A diverse array of organisms including prokaryotic and eukaryotic microbes, plants, and animals display daily rhythms in physiology, metabolism and/or behavior. These rhythms are not passively driven by environmental cycles of light and temperature, but are actively controlled by endogenous circadian clocks that are set by environmental cycles, keep time in the absence of environmental cues, and activate overt physiological, metabolic and behavioral rhythms at the appropriate time of day. This remarkable conservation of circadian clock function through evolution suggests that maintaining synchrony with the environment is of fundamental importance. Our understanding of the circadian clock is particularly important for human health and well-being. The clearest examples of circadian clock dysfunction are those that result in abnormal sleep-wake cycles, but clock disturbances are also associated with other ailments including epilepsy, cerebrovascular disease, depression, and seasonal affective disorder. The realization that disorders of the sleep-wake cycle such as Familial Advanced Sleep Phase Syndrome can result from alterations in clock gene function underscores the clinical importance of understanding the molecular organization of the circadian system.
Work in my laboratory focuses on defining the molecular mechanisms that drive circadian clock function in the fruit fly, Drosophila melanogaster. We previously found that the core timekeeping mechanism is based on core and interlocked transcriptional feedback loops. Our studies currently focus on (1) defining post-translational regulatory mechanisms that operate in the core loop to set the 24 hour period, (2) determining whether interlocked loops are important for circadian timekeeping and/or output, (3) understanding how circadian oscillator cells are determined during development, and (4) defining mechanisms that control rhythms in olfactory and gustatory physiology and behavior.
- Howard Hughes Medical Institute - (Chevy Chase, Maryland, United States), Postdoctoral Training 1991
- Ph.D. in Genetics, Indiana University Bloomington - (Bloomington, Indiana, United States) 1987
- B.S. in Biology, Southern Methodist University - (Dallas, Texas, United States) 1982
- Fuentes, N. R., Mlih, M., Barhoumi, R., Fan, Y., Hardin, P., Steele, T. J., ... Chapkin, R. S. (2018). Long chain n-3 fatty acids attenuate oncogenic KRas-driven proliferation by altering plasma membrane nanoscale proteolipid composition. CANCER RESEARCH. 78(14), canres.0324.2018-3912.
- Chatterjee, A., Lamaze, A., De, J., Mena, W., ChÃ©lot, E., Martin, B., ... Rouyer, F. (2018). Reconfiguration of a Multi-oscillator Network by Light in the Drosophila Circadian Clock. Current biology : CB. 28(13), 2007-2017.e4.
- Siwicki, K. K., Hardin, P. E., & Price, J. L. (2018). Reflections on contributing to â€œbig discoveriesâ€ about the fly clock: Our fortunate paths as post-docs with 2017 Nobel laureates Jeff Hall, Michael Rosbash, and Mike Young. Neurobiology of Sleep and Circadian Rhythms.
- Liu, T., Mahesh, G., Yu, W., & Hardin, P. E. (2017). CLOCK stabilizes CYCLE to initiate clock function in Drosophila. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES. 114(41), 10972-10977.
- Agrawal, P., Houl, J. H., Gunawardhana, K. L., Liu, T., Zhou, J., Zoran, M. J., & Hardin, P. E. (2017). Drosophila CRY Entrains Clocks in Body Tissues to Light and Maintains Passive Membrane Properties in a Non-clock Body Tissue Independent of Light. Current biology : CB. 27(16), 2431-+.
- Gunawardhana, K. L., & Hardin, P. E. (2017). VRILLE Controls PDF Neuropeptide Accumulation and Arborization Rhythms in Small Ventrolateral Neurons to Drive Rhythmic Behavior in Drosophila. Current biology : CB. 27(22), 3442-3453.e4.
- Zhang, Y., Markert, M. J., Groves, S. C., Hardin, P. E., & Merlin, C. (2017). Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES. 114(36), e7516-e7525.
- Agrawal, P., & Hardin, P. E. (2016). An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock. G3 (Bethesda, Md.). 6(12), 4227-4238.
- Zhou, J., Yu, W., & Hardin, P. E. (2016). CLOCKWORK ORANGE Enhances PERIOD Mediated Rhythms in Transcriptional Repression by Antagonizing E-box Binding by CLOCK-CYCLE. PLoS Genet. 12(11), e1006430-e1006430.
- Agrawal, P., & Hardin, P. E. (2016). The Drosophila Receptor Protein Tyrosine Phosphatase LAR Is Required for Development of Circadian Pacemaker Neuron Processes That Support Rhythmic Activity in Constant Darkness But Not during Light/Dark Cycles. The Journal of Neuroscience. 36(13), 3860-3870.
- Zhou, J., Yu, W., & Hardin, P. E. (2015). ChIPping Away at the Drosophila Clock. GUIDE TO TECHNIQUES IN MOUSE DEVELOPMENT, PT A: MICE, EMBRYOS, AND CELLS, 2ND EDITION. 551, 323-347.
- Liu, T., Mahesh, G., Houl, J. H., & Hardin, P. E. (2015). Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila. The Journal of Neuroscience. 35(22), 8662-8671.
- Menet, J. S., & Hardin, P. E. (2014). Circadian Clocks: The Tissue Is the Issue. Current biology : CB. 24(1), R25-R27.
- Glossop, N., Gummadova, J. O., Ghangrekar, I., Hardin, P. E., & Coutts, G. A. (2014). Effects of TWIN-OF-EYELESS on Clock Gene Expression and Central-Pacemaker Neuron Development in Drosophila. JOURNAL OF BIOLOGICAL RHYTHMS. 29(3), 151-166.
