Timothy S McClintock, Ph.D.

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mcclint@uky.edu
(859) 323-1083
800 Rose Street, Medical Science Building, Rm: MS-585, Lexington, KY 40536-0298
McClintock web CV 2017.docx

Position(s):

Louis Boyarsky Professor

Affiliation(s):

Physiology

Interests / Specialties:

Molecular Biology and Functional Genomics of Olfaction

Neural Regeneration

Bio / Education:

B.S. Michigan State University, 1982
M.S. Florida State University, 1984
Ph.D. University of Florida, 1989
Postdoctoral: Yale University, HHMI, 1993

Research Description:

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.

Odorant receptors comprise the largest gene family in mammals, with up to 1500 genes in some species, yet each olfactory sensory neuron expresses only one allele of one of these genes. We are investigating the mechanisms that underlie this amazing specificity of gene expression, as well as the patterns of odorant receptors activated by odors in vivo. Unlike vision and hearing, the details of how the receptors allow discrimination of stimulus quality (e.g., color, pitch) are unknown. The physiology of the odorant receptors, and the remarkable singularity of their expression, must be fundamental to odor discrimination.

The process of neural replacement in the olfactory epithelial is a natural example of the therapeutic process that many envision as the future of treatment for neurodegenerative disorders and neurotrauma. We investigate the molecular and cellular mechanisms that control olfactory neurogenesis, such as the ability of transcription factors to control gene expression, both directly and through epigenetic mechanisms.

Both of these projects are informed by the application of molecular systems biology to the olfactory system. For example, we have developed approaches that are allowing us to map the expression of every gene in each of the cell types in the olfactory epithelium.

Technologically, we use physiological genomics techniques, such as microarrays, to observe system-wide effects and then use techniques focused on specific processes or genes, such as targeted gene deletion (gene knockout), electrophysiology, biochemistry, and anatomy to plumb the depths of regulatory networks of proteins controlling function. The mouse is our primary experimental model.

Website: http://www.mc.uky.edu/physiology/mcclintock/mcclintock.asp

Data Page: http://www.mc.uky.edu/physiology/mcclintock/downloads.asp

Selected Publications:

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.

Other Publications

PubMed Publications:

