Research Projects

Mammalian Olfactory Receptors
The process of olfaction is an immense ligand recognition task and mammalian olfaction is particularly impressive.  Humans, who are thought to have relatively poor olfactory abilities when compared to other mammals, can detect hundreds of thousands (perhaps millions) of compounds and when trained, can reliably identify several thousand compounds.  To accomplish this remarkable feat of ligand recognition, the olfactory system employs a vast family of odorant receptors (~350 ORs in humans, ~1000 ORs in mouse).  ORs are thought to be employed in a combinatorial fashion, with each odorant recognized by a group of ORs and each OR recognizing a variety of odorant molecules.  Thus, understanding the odorant specificities of individual ORs is critical to understanding odorant coding. In addition, the study of ORs may provide benefits beyond the chemosensory field.  Mammalian ORs are G-protein coupled receptors and the study of the structural basis for ligand specificity among ORs offers the opportunity to examine the strategies employed by GPCRs to recognize a wide variety of ligand structural features.  This could provide insight into the fundamental principles of ligand recognition by this therapeutically important receptor class and these insights could be of value in future rational drug design efforts.
Recent Publications
Kepchia, D., Sherman, B., Haddad, R., Luetje, C.W. (2017) Mammalian Odorant Receptor Tuning Breadth Persists Across Distinct Odorant Panels.  PLoS One 12: e0185329. 
Li, J., Haddad, R., Santos, V., Bavan, S., Luetje, C.W. (2015) Receptive range analysis of a mouse odorant receptor subfamily.  Journal of Neurochemistry 134: 47-55.  
Luetje, C.W. (2013) Chemical courtship in mice. Nature Chemical Biology 9: 140-141.
Luetje, C.W., Nichols A.S., Castro A., Sherman B.L. (2013) Functional assay of mammalian and insect olfactory receptors using Xenopus oocytes.  Methods in Molecular Biology 1003:187-202.
Li, J., Haddad, R., Chen, S., Santos, V., Luetje, C.W. (2012) A broadly tuned mouse odorant receptor that detects nitrotoluenes.  Journal of Neurochemistry 121(6):881-890.  
Goldsmith, B.R., Mitala, Jr., J.J., Josue, J., Castro, A., Lerner, M.B., Bayburt, T.H., Khamis, S.M., Jones, R.A., Brand, J.G., Sligar, S.G., Luetje, C.W., Gelperin, A., Rhodes, P.A., Discher, B.M., Johnson, A.T.C. (2011) Biomimetic chemical sensors using nanoelectronic read out of olfactory receptor proteins.  ACS Nano 5:5408-5416. 
Repicky, S.E., Luetje, C.W. (2009) Molecular receptive range variation among mouse odorant receptors for aliphatic carboxylic acids.  Journal of Neurochemistry 109:193-202.
Menashe, I., Abaffy, T., Hasin, Y., Goshen, S., Yahalom, V., Luetje, C.W., Lancet, D. (2007) Genetic Elucidation of Human Hyperosmia to Isovaleric Acid.  PLoS Biology 5:e284.
Abaffy, T., Malhotra, A., Luetje, C.W. (2007) The molecular basis for ligand specificity in a mouse olfactory receptor: A network of functionally important residues.  Journal of Biological Chemistry 282:1216-1224.
Abaffy, T., Matsunami, H., Luetje, C.W. (2006) Functional analysis of a mammalian odorant receptor subfamily.  Journal of Neurochemistry 97:1506-1518.