David J. Earnest, Ph.D.
8447 State Highway 47
2004 Medical Research & Education Building
Bryan, TX 77807-3260
Cellular and Molecular Neurobiology of Mammalian Circadian Rhythms
Normal regulation of 24-hour or circadian rhythms by the master biological clock in the suprachiasmatic nucleus (SCN) and by peripheral clocks throughout the body has an important impact on human health by providing for the temporal coordination of internal processes to occur at the “right time” relative to each other and to the external environment. Pathologies and environmental disturbances in the regulation of circadian rhythms have been linked to variety of human health disorders including obesity and diabetes, increased cancer risk, cardiovascular disease, sleep-wake cycle disturbances, and depression. Research in my laboratory employs multidisciplinary approaches to study the cellular and molecular neurobiology of cell-autonomous circadian clocks and the signal transduction pathway responsible for circadian photoentrainment. The aims of current projects are to study: 1) the role of microRNAs (miRNAs) and other signaling molecules in the local temporal coordination of cell- and tissue-specific circadian clocks; 2) mutual interactions between the circadian clock mechanism, inflammatory signaling and metabolism; and 3) the mechanisms linking circadian rhythm disruption with metabolic disorders such as obesity and diabetes, and with pathological changes in neuroprotective responses to stroke.
- Cell culture (explant, dissociated, cell lines, co-culture)
- Establishment of immortalized neural cell lines
- Gene transfer using retroviral vectors
- RT-PCR and in situ hybridization analysis of mRNA expression in brain and peripheral tissues
- Immunocytochemistry and immunoassay for neuropeptides
- Neural transplantation of fetal tissue and cells
- Real-time imaging of gene expression
- Analysis of rodent wheel-running behavior
- Facilities and equipment necessary for performing cell culture, immunocytochemical, immunoassay and molecular methodologies;
- Computer-based data Acquisition System for Monitoring Locomotor Behavior, and luciferase-reported bioluminescence.
I participate in graduate training as a member of the faculty in the Interdisciplinary Program in Neuroscience.
I am an executive member of the TAMU Center for Biological Clocks Research.
- Shende, V.R., Kim, S.-M., Neuendorff, N. and Earnest, D.J. (2014) MicroRNAs function as cis- and trans-acting modulators of peripheral circadian clocks. FEBS Letters 588: 3015-3022.
- Xu, H.,, Li, H., Woo, S.-L., Kim, S.-M., Neuendorff, N., Guo, X., Guo, T., Qi, T., Ji, J.-Y., Alaniz, R.C., Earnest, D.J.*, and Wu, C.* (2014) Myeloid cell-specific Circadian Clock Disruption Exacerbates Diet-induced Inflammation and Insulin Resistance. J. Biol. Chem. 289: 16374–16388. * Corresponding authors.
- Shende, V, Neuendorff, N. and Earnest, DJ. (2013) “Role of mir-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN”. PLoS ONE 8(6): e65300.
- Shende, V, Goldrick, M, Ramani, S, and Earnest, D. (2011) “Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice”. PLos One 6(7): e22586.
- Burkeen, J.F., Womac, A.D., Earnest, D.J. and Zoran, M.J. (2011) “Mitochondrial calcium signaling mediates rhythmic extracellular ATP accumulation in suprachiasmatic nucleus astrocytes”. J. Neurosci. 31: 8432-40.
- Farnell, YF, Shende, V, Neuendorff, N, Allen, GC and Earnest, DJ. (2011) “Immortalized cell lines for real-time analysis of circadian pacemaker and peripheral oscillator properties”. Eur. J. Neurosci. 33: 1533-40.
- Qu, X, Metz, RP, Porter, WW, Neuendorff, N, Earnest, BJ, and Earnest, DJ. (2010) “The clock genes Period 1 And Period 2 mediate diurnal rhythms in dioxin-induced CYP1A1 expression in the mouse mammary gland and liver”. Tox. Letters 196: 28-32.
- Womac, AD, Burkeen, JF, Neuendorff, N, Earnest, DJ and Zoran, MJ. (2009) “Circadian rhythms in extracellular ATP accumulation in SCN cells and cultured astrocytes”. Eur. J. Neuroscience 30: 869–76.
- Farnell, YZ, Allen, GC, Nahm, S-S, Neuendorff, N, West, JR, Chen, W-J and Earnest, DJ. (2009) “Effects of neonatal alcohol exposure on vasoactive intestinal polypeptide neurons in the rat suprachiasmatic nucleus”. Alcohol 43: 387-96.
- Qu, X, Metz, RP, Porter, WW, Cassone, VM and Earnest, DJ. (2009) “Disruption of period gene expression alters the inductive effects of dioxin on the AhR signaling pathway in the mouse liver”. Tox. Appl. Pharm. 234: 370–77.
- Farnell, YZ, Allen, GC, Nahm, SS, Neuendorff, N, West, JR, Chen, WJ and Earnest, DJ. (2008) "Neonatal alcohol exposure differentially alters clock gene oscillations within the suprachiasmatic nucleus, cerebellum and liver of adult rats". Alcohol. Clin. Exp. Res. 32: 544-52.
- Qu, X, Metz, RP, Porter, WW, Cassone, VM and Earnest, DJ. (2007) "Disruption of clock gene expression alters responses of the AhR signaling pathway in the mouse mammary gland". Mol. Pharm. 72: 1349-58.
- Menger, GJ, Allen, GC, Neuendorff, N, Nahm, SS, Thomas, T, Cassone, VM and Earnest, DJ. (2007) "Circadian profiling of the transcriptome in NIH/3T3 fibroblasts: comparison with rhythmic gene expression in SCN2.2 cells and the rat SCN". Physiological Genomics 29: 280-9.