Cytoskeleton, Development, Imaging, Neurobiology, Proteomics, Signal Transduction
Disease Research Interests
Aging Related Diseases, Neurological and Behavioral Disorders, Trauma, Bleeding & Tissue Regeneration
The neurobiology of time; engineering neuronal development and repair
Our major research thrusts are to understand: 1) signals that engage the circadian clockwork in the brain, 2) sub-cellular micro-environments that shape neuronal dendrites in development and repair, and 3) emergent behaviors of integrated neuronal systems.
Regarding the neurobiology of time, consider these observations. Why do birds sing in the morning, while frogs call at night? Why are heart attacks likely to strike before dawn, while asthmatic attacks generally occur after sunset? Why do we most often feel lethargic and depressed during the short, dark days of winter, while on long, sunny summer days, we feel energetic and alert? The answer to each of these questions lies in understanding the central role of the brain's clock in organizing our body functions around the major variable in the external world, the daily cycle of darkness and light. This circadian clock, located in the suprachiasmatic nucleus (SCN) of the brain, whose cellular processes mark the passage of time in near 24-hr cycles, is a fundamental life component. Circadian clocks impose temporal order on cells, tissues and organs throughout the body, modulating body processes over the day-night cycle. Our broad research objective is to understand how biological timing systems control integrative brain functions. Our focus is on the role of the actin cytoskeleton in signaling and clock coupling via peptides.
This major research thrust has important applications: Malfunctioning of the brain's circadian clock results in disorders in brain and organ function, which manifest themselves as clinical disorders of sleep, movement and neural degeneration, such as in Alzheimer's and Parkinson's diseases. The breadth of our systems-based analysis is generating insights into mechanisms that synchronize people to day and night, which is of proven importance to good health and disease-resistance. Outcomes will enhance understanding of substrates that generate long-term neural changes, with broad relevance for public health and disease prevention. They will enable strategies for ameliorating sleep, autonomic, degenerative, movement and cognitive disorders.
Regarding neuroengineering development, we are building upon campus excellence in molecular and cellular biology, nano-scale analytical chemistry, and bioengineering. We study signals that shape the outgrowth of neuronal protrusions that wire the nervous system. Our goal is to discover novel insights, solutions, and applications for neural repair and restoration of function through targeting critical molecules and processes that construct micro-networks during the normal wiring of the nervous system.
Regarding emergent behaviors of neuronal clusters, we are controlling microenvironments to understand and direct the sensing, integration and actuation properties of neurons and their interactions with other functional types of cellular clusters.
B.A., Grinnell College (Biology)
M.S., University of Hawaii (Zoology)
Ph.D., University of Toronto (Zoology)
Postdoc., University of California-Santa Cruz
Awards and Honors
NSF BRAIN EAGER. Gillette (PI), Popescu, Rogers, Sweedler. 2014-17
NIH BRAIN Innovation Award. Sweedler (PI), Gillette, Bhargava. 2015-18
NSF Science & Technology Center CBET-0939511: EBICS: Emergent Behavior of Integrated Cellular Systems. Kamm (PI), with MIT, Georgia Tech, UC Merced, Morehouse, CUNY, Participant. 2010 – 20
Center for Advanced Study Professor
Women in Neuroscience Lifetime Achievement Award
Lee, M.K., M.H. Rich, A. Shkumatov, J.H. Jeong, M.D. Boppart, R. Bashir, M.U. Gillette, J. Lee, H. Kong. 2015. Glacier moraine formation-mimicking colloidal particle assembly in microchanneled, Bbioactive hydrogel for guided vascular network construction. Adv. Healthcare. Materials. 2015 Jan 4 (2):195-201. Epub 2014 Jun 4. doi: 10.1002/adhm.201400153. [Epub ahead of print] PMID: 24898521; PMCID: PMC Journal - In Process
Jain, A. and M.U. Gillette. 2015. Development of microfluidic devices for the manipulation of neuronal synapses. In: Microfluidic and Compartmentalized Platforms for Neurobiological Research: Neuromethods 103, Emilia Biffi, Ed., Wolfgang Walz, Editor-in-Chief, v. 103 Springer Science+Business Media New York, pp. 127-137. DOI 10.1007/978-1-4939-2510
Yang, N., S.J. Irving, E.V. Romanova, J.W. Mitchell, M.U. Gillette, J.V. Sweedler. 2015. Neuropeptidomics: the characterization of neuropeptides and hormones in the nervous and neuroendocrine systems. International Neuroendocrine Federation (INF) Masterclass Series: "Molecular Neuroendocrinology.” In press.
