utah School of Medicine
15 N 2030 E RM 2100
Salt Lake City, Utah 84112-5330

Phone

801-581-2937

Fax

801-581-5374