Wang, Q.;Titlow, W.B.;McClintock, D.A.;Stromberg, A.J.;McClintock, T.S. "Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium." Chemical senses 42, 8 (2017): 611-624. [PubMed Link] | [ Full text ]
Zhang, G.;Titlow, W.B.;Biecker, S.M.;Stromberg, A.J.;McClintock, T.S. "Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons." eNeuro 3, 5 (2016): [PubMed Link] |
Kirby, T.J.;Patel, R.M.;McClintock, T.S.;Dupont-Versteegden, E.E.;Peterson, C.A.;McCarthy, J.J. "Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy." Molecular biology of the cell 27, 5 (2016): 788-98. [PubMed Link] | [ Full text ]
McClintock, T.S. "Odorant Receptor Gene Choice." ChemoSense 16, 2 (2015): 3-13. [PubMed Link] |
McClintock, T.S.;Adipietro, K.;Titlow, W.B.;Breheny, P.;Walz, A.;Mombaerts, P.;Matsunami, H. "In vivo identification of eugenol-responsive and muscone-responsive mouse odorant receptors." The Journal of neuroscience : the official journal of the Society for Neuroscience 34, 47 (2014): 15669-78. [PubMed Link] | [ Full text ]
Fischl, A.M.;Heron, P.M.;Stromberg, A.J.;McClintock, T.S. "Activity-dependent genes in mouse olfactory sensory neurons." Chemical senses 39, 5 (2014): 439-49. [PubMed Link] | [ Full text ]
Heron, P.M.;Stromberg, A.J.;Breheny, P.;McClintock, T.S. "Molecular events in the cell types of the olfactory epithelium during adult neurogenesis." Molecular brain 6, (2013): 49. [PubMed Link] | [ Full text ]
Nickell, M.D.;Breheny, P.;Stromberg, A.J.;McClintock, T.S. "Genomics of mature and immature olfactory sensory neurons." The Journal of comparative neurology 520, 12 (2012): 2608-29. [PubMed Link] | [ Full text ]
Ferrari, M.;Folli, C.;Pincolini, E.;McClintock, T.S.;Rössle, M.;Berni, R.;Cianci, M. "Structural characterization of recombinant crustacyanin subunits from the lobster Homarus americanus." Acta crystallographica. Section F, Structural biology and crystallization communications 68, Pt 8 (2012): 846-53. [PubMed Link] | [ Full text ]
McIntyre, J.C.;Titlow, W.B.;McClintock, T.S. "Axon growth and guidance genes identify nascent, immature, and mature olfactory sensory neurons." Journal of neuroscience research 88, 15 (2010): 3243-56. [PubMed Link] | [ Full text ]
Sammeta, N.;McClintock, T.S. "Chemical stress induces the unfolded protein response in olfactory sensory neurons." The Journal of comparative neurology 518, 10 (2010): 1825-36. [PubMed Link] | [ Full text ]
McClintock, T.S. "Achieving singularity in mammalian odorant receptor gene choice." Chemical senses 35, 6 (2010): 447-57. [PubMed Link] | [ Full text ]
Sammeta, N.;Hardin, D.L.;McClintock, T.S. "Uncx regulates proliferation of neural progenitor cells and neuronal survival in the olfactory epithelium." Molecular and cellular neurosciences 45, 4 (2010): 398-407. [PubMed Link] | [ Full text ]
Dickinson, P.S.;Stemmler, E.A.;Barton, E.E.;Cashman, C.R.;Gardner, N.P.;Rus, S.;Brennan, H.R.;McClintock, T.S.;Christie, A.E. "Molecular, mass spectral, and physiological analyses of orcokinins and orcokinin precursor-related peptides in the lobster Homarus americanus and the crayfish Procambarus clarkii." Peptides 30, 2 (2009): 297-317. [PubMed Link] | [ Full text ]
McClintock, T.S.;Wilson, D.A.;Munger, S.D.;Geran, L.;Herness, S. "The 15th International Symposium on Olfaction and Taste." Chemical senses 33, 8 (2008): 735-8. [PubMed Link] | [ Full text ]
McIntyre, J.C.;Bose, S.C.;Stromberg, A.J.;McClintock, T.S. "Emx2 stimulates odorant receptor gene expression." Chemical senses 33, 9 (2008): 825-37. [PubMed Link] | [ Full text ]
McClintock, T.S.;Glasser, C.E.;Bose, S.C.;Bergman, D.A. "Tissue expression patterns identify mouse cilia genes." Physiological genomics 32, 2 (2008): 198-206. [PubMed Link] | [ Full text ]
Sammeta, N.;Yu, T.T.;Bose, S.C.;McClintock, T.S. "Mouse olfactory sensory neurons express 10,000 genes." The Journal of comparative neurology 502, 6 (2007): 1138-56. [PubMed Link] | [ Full text ]
McClintock, T.S.;Ache, B.W.;Derby, C.D. "Lobster olfactory genomics." Integrative and comparative biology 46, 6 (2006): 940-7. [PubMed Link] | [ Full text ]
