About

Martha U. Gillette is the Alumni Professor of Cell and Developmental Biology at the University of Illinois, with additional professorships in Neuroscience, Molecular and Integrative Physiology, Bioengineering, Biomedical and Translational Sciences, the Carl R. Woese Institute for Genomic Biology, and the Beckman Institute for Advanced Science and Technology. She holds a B.A. in Biology from Grinnell College, an M.S. in Zoology from the University of Hawaii, a Ph.D. in Zoology from the University of Toronto, and completed postdoctoral training at the University of California-Santa Cruz. Her research centers on the neurobiology of time, engineering neuronal development and repair, and the emergent behaviors of integrated neuronal systems. Gillette's work focuses on understanding the signals that engage the circadian clock in the brain, the sub-cellular micro-environments that shape neuronal dendrites during development and repair, and the behaviors of neuronal clusters. She investigates the central role of the brain's circadian clock, located in the suprachiasmatic nucleus (SCN), in organizing body functions around the daily cycle of light and darkness, which has broad implications for health and disease resistance. Her research explores how malfunctioning of the circadian clock contributes to clinical disorders such as sleep disturbances, movement disorders, and neurodegenerative diseases including Alzheimer's and Parkinson's. Additionally, Gillette's neuroengineering research aims to discover novel insights and applications for neural repair by studying the molecular signals that guide neuronal outgrowth and network formation. She also studies the control of microenvironments to understand and direct neuronal sensing, integration, and actuation properties. Her work integrates molecular and cellular biology, nano-scale analytical chemistry, and bioengineering to advance understanding of brain function and develop strategies to ameliorate neurological and cognitive disorders.

Research topics

• Neuroscience
• Computer Science
• Artificial Intelligence
• Medicine
• Biology
• Anatomy
• Materials science
• Biomedical engineering
• Physical medicine and rehabilitation
• Nanotechnology
• Internal medicine
• Engineering
• Cell biology
• Electrical engineering
• Endocrinology
• Genetics

Selected publications

• Label-free super-multiplex multiphoton imaging microscopy (Conference Presentation)

  2025-03-20

  article

  Multiphoton fluorescence microscopy is a powerful tool for revealing complex biological systems with high contrast, minimal out-of-focus bleaching, and deep penetration. However, clinical application faces challenges like the need for stable, tunable laser sources, comprehensive biological information, phototoxicity, and developing universal quality control tools. We developed a new generation label-free super-multiplex multiphoton imaging microscopy, enabling co-registered label-free 4-photon (tryptophan), 3-photon (NAD(P)H), 2-photon (FAD, porphyrin/lipofuscin), second harmonic (collagen), third harmonic (optical heterogeneity), and fluorescence lifetime imaging with single-shot, single-band excitation near 1110 nm. Our laser source features tunable wavelength (950-1150 nm), pulse repetition rate (1-10 MHz), and pulse width (40-400 fs), with stability over 2000 hours. We revealed phototoxicity mechanisms in nonlinear imaging, identified safe imaging parameters, and developed a universal tool for objective imaging performance comparison. This system maximizes fluorescence microscopy information while minimizing harm, paving the way for clinical translation.

  PublisherDOI

• Assessing Glymphatic Flow Modulation by Vasopressin and Relcovaptan Using Glymph-FIT: a Novel Approach with DCE-MRI

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article

  Motivation: Glymphatic flow is vital for clearing brain waste, which has implications for neurodegenerative diseases. A precise fitting tool is needed to provide sensitive measures of flow with vasopressin receptor modulation, so we designed Glymp-FIT. Goal(s): To assess relcovaptan's impact on very slow glymphatic flow and validate Glymph-FIT, our custom-designed gamma PDF-based DCE-MRI model, for accurately capturing dynamic flow changes. Approach: Using Glymph-FIT, we visualized glymphatic flow following relcovaptan administration, obtaining detailed temporal and spatial measurements. Results: Findings indicate that relcovaptan, as an antagonist, unexpectedly increases glymphatic flow, comparable to arginine vasopressin (AVP), which promotes V1A, V1B, and V2, suggesting indirect receptor activation effects. Impact: This study introduces Glymph-FIT, a novel tool for accurately measuring very slow glymphatic flow dynamics. Findings suggest V1A antagonism with relcovaptan enhances glymphatic flow, potentially offering new therapeutic strategies to improve brain waste clearance and potentially mitigate neurodegenerative disease progression.

  PublisherDOI

• Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems

  Cell Systems · 2025-12-01

  articleOpen access
  PublisherOA PDFDOI

• Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle

  Proceedings of the National Academy of Sciences · 2024 · 36 citations

  • Biology
  • Internal medicine
  • Neuroscience

  Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.

  PublisherOA PDFDOI

• Supercontinuum intrinsic fluorescence imaging heralds free view of living systems

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-26 · 3 citations

  preprintOpen access

  Optimal imaging strategies remain underdeveloped to maximize information for fluorescence microscopy while minimizing the harm to fragile living systems. Taking hint from the supercontinuum generation in ultrafast laser physics, we generated supercontinuum fluorescence from untreated unlabeled live samples before nonlinear photodamage onset. Our imaging achieved high-content cell phenotyping and tissue histology, identified bovine embryo polarization, quantified aging-related stress across cell types and species, demystified embryogenesis before and after implantation, sensed drug cytotoxicity in real-time, scanned brain area for targeted patching, optimized machine learning to track small moving organisms, induced two-photon phototropism of leaf chloroplasts under two-photon photosynthesis, unraveled microscopic origin of autumn colors, and interrogated intestinal microbiome. The results enable a facility-type microscope to freely explore vital molecular biology across life sciences.

