Denise Ferkey

PhD

Denise Ferkey.

Denise Ferkey

PhD

Denise Ferkey

PhD

Research Interests

C. elegans sensory biology: G protein-coupled signal transduction and regulation

Education

  • BS, Saint Norbert College
  • PhD, University of Washington
  • Postdoctoral Research, Massachusetts General Hospital Cancer Center and Harvard Medical School

Research Summary

We use C. elegans sensory behavior (e.g. chemosensation) as a model to understand the interconnected mechanisms and regulatory pathways used by nerve cells to modulate signaling and ultimately control animal behavior. Areas of focus include: understanding how cGMP levels change in response to an animal’s feeding status and how cGMP moves through a gap junction neural circuit to modulate behavioral sensitivity to aversive stimuli; exploring the mechanisms by which the neurotransmitter dopamine modulates signaling and behavior; investigating how post-translational modification of G protein-coupled receptors (GPCRs) by arginine methylation regulates their function; and exploring how natural variation in chemosensory behavior is encoded and evolves at the molecular level.

Science Signaling.

The laboratories of Dr. Denise Ferkey and Dr. Michael Yu collaborated to provide the first direct evidence that GPCRs are functionally regulated by arginine methylation, focusing first on D2-like dopamine receptors. As reported in Science Signaling these GPCRs served as the founding members of a new class of proteins that are functionally regulated by arginine methylation. Their subsequent work has shown that additional GPCRs are also regulated by arginine methylation, delineating a new means of regulating G protein-coupled signal transduction. These findings have strong potential to influence the development of a new generation of treatments based on manipulating GPCR methylation status – not only for D2-linked neuropsychiatric disorders, but also for the treatment of diseases ranging from cancer to chronic heart failure.

Funding Support
Ellison Medical Foundation
National Science Foundation
National Institutes of Health