Stepanyan, R.;Day, K.;Urban, J.;Hardin, D.L.;Shetty, R.S.;Derby, C.D.;Ache, B.W.;McClintock, T.S. "Gene expression and specificity in the mature zone of the lobster olfactory organ." Physiological genomics 25, 2 (2006): 224-33. [PubMed Link] | [ Full text ]
McClintock, T.S.;Derby, C.D. "Shelling out for genomics." Genome biology 7, 4 (2006): 312. [PubMed Link] | [ Full text ]
Shetty, R.S.;Bose, S.C.;Nickell, M.D.;McIntyre, J.C.;Hardin, D.H.;Harris, A.M.;McClintock, T.S. "Transcriptional changes during neuronal death and replacement in the olfactory epithelium." Molecular and cellular neurosciences 30, 1 (2005): 90-107. [PubMed Link] | [ Full text ]
Stepanyan, R.;Haley, S.B.;McClintock, T.S. "Olfactory specific chymotrypsin-like serine protease from the aesthetasc tegumental gland of the lobster, Homarus americanus." Cell and tissue research 322, 2 (2005): 321-30. [PubMed Link] | [ Full text ]
Yu, T.T.;McIntyre, J.C.;Bose, S.C.;Hardin, D.;Owen, M.C.;McClintock, T.S. "Differentially expressed transcripts from phenotypically identified olfactory sensory neurons." The Journal of comparative neurology 483, 3 (2005): 251-62. [PubMed Link] | [ Full text ]
Shetty, R.S.;Bose, S.C.;Nickell, M.D.;McIntyre, J.C.;Hardin, D.H.;Harris, A.M.;McClintock, T.S. "Transcriptional changes during neuronal death and replacement in the olfactory epithelium." Molecular and cellular neurosciences 30, 4 (2005): 583-600. [PubMed Link] |
Stepanyan, R.;Hollins, B.;Brock, S.E.;McClintock, T.S. "Primary culture of lobster (Homarus americanus) olfactory sensory neurons." Chemical senses 29, 3 (2004): 179-87. [PubMed Link] |
Stoss, T.D.;Nickell, M.D.;Hardin, D.;Derby, C.D.;McClintock, T.S. "Inducible transcript expressed by reactive epithelial cells at sites of olfactory sensory neuron proliferation." Journal of neurobiology 58, 3 (2004): 355-68. [PubMed Link] |
Hollins, B.;Hardin, D.;Gimelbrant, A.A.;McClintock, T.S. "Olfactory-enriched transcripts are cell-specific markers in the lobster olfactory organ." The Journal of comparative neurology 455, 1 (2003): 125-38. [PubMed Link] | [ Full text ]
McClintock, T.S.;Sammeta, N. "Trafficking prerogatives of olfactory receptors." Neuroreport 14, 12 (2003): 1547-52. [PubMed Link] | [ Full text ]
McClintock, T.S. "High-throughput expression profiling techniques." Chemical senses 27, 3 (2002): 289-91. [PubMed Link] |
Gimelbrant, A.A.;Haley, S.L.;McClintock, T.S. "Olfactory receptor trafficking involves conserved regulatory steps." The Journal of biological chemistry 276, 10 (2001): 7285-90. [PubMed Link] | [ Full text ]
McClintock, T.S.;Xu, F.;Bose, S.C. "Distribution of G-protein alpha subunits and neurotransmitter activation of g(alphai) and g(alphaq) in the brain of the lobster Homarus americanus." The Journal of comparative neurology 422, 3 (2000): 402-14. [PubMed Link] | [ Full text ]
Hollins, B.;McClintock, T.S. "Lobster GABA receptor subunit expressed in neural tissues." Journal of neuroscience research 59, 4 (2000): 534-41. [PubMed Link] | [ Full text ]
Xu, F.;McClintock, T.S. "A lobster phospholipase C-beta that associates with G-proteins in response to odorants." The Journal of neuroscience : the official journal of the Society for Neuroscience 19, 12 (1999): 4881-8. [PubMed Link] | [ Full text ]
Gimelbrant, A.A.;Stoss, T.D.;Landers, T.M.;McClintock, T.S. "Truncation releases olfactory receptors from the endoplasmic reticulum of heterologous cells." Journal of neurochemistry 72, 6 (1999): 2301-11. [PubMed Link] | [ Full text ]
Xu, F.;Bose, S.C.;McClintock, T.S. "Lobster G-protein coupled receptor kinase that associates with membranes and G(beta) in response to odorants and neurotransmitters." The Journal of comparative neurology 415, 4 (1999): 449-59. [PubMed Link] | [ Full text ]
Xu, F.;Hollins, B.;Landers, T.M.;McClintock, T.S. "Molecular cloning of a lobster Gbeta subunit and Gbeta expression in olfactory receptor neuron dendrites and brain neuropil." Journal of neurobiology 36, 4 (1998): 525-36. [PubMed Link] |
