Faculty & Research
- Contact Information
- Contact Jason Tennessen by jtenness [at] indiana [dot] edu
- By telephone: 855-9803 / 856-3616 (lab)
- JH 343B / JH 341 (lab)
- Genome, Cell & Developmental Biology
- Research Area
- Developmental Mechanisms and Regulation in Eukaryotic Systems
Postdoctoral Fellow, University of Utah, 2007-2013
Ph.D., University of Minnesota, 2007
B.A., Lawrence University, 2001
NIH K99/R00 Pathway to Independence Award (NIGMS), 2011-2016
NIH R35 Maximizing Investigators' Research Award for Early Stage Investigators (NIGMS), 2016-2021
Both cancer cells and embryonic stem cells rely on a specialized metabolic program known as aerobic glycolysis to support their rapid proliferation. Aerobic glycolysis, which is also known as the Warburg effect in the context of tumor metabolism, is characterized by the increased expression of glucose transporters, enzymes involved in glycolysis, and other proteins that promote glycolytic flux. This up-regulation of glycolysis, however, is not solely used to produce energy. Instead, the abundant supply of glucose-derived metabolites is used to generate the amino acids, nucleotides, and fatty acids required for rapid proliferation. Meanwhile, a significant quantity of the pyruvate generated during this process is not oxidized in the mitochondria, but rather is converted into lactate—a hallmark of aerobic glycolysis that is required for maximal glycolytic flux.
The manner in which rapid cell proliferation relies on aerobic glycolysis suggests that understanding the molecular mechanisms regulating this metabolic program could lead to new cancer therapies, as well as advances in the field of stem cell biology. Toward this goal, several groups are using mammalian cell culture to study aerobic glycolysis. There is still a significant need, however, for model systems with which to explore how cells initiate aerobic glycolysis in vivo. In order to fill this void, my lab is using the fruit fly Drosophila melanogaster as a genetic model to study aerobic glycolysis.
All growth during the Drosophila life cycle is restricted to the larval stage, when animals increase their body size approximately 200-fold over the course of four days. This growth phase is preceded by a dramatic metabolic switch, which induces the coordinate expression of nearly every gene involved in glycolysis and lactate production. The resulting metabolic program displays the central hallmarks of aerobic glycolysis, indicating that like cancer cells, growing larvae use this metabolic program to efficiently derive biomass from carbohydrates. My lab is exploiting this discovery to determine how aerobic glycolysis is regulated in the context of normal animal growth and physiology. Our current research is focused on three major areas:
Molecular mechanisms that regulate the onset of aerobic glycolysis
Unlike cancer cells, the onset of aerobic glycolysis in Drosophila occurs at a highly reproducible timepoint, approximately 12 hours prior to the beginning of larval growth. The predictability of Drosophila development, therefore, provides a unique opportunity to determine how changes in gene expression and metabolite abundance affect the onset of aerobic glycolysis. We are using a combination of metabolomics, genomics, and genetics to identify the factors that promote aerobic glycolysis. As part of these efforts, my lab is characterizing the Drosophila Estrogen-Related Receptor (dERR), the sole ortholog of the mammalian ERR nuclear receptor family. dERR activates aerobic glycolysis in preparation for larval growth, a role which is conserved in cancer cell lines, suggesting that our studies in the fly could reveal novel regulators of cancer cells metabolism.
Factors that repress aerobic glycolysis
The metabolic program activated in preparation for larval development is terminated upon the completion of growth, when a precipitous drop in glycolytic gene expression signals the coordinate inhibition of aerobic glycolysis. This late larval metabolic transition places Drosophila larval development in stark contrast with cancer cells, where aerobic glycolysis is indefinitely activated, and provides a unique opportunity to identify the mechanisms that repress aerobic glycolysis in vivo. My lab is studying the developmental events that inhibit aerobic glycolysis with the goal of finding metabolic regulators that could be used to clinically interfere with tumor metabolism.
Targeted disruption of aerobic glycolysis
Studies in cancer cell lines suggest that the targeted inhibition of aerobic glycolysis could effectively slow tumor growth. This cell culture approach, however, does not necessarily predict the efficacy of similar treatments in vivo. We are inhibiting specific enzymes involved in aerobic glycolysis to determine how the disruption of this metabolic program affects tissue growth in the context of Drosophila development.
Tennessen JM, Barry W, Cox J, and Thummel CS. (2014). Methods for studying metabolism in Drosophila. Methods. 68(1):105-115. [Invited review for a special issue on Drosophila methods].
Tennessen JM, Bertagnolli NM, Evans J, Sieber MH, Cox J, and Thummel CS. (2014). Coordinate metabolic transitions during Drosophila embryogenesis and the onset of aerobic glycolysis. G3:Genes|Genomes|Genetics. 4(5):839-50
- Bertagnolli NM, Drake JA, Tennessen JM, and Alter O. (2013) SVD Identifies Transcript Length Distribution Functions from DNA Microarray Data and Reveals Evolutionary Forces Globally Affecting GBM Metabolism. PLoS One. 8 (11): e78913
Tennessen JM, Baker KD, Lam G, Evans J, and Thummel CS. (2011). The Drosophila Estrogen-Related Receptor directs a metabolic switch that supports developmental growth. Cell Metabolism. 13:139-48.
- Tennessen JM and Thummel CS. (2011). Coordinating growth and maturation – insights from Drosophila. Current Biology. 21:R750-R757.
Tennessen JM, Opperman KJ, and Rougvie AE. (2010). The C. elegans developmental timing protein LIN-42 regulates diapause in response to environmental cues. Development. 137:3501-11.
Palanker L, Tennessen JM, Lam G, Thummel CS. (2009). Drosophila HNF4 regulates lipid mobilization and beta-oxidation. Cell Metabolism. 9:228-39.
Tennessen JM and Thummel CS. (2008). let-7: Developmental timing conserved through evolution. Current Biology. 18: R707-708.