David Wassarman, PhD

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Research Description

My laboratory uses fruit flies (Drosophila melanogaster) to investigate why traumatic brain injury (TBI) is associated with increased risk of developing neurodegenerative disorders, including Alzheimer’s Disease. Using a fly TBI model of our own design, we found that the main proximal transcription response to TBI is triggered by the Toll and Imd innate immune response pathways. Additionally, we found that the risk of early mortality following TBI correlated with age at the time of injury, normal lifespan, and permeability of the intestinal barrier. Likewise, others have shown that aging in flies is associated with activation of inflammatory pathways and increased intestinal permeability as well as increased intestinal stem cell (ISC) proliferation. Based on the parallels between TBI and aging, we are investigating the cause-effect relationship between neurodegeneration due to TBI and the rate of ISC proliferation. Our data predict that the rate of ISC proliferation will correlate with the severity of TBI-induced neurodegeneration across fly lines of varied genotype and that genetic manipulation of the rate of ISC proliferation will affect the severity of TBI outcomes.

Selected References:

1. Swanson, L. C., Trujillo, E. A., Thiede, G. H., Katzenberger, R. J., Shishkova, E., Coon, J. J., Ganetzky, B., and Wassarman, D. A. (2020) Survival following traumatic brain injury in Drosophila is increased by heterozygosity for a mutation of the NF-kB innate immune response transcription factor Relish. Genetics 216, 1117-1136.
2. Swanson, L. C., Rimkus, S. A., Ganetzky, B., and Wassarman, D. A. (2020) Loss of the antimicrobial peptide Metchnikowin protects against traumatic brain injury outcomes in Drosophila melanogaster. G3 10, 3109-3119.
3. Katzenberger, R. J., Ganetzky, B., and Wassarman, D. A. (2016) Age and diet affect genetically separable injuries that cause acute mortality following traumatic brain injury in Drosophila. G3 6, 4151-4166.
4. Katzenberger, R. J., Chtarbanova, S., Rimkus, S. A., Fischer, J. A., Kaur, G., Seppala, J. M., Swanson, L. C., Zajac, J. E., Ganetzky, B., and Wassarman, D. A. (2015) Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction. eLife 2015;10.7554/eLife.04790.
5. Katzenberger, R. J., Loewen, C. A., Wassarman, D. R., Petersen, A. J., Ganetzky, B., and Wassarman, D. A. (2013) A Drosophila model of closed head traumatic brain injury. Proc. Natl. Acad. Sci. USA 110, E4152-E4159..