  PublisherOA PDFDOI

• Neurochemical and Morphological Comparisons of Motor Nerve Organoids and Spinal-Cord Explants

  ACS Chemical Neuroscience · 2024-12-18

  articleOpen access

  Organoids are multicellular structures formed in vitro from populations of individual cells allowing modeling of structural and functional aspects of organs and tissues in normal and diseased states. They offer unique opportunities to model and treat disease. Using a mouse embryonic stem cell line, we have cultured organoids that express markers of spinal cord motor neurons as well as motor neurons found within the peripheral nervous system. The morphology and select neurotransmitter content of the organoids and spinal cord explants were compared at different developmental time points. We found indications of maturation in the organoids over time, mirrored by similar trends in the spinal cord explants. Although the organoids contained the same neurotransmitters as the spinal cord explants, the developmental changes of these neurotransmitter levels were less marked in organoids. Given these differences, further work is required to optimize organoid growth conditions to better reproduce in vivo models when using organoids to study development.

  PublisherOA PDFDOI

• Disrupted sleep, disrupted metabolism: A potential link between circadian rhythms and tumorigenesis

  Brain Behavior and Immunity Integrative · 2024-07-01

  articleOpen accessSenior authorCorresponding
  PublisherDOI

• Less Is More: Oligomer Extraction and Hydrothermal Annealing Increase PDMS Adhesion Forces for Materials Studies and for Biology-Focused Microfluidic Applications

  Micromachines · 2023-01-14 · 5 citations

  articleOpen accessSenior authorCorresponding

  Cues in the micro-environment are key determinants in the emergence of complex cellular morphologies and functions. Primary among these is the presence of neighboring cells that form networks. For high-resolution analysis, it is crucial to develop micro-environments that permit exquisite control of network formation. This is especially true in cell science, tissue engineering, and clinical biology. We introduce a new approach for assembling polydimethylsiloxane (PDMS)-based microfluidic environments that enhances cell network formation and analyses. We report that the combined processes of PDMS solvent-extraction and hydrothermal annealing create unique conditions that produce high-strength bonds between solvent-extracted PDMS (E-PDMS) and glass—properties not associated with conventional PDMS. Extraction followed by hydrothermal annealing removes unbound oligomers, promotes polymer cross-linking, facilitates covalent bond formation with glass, and retains the highest biocompatibility. Herein, our extraction protocol accelerates oligomer removal from 5 to 2 days. Resulting microfluidic platforms are uniquely suited for cell-network studies owing to high adhesion forces, effectively corralling cellular extensions and eliminating harmful oligomers. We demonstrate the simple, simultaneous actuation of multiple microfluidic domains for invoking ATP- and glutamate-induced Ca2+ signaling in glial-cell networks. These E-PDMS modifications and flow manipulations further enable microfluidic technologies for cell-signaling and network studies as well as novel applications.

  PublisherOA PDFDOI

• Development of circadian neurovascular function and its implications

  Frontiers in Neuroscience · 2023-09-05 · 8 citations

  reviewOpen accessSenior authorCorresponding

  The neurovascular system forms the interface between the tissue of the central nervous system (CNS) and circulating blood. It plays a critical role in regulating movement of ions, small molecules, and cellular regulators into and out of brain tissue and in sustaining brain health. The neurovascular unit (NVU), the cells that form the structural and functional link between cells of the brain and the vasculature, maintains the blood-brain interface (BBI), controls cerebral blood flow, and surveils for injury. The neurovascular system is dynamic; it undergoes tight regulation of biochemical and cellular interactions to balance and support brain function. Development of an intrinsic circadian clock enables the NVU to anticipate rhythmic changes in brain activity and body physiology that occur over the day-night cycle. The development of circadian neurovascular function involves multiple cell types. We address the functional aspects of the circadian clock in the components of the NVU and their effects in regulating neurovascular physiology, including BBI permeability, cerebral blood flow, and inflammation. Disrupting the circadian clock impairs a number of physiological processes associated with the NVU, many of which are correlated with an increased risk of dysfunction and disease. Consequently, understanding the cell biology and physiology of the NVU is critical to diminishing consequences of impaired neurovascular function, including cerebral bleeding and neurodegeneration.

  PublisherOA PDFDOI

• Microfluidic Devices for Analysis of Neuronal Development

  2022-01-01 · 1 citations

  book-chapterSenior author
  PublisherDOI

Recent grants

• NIH Grant R01NS033240

  NIH · $787k · 2000

• NIH Grant R01HL086870

  NIH · $1.6M · 2013

• NIH Grant R01HL092571

  NIH · $967k · 2012

• High Resolution Analysis of miR125b in Dendrites via Microfluidic Devices

  NIH · $436k · 2013–2016

• NIH Grant R01NS022155

  NIH · $4.6M · 2006

Frequent coauthors

• Jonathan V. Sweedler

  University of Illinois Urbana-Champaign

  59 shared

• Hyunjoon Kong

  University of Illinois Urbana-Champaign

  39 shared

• Jian Ding

  Wannan Medical College

  28 shared

• Larry J. Millet

  University of Tennessee at Knoxville

  28 shared

• Gabriel Popescu

  28 shared

• Jennifer W. Mitchell

  University of Illinois Urbana-Champaign

  25 shared

• Gordon F. Buchanan

  University of Miami

  19 shared

• Rhanor Gillette

  University of Illinois Urbana-Champaign

  15 shared

Labs

• The Clockworks LabPI

Awards & honors

• NSF BRAIN EAGER (2014-17)
• NIH BRAIN Innovation Award (2015-18)
• Women in Neuroscience Lifetime Achievement Award
• AAAS Fellow