The research in my lab is focused on the plasticity of neuroendocrine signaling, with special attention to neuropeptide and peptide hormone (peptidergic) systems and their roles in animal behavior.

Neuropeptides are small polypeptides or proteins that are released by nerve cells to affect the development or activity of other cells. Acting as modulators of nerve cell signaling and as hormones, neuropeptides are central regulators of diverse processes, including growth, reproduction, stress, energy balance, and sleep. A fundamental characteristic of these systems is their inherent flexibility (plasticity). Organisms alter cellular neuropeptide levels dramatically in response to internal and external cues. The resulting changes in the strength of neuropeptide signaling are an essential feature of the neuroendocrine and physiological feedback loops that establish and regulate many homeostatic mechanisms. This form of regulation has been intensively studied in a few amenable systems, and contributions of a few signals such as steroids to changes in neuropeptide gene expression are well documented.Nevertheless, in many systems, the heterogeneity of peptidergic tissues has limited progress toward a general molecular understanding of the mechanisms governing neuroendocrine cell plasticity.

We are tackling this problem in a model genetic system, the fruit fly (Drosophila melanogaster), where novel features of molecular pathways can be isolated and readily studied, and where we can take full advantage of a powerful and unparalleled set of methods and gene mutations for the analysis of peptidergic cells. For example, we can monitor movements of fluorescent neuropeptides in living tissue, we can target genetic mutations to small groups of peptidergic cells, we can perform these cell-specific genetic manipulations at specific times in the life cycle of the animal, and we can easily detect external defects that result from disruptions in the development or function of peptidergic cells and in the behaviors that they control, even days after the behaviors normally occur. We are currently using all of these tools in our research.

Our current research interests include:

• Development and plasticity of peptidergic cells controlling ecdysis and wing expansion behavior.
• Regulation of ecdysis-triggering hormone expression by steroids and the CRC basic-leucine zipper transcription factor.
• Live-cell imaging of basic cellular mechanisms underlying neuropeptide and peptide hormone secretion.

• Gu, T., Zhao, T., Kohli, U. & Hewes, R.S. (2017).  The large and small SPEN family proteins stimulate axon outgrowth during neurosecretory cell remodeling in Drosophila. Developmental Biology 431(2):226-238 (link)

• Chen, D., T. Gu, T.N. Pham, M.J. Zachary, & R.S. Hewes (2017).  Regulatory mechanisms of metamorphic neuronal remodeling revealed through a genome-wide modifier screen in Drosophila. Genetics, 206(3):1429-1443. (link)

• D. Chen, Qu, C., Bjorum, S.M., Beckingham, K.M.,  & Hewes, R.S. (2014). Neuronal remodeling during metamorphosis is regulated by the alan shepard (shep) gene in Drosophila melanogaster. Genetics 197(4):1267-1283. (link) (journal highlight)
   
• Bulgari, D., Zhou, C., Hewes, R.S., Deitcher, D.L., & Levitan, E.S. (2014) Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals. PNAS 111(9)3597-3601. (link)
   
• Gu, T., T. Zhao, & R.S. Hewes.(2014) Insulin signaling regulates neurite growth during metamorphic neuronal remodeling. Biology Open 3(1):81-93. (open access)
   
• Gauthier, S.A., VanHaaften, E., Cherbas, L., Cherbas, P., and Hewes, R.S. (2012). Cryptocephal, the Drosophila melanogaster ATF4, Is a Specific Coactivator for Ecdysone Receptor Isoform B2. PLoS Genetics 8(8):1-8. (open access)
   
• Shakiryanova, D., Zettel, G., Gu, T., Hewes, R.S., & Levitan, E.S. (2011). Synaptic neuropeptide release induced by octopamine without Ca2+ entry into the nerve terminal. PNAS 108(11):4477-4481. (open access) 
   
• Hewes, R.S. (2008).  The buzz on fly neuronal remodeling.  TRENDS in Endocrinology and Metabolism 19(9):317-323. (link)
   
• Zhao, T., Gu, T., Rice, H.C., McAdams, K.L., Roark, K.M., Lawson, K., Gauthier, S.A., Reagan, K.L., and Hewes, R.S. (2008). A Drosophila gain-of-function screen for candidate genes controlling steroid-dependent neuroendocrine cell remodeling. Genetics 178(2):883-901. (open access) 
   
• Shakiryanova, D., Klose, M., Zhou, Y., Gu, T., Deitcher, D.L., Atwood, H.L., Hewes, R.S. and Levitan, E.S. (2007). Presynaptic ryanodine receptor-activated calmodulin kinase II increases vesicle mobility and potentiates neuropeptide release. Journal of Neuroscience 27(29):7799-7806. (open access) 
   
• Hewes, R.S., Gu, T., Brewster, J.A., Qu, C. & Zhao, T. (2006). Regulation of secretory protein expression in mature cells by DIMM, a bHLH neuroendocrine differentiation factor. Journal of Neuroscience 26(30):7860-7869. (open access) 
   
• Gauthier, S.A., and Hewes, R.S. (2006). Transcriptional regulation of neuropeptide and peptide hormone expression by the Drosophila dimmed and cryptocephal genes. Journal of Experimental Biology 209(10):1803-1815 (and cover photo). Featured in the column, Inside JEB [K Phillips (2006). DIMM Regulates Neuropeptide Levels. J. Exp. Biol. 209(10):i-a]. (open access) (journal highlight)
  
  
• Shakiryanova, D., Tully, A., Hewes, R.S., Deitcher, D.L. & Levitan, E.S. (2005). Activity-dependent liberation of synaptic neuropeptide vesicles. Nature Neuroscience 8(2):173-178. (link) Faculty of 1000 rating: 3.0.