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

Our research is directed towards understanding the regulatory mechanisms that control animal behavior. Using C. elegans sensory behavior (e.g. chemosensation) as a model, we study the regulation of G protein-coupled signal transduction pathways as well as the mechanisms by which the neurotransmitter dopamine modulates signaling and behavior.

A study published in Science Signaling by the laboratories of Dr. Denise Ferkey and Dr. Michael Yu provides the first direct evidence that G protein-coupled receptors (GPCRs) are functionally regulated by arginine methylation. Specifically, they show that arginines within the third intracellular loop of the human D2 dopamine receptor are methylated by PRMT5, and that this modification enhances D2-like dopamine receptor signaling in both cultured human cells (D2) and in C. elegans (DOP-3). These GPCRs represent the founding members of a new class of proteins that are functionally regulated by arginine methylation. Moreover, their work delineates 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

• 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 elegans. Genetics. 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. elegans. PLoS 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. elegans. Genetics. 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. doi:10.1371/journal.pgen.1006153. 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. doi:10.1371/journal.pgen.1003619. 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.  doi:10.1371/journal.pone.0025047. 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. doi:10.1371/journal.pone.0009487 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.