- Lee, E., Jeong, E. H., Jeong, H., Yildirim, E., Vanselow, J. T., Ng, F., ... Kim, E. Y. (2014). Phosphorylation of a Central Clock Transcription Factor Is Required for Thermal but Not Photic Entrainment. PLoS Genet. 10(8), e1004545-e1004545.
- Mahesh, G., Jeong, E., Ng, F. S., Liu, Y., Gunawardhana, K., Houl, J. H., ... Hardin, P. E. (2014). Phosphorylation of the Transcription Activator CLOCK Regulates Progression through a similar to 24-h Feedback Loop to Influence the Circadian Period in Drosophila. JOURNAL OF BIOLOGICAL CHEMISTRY. 289(28), 19681-19693.
- Hardin, P. E., & Panda, S. (2013). Circadian timekeeping and output mechanisms in animals. Curr Opin Neurobiol. 23(5), 724-731.
- Kaneko, H., Head, L. M., Ling, J., Tang, X., Liu, Y., Hardin, P. E., Emery, P., & Hamada, F. N. (2012). Circadian Rhythm of Temperature Preference and Its Neural Control in Drosophila. Current biology : CB. 22(19), 1851-1857.
- Hardin, P. E. (2011). Molecular Genetic Analysis of Circadian Timekeeping in Drosophila. GENETICS OF CIRCADIAN RHYTHMS. 74, 141-173.
- Yu, W., Houl, J. H., & Hardin, P. E. (2011). NEMO Kinase Contributes to Core Period Determination by Slowing the Pace of the Drosophila Circadian Oscillator. Current biology : CB. 21(9), 756-761.
- Zhang, L., Chung, B. Y., Lear, B. C., Kilman, V. L., Liu, Y., Mahesh, G., ... Allada, R. (2010). DN1(p) Circadian Neurons Coordinate Acute Light and PDF Inputs to Produce Robust Daily Behavior in Drosophila. Current biology : CB. 20(7), 591-599.
- Zhang, Y., Liu, Y., Bilodeau-Wentworth, D., Hardin, P. E., & Emery, P. (2010). Light and Temperature Control the Contribution of Specific DN1 Neurons to Drosophila Circadian Behavior. Current biology : CB. 20(7), 600-605.
- Chatterjee, A., Tanoue, S., Houl, J. H., & Hardin, P. E. (2010). Regulation of Gustatory Physiology and Appetitive Behavior by the Drosophila Circadian Clock. Current biology : CB. 20(4), 300-309.
- Benito, J., Hoxha, V., Lama, C., Lazareva, A. A., Ferveur, J., Hardin, P. E., & Dauwalder, B. (2010). The circadian output gene takeout is regulated by Pdp1ε. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES. 107(6), 2544-2549.
- Chatterjee, A., & Hardin, P. E. (2010). Time to taste Circadian clock function in the Drosophila gustatory system. FLY. 4(4), 283-287.
- Wangjie, Y. u., & Hardin, P. E. (2013). An RNAi screen of protein kinase genes identifies novel components of the circadian oscillator in Drosophila. JOURNAL OF PHYSIOLOGICAL SCIENCES. 63, S111-S111.
- Benito, J., Zheng, H., Ng, F. S., & Hardin, P. E. (2007). Transcriptional feedback loop regulation, function, and ontogeny in Drosophila. Symposia on Quantitative Biology. 72(1), 437-444.
- Ng, F. S., Houl, J. H., Francis, C., Callaerts, P., & Hardin, P. E. (2006). CLOCK expression and regulation during development in Drosophila. Journal of Neurogenetics. 20(3-4), 189-189.
- Zwiebel, L. J., Hardin, P. E., Hall, J. C., & Rosbash, M. (1991). Circadian oscillations in protein and mRNA levels of the period gene of Drosophila melanogaster.. Biochem Soc Trans. 19(2), 533-537.
- Circadian clock activation and tissue specificity in Drosophila awarded by National Institutes of Health 2015 - 2018
- NIh-Developing Cell Lines From Clock Neurons In Drosophila awarded by National Institutes of Health 2012 - 2015
- Moores Professorship conferred by University of Houston - (Houston, Texas, United States) 2004
- Gunawardhana, Kushan Lakshitha (2018-05). Characterization of Vrille Function in the Drosophila Circadian Clock. (Doctoral Dissertation)
- Liu, Tianxin (2017-08). Circadian Clock Development and Initiation in Drosophila melanogaster. (Doctoral Dissertation)
- Caster, Courtney Marie (2017-08). Investigating the Evolution of the Molecular Clock Mechanism Using the Housefly, Musca domestica. (Master's Thesis)
- Zhou, Jian (2017-08). Characterizing the Function of Clockwork Orange in the Circadian Feedback Loops in Drosophila melanogaster. (Doctoral Dissertation)
- Agrawal, Parul (2016-08). Characterizing Novel Circadian Clock Functions for Drosophila Phosphatases and Non-clock Functions for Circadian Photoreceptors. (Doctoral Dissertation)
- Chatterjee, Abhishek (2011-05). Connecting the Circadian Clock with Chemosensation. (Doctoral Dissertation)
- Krishnan, Parthasarathy (2008-05). Cellular and molecular mechanisms that regulate olfactory rhythms in drosophila melanogaster. (Doctoral Dissertation)