Froeter, P., Y. Huang Y, O.V. Cangellaris, W. Huang, E.W. Dent, M.U. Gillette, J.C. Williams, X. Li. 2014. Toward intelligent synthetic neural circuits: directing and accelerating neuron cell growth by self-rolled-up silicon nitride microtube array. ACS Nano. 2014 Nov 25; 8(11):11108-17. PMID: 25329686
Iyer, R., T.A. Wang, M.U. Gillette. 2014. Circadian gating of neuronal functionality: a basis for iterative metaplasticity. In "Sleep and Circadian Rhythms in Plasticity and Memory,” J. Gerstner, H.C. Heller, S. Aton, Eds. Front. Systems Neurosci. 2014 September 19 8: 164, 14 pp; PMCID: PMC4168688
Southey, B.R., J.E. Lee, L. Zamdborg, N. Atkins, Jr., J,W. Mitchell, M. Li, M.U. Gillette, N.L. Kelleher, J.V. Sweedler. 2014. Comparing label-free quantitative peptidomics approaches to characterize diurnal variation of peptides in the rat suprachiasmatic nucleus. Anal. Chem. 86(1): 443–452. PMCID: PMC3886391
Mir, M., T. Kim, A. Majumder, M. Xiang, R. Wang, S.C. Liu, M.U. Gillette, S. Stice, and G. Popescu. 2014. Label-free characterization of self-organizing human neuronal networks. Scientific Reports 4: 4434 (8 pg). PMCID: PMC3963031
Gillette, M.U. and T.A. Wang. 2014. Brain oscillators and redox regulation in mammals. In Forum Issue on “Circadian clocks and redox signaling,” A. Reddy, Ed. Antioxidants & Redox Signaling (ARS) 2014 Feb10; 20(17): 2955-2965.; PMCID: PMC4038987
Abbott, S.M., J.M. Arnold, Q. Chang, H. Miao, N. Ota, C. Cecala, P.E. Gold, J.V. Sweedler, M.U. Gillette. 2013. Signals from the brainstem arousal centers regulate behavioral timing via the circadian clock. PLoS One. Aug 12; 8(8): e70481. PMC3741311
Lee J.E, L. Zamdborg, B. Southey, N. Atkins, Jr., J.W. Mitchell, M. Li, M.U. Gillette, N.L. Kelleher, J.V. Sweedler. 2013. Quantitative peptidomics for discovery of circadian-related peptides from the rat suprachiasmatic nucleus. J. Proteome Res. 2013 Feb 1; 12(2): 585-93. PMCID #3562399
Wang, T.A., Y.V. Yu, G. Govindaiah, X. Ye, L. Artinian, T.P. Coleman, J.V. Sweedler, C.L. Cox, M.U. Gillette. 2012. Circadian rhythm of redox state non-transcriptionally regulates excitability in suprachiasmatic nucleus neurons. Science.337(6096): 839-42. http://www.sciencemag.org/content/337/6096/839.full.pdf Perspective: Circadian Time Reduxed. http://www.sciencemag.org/content/337/6096/805.full.pdf. PMCID #3490628
Millet, L.J. and M.U. Gillette. 2012. New perspectives on neuronal development using microfluidic environments. Trends in Neuroscience. 2012 Dec; 35(12): 752-61. PMCID # 3508261
Govindaiah G, T.A. Wang, M.U. Gillette, C.L. Cox. 2012. Activity-dependent regulation of retinogeniculate signaling by metabotropic glutamate receptors. J. Neuroscience 32(37): 12820-31. PMCID #3462222
Millet, L.J., M.U. Gillette. 2012. Over a century of neuron culture: From the hanging drop to microfluidic devices. Yale J. Biol. Med. 2012 Dec; 85(4): 501-21. PMCID #3516892
Yin P., A.M. Knolhoff, H.J. Rosenberg, L.J. Millet, M.U. Gillette, J.V. Sweedler. 2012. Peptidomics analysis of astrocyte secretion. J. Proteome Res. 2012 Aug 3; 11(8): 3965-73. PMCID #3434970
Cecala, C., S.S. Rubakhin, J.W. Mitchell, M.U. Gillette, J.V. Sweedler. 2012. A hyphenated optical trap capillary electrophoresis laser induced native fluorescence system for single-cell chemical analysis. Analyst. 137(13): 2965-72. PMCID #3558031
Murphy, David. A. Konopacka, C. Hindmarch, J.F.R. Paton, J.V. Sweedler, M.U. Gillette, Y. Ueta, V. Grinevich, M. Lozic, N. Japundzic-Zigon. 2012. The Hypothalamo-Neurohypophyseal System: from Genome to Physiology. J. Neuroendocrinol. 539-553. PMCID #3315060
Mitchell, J.W., N. Atkins, Jr., J.V. Sweedler, M.U. Gillette. 2011. Direct cellular peptidomics of hypothalamic neurons. Front. Neuroendocrinol. 32(4): 377-386. PMCID # 3165142
Millet, L. J., Jain, A., & Gillette, M. U. (2023). Less Is More: Oligomer Extraction and Hydrothermal Annealing Increase PDMS Adhesion Forces for Materials Studies and for Biology-Focused Microfluidic Applications. Micromachines, 14(1), . https://doi.org/10.3390/mi14010214
Gillette, M. U., & Mitchell, J. W. (2022). Electrophysiology of the Suprachiasmatic Nucleus: Single-Unit Recording. In Methods in Molecular Biology (pp. 181-189). (Methods in Molecular Biology; Vol. 2482). Humana Press Inc.. https://doi.org/10.1007/978-1-0716-2249-0_12
Kouzehgarani, G. N., Kandel, M. E., Sakakura, M., Dupaty, J. S., Popescu, G., & Gillette, M. U. (2022). Circadian Volume Changes in Hippocampal Glia Studied by Label-Free Interferometric Imaging. Cells, 11(13), . https://doi.org/10.3390/cells11132073
Norsworthy, M. D., & Gillette, M. U. (2022). Microfluidic Devices for Analysis of Neuronal Development. In Engineering Biomaterials for Neural Applications (pp. 169-185). Springer. https://doi.org/10.1007/978-3-031-11409-0_4
Kaufman, C. D., Liu, S. C., Cvetkovic, C., Lee, C. A., Naseri Kouzehgarani, G., Gillette, R., Bashir, R., & Gillette, M. U. (2020). Emergence of functional neuromuscular junctions in an engineered, multicellular spinal cord-muscle bioactuator. Bioengineering, 4(2), . https://doi.org/10.1063/1.5121440