Selected Publications

  • Hart, P., Bowitch, A., Mellmann, A., Ferkey, D.M. and Koudelka, G.B. (2026) Factors Governing the Cross-Species Virulence of Shiga Toxin-Producing Escherichia coliPathogens. 15(4):353. Article.
  • Polk, E.A., Aquil, A., Collins, J.B., Tanny, R.E., Andersen, E.C., Gokcumen, O. and Ferkey, D.M. (2025) Wild strains reveal natural variation in C. elegans avoidance behaviors. G3: Genes, Genomes, Genetics. 15(12), jkaf243. Article.
  • Sojka, S.E., Ezak, M.J., Polk, E.A., Bischer, A.P., Nehland, K.E., Wojtovich, A.P. and Ferkey, D.M. (2025) An extensive gap junction neural network modulates Caenorhabditis elegans aversive behavior. Genes. 16(3):260. Article.
  • Chaubey, A.H., Sojka, S.E., Onukwufor, J.O., Ezak, M.J., Vandermeulen, M.D., Bowitch, A., Vodičková, A., Wojtovich, A.P. and Ferkey, D.M. (2023) The Caenorhabditis elegans innexin INX-20 regulates nociceptive behavioral sensitivity. Genetics. 223(4):iyad017. Article.
  • Pechuk, V., Goldman, G., Salzberg, Y., Chaubey, A.H., Bola, R.A., Hoffman, J.R., Endreson, M.L., Miller, R.M., Reger, N.J., Portman, D.S., Ferkey, D.M., Schneidman, E. and Oren-Suissa, M. (2022) Reprogramming the topology of the nociceptive circuit in C. elegans reshapes sexual behavior. Current Biology. 32(20):4372-4385. Article.
  • Berghoff, E.G., Glenwinkel, L., Bhattashaya, A., Sun, H., Varol, E., Mohammadi, N., Antone, A., Feng, Y., Nguyen, K., Cooke, S., Wood, J.F., Masoudi, N., Cross, C.C., Ramadan, Y.H., Ferkey, D.M., Hall, D.H. and Hobert, O. (2021) The Prop1-type homeobox gene unc-42 specifies the identity of synaptically connected neurons. eLife. 10:e64903. Article.
  • Ferkey, D.M., Sengupta, P. and L'Etoile, N.D. (2021) Chemosensory signal transduction in Caenorhabditis elegansGenetics. 217(3):iyab004. Article.
  • Voelker, L., Upadhyaha, B., Ferkey, D.M., Woldemariam, S., L’Etoile, N.D., Rabinowitch and Bai, J. (2019) INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in C. elegansPLoS Genetics. 15(10):e100834.  Article.
  • Woldemariam, S., Nagpal, J., Hill, T., Li, J., Schneider, M.W., Shankar, R., Futey, M., Varshney, A., Ali, N., Mitchell, J., Andersen, K., Barsi-Rhyne, B., Tran, A., Steuer Costa, W., Krzyzanowski, M.C., Yu, Y.V., Brueggemann, C., Hamilton, O.S., Ferkey, D.M., VanHoen, M., Sengupta, P., Gottschalk, A. and L'Etoile, N.D. (2019) Robust and sensitive GFP-based cGMP sensor for real time imaging in intact C. elegansGenetics. 213(1):59-77. Article.
  • Chow J., Starr, I., Jamalzadeh, S., Muniz, O., Kumar, A., Gokcumen, O., Ferkey, D.M. and Cullen, P.J. (2019) Filamentation regulatory pathways control adhesion-dependent surface responses in yeast. Genetics.  212(3):667-690. Article. 
  • Bowitch, A., Michaels, K.L., Yu, M.C. and Ferkey, D.M. (2018) The protein arginine methyltransferase PRMT-5 regulates SER-2 tyramine receptor-mediated behaviors in C. elegans. G3: Genes, Genomes, Genetics. 8(7):2389-2398. Article.
  • Krzyzanowski, M.C., Woldemariam, S., Wood, J.F., Chaubey, A.H., Brueggemann, C., Bowitch, A., Bethke, M., L’Etoile, N.D. and Ferkey, D.M. (2016) Aversive behavior in the nematode C. elegans is modulated by cGMP and a neuronal gap junction network. PLoS Genetics. 12(7):e1006153. Article.
  • Likhite, N., Jackson, C.A., Liang, M-S., Krzyzanowski, M.C., Lei, P., Wood, J.F., Birkaya, B., Michaels, K.L., Andreadis, S.T., Clark, S.D., Yu, M.C. and Ferkey, D.M. (2015) The protein arginine methyltransferase PRMT5 promotes D2-like dopamine receptor signaling. Science Signaling. 8(402):ra115.  Article.
  • Krzyzanowski, M.C., Brueggemann, C., Ezak, M.J., Wood, J.F., Michaels, K.L., Jackson, C.A., Juang, B-T., Collins, K., Yu, M.C., L’Etoile, N.D. and Ferkey, D.M. (2013) The C. elegans cGMP-dependent protein kinase G EGL-4 regulates nociceptive behavioral sensitivity. PLoS Genetics.  9(7):e1003619. Article.
  • Mann, J.K., Wood, J.F., Stephan, A.F., Tzanakakis, E.S., Ferkey, D.M. and Park, S. (2013) Epitope-guided engineering of monobody binders for in vivo inhibition of Erk-2 signaling. ACS Chemical Biology. 8(3):608-616. Article.
  • Wood, J.F., Wang, J., Benovic, J.L. and Ferkey, D.M.  (2012)  Structural domains required for C. elegans G protein-coupled receptor kinase 2 (GRK-2) function in vivo. Journal of Biological Chemistry. 287(16):12634-12644. Article.
  • Ezak, M.J. and Ferkey, D.M. (2011) A functional nuclear localization sequence in the C. elegans TRPV channel OCR-2. PLoS ONE. 6(9):e25047.  Article.
  • Huang, H., Delikanli, S., Zeng, H., Ferkey, D.M. and Pralle, A. (2010) Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. Nature Nanotechnology. 5(8):602-606. Article.
  • Ezak, M.J., Hong, E., Chaparro-Garcia, A. and Ferkey, D.M. (2010) C. elegans TRPV channels function in a modality-specific pathway to regulate response to aberrant sensory signaling. Genetics. 185(1):233-244. Article.
  • Ezak, M.J. and Ferkey, D.M. (2010) The C. elegans D2-like dopamine receptor DOP-3 decreases sensitivity to the olfactory stimulus 1-octanol. PLoS ONE.  5(3):e9487. Article.
  • Ferkey, D.M., Hyde, R., Haspel, G., Dionne, H.M., Hess, H.A., Suzuki, H., Schafer, W.R., Koelle, M.R. and Hart, A.C.  (2007) C. elegans G protein regulator RGS-3 controls sensitivity to sensory stimuli. Neuron. 53(1):39-52. Article.
  • Fukuto, H.S., Ferkey, D.M., Apicella, A.J., Lans, H., Sharmeen, T., Chen, W., Lefkowitz, R.J., Jansen, G., Schafer, W.R., and Hart, A.C. (2004) G protein-coupled receptor kinase function is essential for chemosensation in C. elegans. Neuron. 42(4):581-593. Article.