Mankad, R.V.;Gimelbrant, A.A.;McClintock, T.S. "Consensus translational initiation sites of marine invertebrate phyla." The Biological bulletin 195, 3 (1998): 251-4. [PubMed Link] | [ Full text ]
McClintock, T.S.;Landers, T.M.;Gimelbrant, A.A.;Fuller, L.Z.;Jackson, B.A.;Jayawickreme, C.K.;Lerner, M.R. "Functional expression of olfactory-adrenergic receptor chimeras and intracellular retention of heterologously expressed olfactory receptors." Brain research. Molecular brain research 48, 2 (1997): 270-8. [PubMed Link] | [ Full text ]
Xu, F.;Hollins, B.;Gress, A.M.;Landers, T.M.;McClintock, T.S. "Molecular cloning and characterization of a lobster G alphaS protein expressed in neurons of olfactory organ and brain." Journal of neurochemistry 69, 5 (1997): 1793-800. [PubMed Link] | [ Full text ]
McClintock, T.S.;Xu, F.;Quintero, J.;Gress, A.M.;Landers, T.M. "Molecular cloning of a lobster G alpha(q) protein expressed in neurons of olfactory organ and brain." Journal of neurochemistry 68, 6 (1997): 2248-54. [PubMed Link] | [ Full text ]
McClintock, T.S.;Lerner, M.R. "Functional analysis by imaging of melanophore pigment dispersion of chimeric receptors constructed by recombinant polymerase chain reaction." Brain research. Brain research protocols 2, 1 (1997): 59-68. [PubMed Link] | [ Full text ]
Gimelbrant, A.A.;McClintock, T.S. "A nuclear matrix attachment region is highly homologous to a conserved domain of olfactory receptors." Journal of molecular neuroscience : MN 9, 1 (1997): 61-3. [PubMed Link] |
Lerner, M.R.;Golovyan, L.;Graminski, G.F.;Harris, K.;Huang, L.;Jayawickreme, C.K.;Karne, S.;McClintock, T.S.;Potenza, M.N.;Roby-Shemkovitz, A.;Quillan, M. "Tools for Investigating Functional Interactions Between Lipid-Derived Autacoids and their Receptors." American journal of therapeutics 3, 4 (1996): 280-286. [PubMed Link] |
McClintock, T.S.;Rising, J.P.;Lerner, M.R. "Melanophore pigment dispersion responses to agonists show two patterns of sensitivity to inhibitors of cAMP-dependent protein kinase and protein kinase C." Journal of cellular physiology 167, 1 (1996): 1-7. [PubMed Link] | [ Full text ]
McClintock, T.S.;Graminski, G.F.;Potenza, M.N.;Jayawickreme, C.K.;Roby-Shemkovitz, A.;Lerner, M.R. "Functional expression of recombinant G-protein-coupled receptors monitored by video imaging of pigment movement in melanophores." Analytical biochemistry 209, 2 (1993): 298-305. [PubMed Link] | [ Full text ]
Pongrácz, F.;McClintock, T.S.;Ache, B.W.;Shepherd, G.M. "Signal transmission in lobster olfactory receptor cells: functional significance of electrotonic structure analysed by a compartmental model." Neuroscience 55, 2 (1993): 325-38. [PubMed Link] | [ Full text ]
McClintock, T.S.;Byrnes, A.P.;Lerner, M.R. "Molecular cloning of a G-protein alpha i subunit from the lobster olfactory organ." Brain research. Molecular brain research 14, 3 (1992): 273-6. [PubMed Link] | [ Full text ]
Michel, W.C.;McClintock, T.S.;Ache, B.W. "Inhibition of lobster olfactory receptor cells by an odor-activated potassium conductance." Journal of neurophysiology 65, 3 (1991): 446-53. [PubMed Link] | [ Full text ]
McClintock, T.S.;Ache, B.W. "Nonselective cation channel activated by patch excision from lobster olfactory receptor neurons." The Journal of membrane biology 113, 2 (1990): 115-22. [PubMed Link] |
Bayer, T.A.;McClintock, T.S.;Grünert, U.;Ache, B.W. "Histamine-induced modulation of olfactory receptor neurones in two species of lobster, Panulirus argus and Homarus americanus." The Journal of experimental biology 145, (1989): 133-46. [PubMed Link] | [ Full text ]
McClintock, T.S.;Ache, B.W. "Histamine directly gates a chloride channel in lobster olfactory receptor neurons." Proceedings of the National Academy of Sciences of the United States of America 86, 20 (1989): 8137-41. [PubMed Link] | [ Full text ]
McClintock, T.S.;Ache, B.W. "Ionic currents and ion channels of lobster olfactory receptor neurons." The Journal of general physiology 94, 6 (1989): 1085-99. [PubMed Link] | [ Full text ]