Timothy S McClintock, PhD
Connect
859-323-1083mcclint@uky.edu
Positions
- Professor of Physiology
- University Research Professor
College Unit(s)
Biography and Education
Education
B.S. Michigan State University, 1982
M.S. Florida State University, 1984
Ph.D. University of Florida, 1989
Postdoctoral: Yale University School of Medicine, HHMI, 1993
Research
The olfactory system does two unique things: It detects odors and it replaces injured neurons by activating resident tissue-level stem cells, even in adults. My lab investigates the molecular physiology of both of these processes, but current emphases are on the function and pharmacology of the odorant receptors.
Odorant receptors comprise the largest gene family in mammals, with up to nearly 2,000 genes in some species. Every odor activates a distinct subset of these receptors, and because each olfactory sensory neuron expresses only one odorant receptor gene the pattern of receptor responses exactly determines the pattern of information the brain must use to perceive and discriminate odors. We invented a way to identify these receptor response patterns in vivo in mice and are using it to investigate what patterns arise, how they overlap, whether odorants interact at the receptors to cause unpredictable patterns, and whether we can modify the patterns in logical ways. We then determine whether these findings translate into effects on human odor perception.
Other interests include investigating why olfactory sensory neurons are susceptible to genetic risk factors for Alzheimer's Disease, the mechanisms underlying the amazing specificity of odorant receptor gene expression, and the molecular biology of neural replacement in the olfactory epithelium. Our foundational studies of gene expression in the cell types of the olfactory epithelium guide these studies and provide opportunities to understand how phenotypic differences arise.
Technologically, our approaches range from genomics to biochemistry, anatomy, and behavior. Mice and humans are our experimental models.
Selected Publications
2023. Wang, Q, T Sengoku, WB Titlow, JL Strange, and TS McClintock. Dissociation of Mouse Olfactory Mucosae for Fluorescence-Activated Cell Sorting of Olfactory Sensory Neurons. Methods in Molecular Biology. doi: 10.1007/978-1-0716-3425-7_9 . PMID: 37688728.
2022. Kahn, N, Y Alimova, SJ Clark, H Vekaria, AE Walsh, HC Williams, GS Hawk, P Sullivan, LA Johnson, and TS McClintock. Human APOE-e3 and APOE-e4 alleles have differential effects on mouse olfactory epithelium. J Alzheimers Dis. doi: 10.3233/JAD-215152. PMID: 34958025
2020. McClintock, TS, N Kahn, Y Alimova, M. Aulisio, DY Han, and PB Breheny. Encoding the odor of cigarette smoke. J. Neurosci. 40(37):7043-7053. DOI: 10.1523/JNEUROSCI.1144-20.2020. PMID: 32801155
2020. McClintock, TS, Q Wang, T Sengoku, WB Titlow, and PB Breheny. Mixture and concentration effects of odorant receptor response patterns in vivo. Chem Senses doi: 10.1093/chemse/bjaa032. PMID: 32427281
2020. De March CA, WB Titlow, T Sengoku, PB Breheny, H Matsunami, and TS McClintock. Modulation of the combinatorial code of odorant receptor response patterns in odorant mixtures. Mol. Cell. Neurosci. 104:103469 doi:10.1016/j.mcn.2020.103469 PMID: 32061665
2020. McClintock, TS, N Khan, X Chao, and JR Martens. Maturation of the olfactory sensory neuron and its cilia. Chem Senses, 45, DOI: 10.1093/chemse/bjaa070.
2017. Wang, Q, WB Titlow, DA McClintock, AJ Stromberg and TS McClintock. Activity-dependent gene expression in the mammalian olfactory epithelium. Chem Senses 42:611-624. PMID: 28525560
2016. Zhang, G, WB Titlow, SM Biecker, AJ Stromberg, and TS McClintock. Lhx2 determines odorant receptor expression frequency in mature olfactory sensory neurons. eNeuro Oct 31;3(5) DOI: 10.1523/ENEURO.0230-16.2016. PMID 278225003
2016. Kirby, TJ, RM Patel, TS McClintock, EE Dupont-Versteegden, CA Peterson, and JJ McCarthy. In vivo Myonuclear transcription is responsive to mechanical load and DNA contact but uncoupled from cell size during hypertrophy. Mol. Biol. Cell 27:788-798. PMID 26764089
2015. McClintock, TS. Odorant receptor gene choice. ChemoSense, 16:3-13.
2014. McClintock TS, K Adipietro, WB Titlow, P Breheny, A Walsh, P Mombaerts, and H Matsunami. In vivo identification of eugenol-responsive and muscone-responsive mouse odorant receptors. J. Neurosci. 34:15669-15678. PMID 25411495
2014. Fischl AM, PM Heron, AJ Stromberg, and TS McClintock. Activity-dependent genes in mouse olfactory sensory neurons. Chem Senses, 39:439-449. PMID: 24692514
2013. Heron PM, AJ Stromberg, P Breheny, and TS McClintock. Molecular events in the cell types of the olfactory epithelium during adult neurogenesis. Mol Brain, 6:49. PMID: 24267470
2012. Nickell MD, P Breheny, AJ Stromberg, and TS McClintock. Genomics of mature and immature olfactory sensory neurons. J. Comp. Neurol., 520:2608-2629.
2010. Sammeta, N and TS McClintock. Chemical stress induces the unfolded protein response in olfactory sensory neurons. J. Comp. Neurol., 518:1825-1836.
2010. McClintock, TS, Achieving singularity in mammalian odorant receptor gene choice. Chem Senses, 35:447-457.
2010. Sammeta, N, DL Hardin and TS McClintock. Uncx regulates and proliferation of neural progenitor cells and neuronal survival in the olfactory epithelium. Mol. Cell. Neurosci. 45:398-407.
2010. McIntyre, JC, WB Titlow, and TS McClintock. Axon growth and guidance genes identify nascent, immature, and mature olfactory sensory neurons. J. Neurosci. Res. 88:3243-3256.
2008. McIntyre, JC, SC Bose, AJ Stromberg and TS McClintock. Emx2 stimulates odorant receptor gene expression. Chem. Senses, 33:825-837.
2008. McClintock, TS, CE Glasser, SC Bose, and DA Bergman. Tissue expression patterns identify mouse cilia genes. Physiol. Genomics, 32:198-206.
2007. Sammeta, N, T-T Yu,, SC Bose and TS McClintock. Mouse olfactory sensory neurons express 10,000 genes. J. Comp. Neurol. 502:1138-1156.
2006. Stepanyan, R, K Day, J Urban, DH Hardin, RS Shetty, CD Derby, BW Ache and TS McClintock. Gene expression and specificity in the mature zone of the lobster olfactory organ. Physiol Genomics, 25:224-233.