Joined the Department in 2005
- B.S., 1982, Southern Methodist University, Biology.
- Ph.D., 1987, Indiana University, Genetics.
- Postdoctoral research, Brandeis University.
- Department of Biology faculty, 1991-1995.
- Prior faculty appointments at Texas A&M (1991-1995) and University of Houston (1995-2005)
Molecular Genetics of Biological Clocks
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.
- Zhang, Y, Markert, MJ, Groves, SC, Hardin, PE, Merlin, C. Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity. Proc. Natl. Acad. Sci. U.S.A. 2017;114 (36):E7516-E7525. doi: 10.1073/pnas.1702014114. PubMed PMID:28831003 .
- Agrawal, P, Houl, JH, Gunawardhana, KL, Liu, T, Zhou, J, Zoran, MJ et al.. Drosophila CRY Entrains Clocks in Body Tissues to Light and Maintains Passive Membrane Properties in a Non-clock Body Tissue Independent of Light. Curr. Biol. 2017;27 (16):2431-2441.e3. doi: 10.1016/j.cub.2017.06.064. PubMed PMID:28781048 .
- Zhou, J, Yu, W, Hardin, PE. CLOCKWORK ORANGE Enhances PERIOD Mediated Rhythms in Transcriptional Repression by Antagonizing E-box Binding by CLOCK-CYCLE. PLoS Genet. 2016;12 (11):e1006430. doi: 10.1371/journal.pgen.1006430. PubMed PMID:27814361 PubMed Central PMC5096704.
- Agrawal, P, Hardin, PE. An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock. G3 (Bethesda). 2016;6 (12):4227-4238. doi: 10.1534/g3.116.035345. PubMed PMID:27784754 PubMed Central PMC5144990.
- Agrawal, P, Hardin, PE. 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. J. Neurosci. 2016;36 (13):3860-70. doi: 10.1523/JNEUROSCI.4523-15.2016. PubMed PMID:27030770 PubMed Central PMC4812141.
- Liu, T, Mahesh, G, Houl, JH, Hardin, PE. Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila. J. Neurosci. 2015;35 (22):8662-71. doi: 10.1523/JNEUROSCI.0250-15.2015. PubMed PMID:26041931 PubMed Central PMC4452561.
- Zhou, J, Yu, W, Hardin, PE. ChIPping away at the Drosophila clock. Meth. Enzymol. 2015;551 :323-47. doi: 10.1016/bs.mie.2014.10.019. PubMed PMID:25662463 .
- Lee, E, Jeong, EH, Jeong, HJ, Yildirim, E, Vanselow, JT, Ng, F et al.. Phosphorylation of a central clock transcription factor is required for thermal but not photic entrainment. PLoS Genet. 2014;10 (8):e1004545. doi: 10.1371/journal.pgen.1004545. PubMed PMID:25121504 PubMed Central PMC4133166.
- Glossop, NR, Gummadova, JO, Ghangrekar, I, Hardin, PE, Coutts, GA. Effects of TWIN-OF-EYELESS on Clock Gene Expression and Central-Pacemaker Neuron Development in Drosophila. J. Biol. Rhythms. 2014;29 (3):151-166. doi: 10.1177/0748730414534819. PubMed PMID:24916389 PubMed Central PMC4262727.
- Mahesh, G, Jeong, E, Ng, FS, Liu, Y, Gunawardhana, K, Houl, JH et al.. Phosphorylation of the transcription activator CLOCK regulates progression through a ∼ 24-h feedback loop to influence the circadian period in Drosophila. J. Biol. Chem. 2014;289 (28):19681-93. doi: 10.1074/jbc.M114.568493. PubMed PMID:24872414 PubMed Central PMC4094078.