- Gastrointestinal motility and disorders
- Circadian rhythm and melatonin
- Congenital gastrointestinal and neural anomalies
- Diet and metabolism studies
- Dietary Effects on Health
- Neuroendocrine regulation and behavior
- Photoreceptor and optogenetics research
- Digestive system and related health
- Helicobacter pylori-related gastroenterology studies
- Infant Nutrition and Health
- Spaceflight effects on biology
- Neurobiology and Insect Physiology Research
- Advanced Materials and Mechanics
- Axon Guidance and Neuronal Signaling
- Intestinal Malrotation and Obstruction Disorders
- Neuroscience and Neuropharmacology Research
- Sleep and Wakefulness Research
- Advanced Sensor and Energy Harvesting Materials
- Neurological disorders and treatments
- Neurogenesis and neuroplasticity mechanisms
- Clinical Nutrition and Gastroenterology
- Gut microbiota and health
Neurosciences Institute
2021-2025
Stanford University
2019-2025
MRC Laboratory of Molecular Biology
2016-2020
Medical Research Council
2016
In mammals, endogenous circadian clocks sense and respond to daily feeding lighting cues, adjusting internal ∼24 h rhythms resonate with, anticipate, external cycles of day night. The mechanism underlying entrainment time is critical for understanding why mistimed feeding, as occurs during shift work, disrupts physiology, a state that associated with increased incidence chronic diseases such type 2 (T2) diabetes. We show feeding-regulated hormones insulin insulin-like growth factor 1 (IGF-1)...
The suprachiasmatic nucleus (SCN) is the master circadian clock controlling daily behavior in mammals. It consists of a heterogeneous network neurons, which cell-autonomous molecular feedback loops determine period and amplitude oscillations individual cells. In contrast, circuit-level properties coherence, synchrony, ensemble are determined by intercellular signals embodied wave gene expression that progresses across SCN. How mechanisms interact timekeeping poorly understood. To explore...
Abstract The hypothalamic suprachiasmatic nuclei (SCN) are the principal mammalian circadian timekeeper, co-ordinating organism-wide daily and seasonal rhythms. To achieve this, cell-autonomous timing by ~20,000 SCN cells is welded into a tight circuit-wide ensemble oscillation. This creates essential, network-level emergent properties of precise, high-amplitude oscillation with tightly defined period phase. Although synchronised, regional cell groups exhibit differentially phased activity,...
Abstract The suprachiasmatic nucleus (SCN) co-ordinates circadian behaviour and physiology in mammals. Its cell-autonomous oscillations pivot around a well characterised transcriptional/translational feedback loop (TTFL), whilst the SCN circuit as whole is synchronised to solar time by its retinorecipient cells that express release vasoactive intestinal peptide (VIP). circuit-level mechanisms whereby VIP synchronises are poorly understood. We show slices organotypic culture demonstrate rapid...
The organization and cellular composition of tissues are key determinants their biological function. In the mammalian gastrointestinal (GI) tract, enteric nervous system (ENS) intercalates between muscular epithelial layers gut wall can control GI function independent central (CNS) input.1 As in CNS, distinct regions tract highly specialized support diverse functions, yet regional spatial ENS remains poorly characterized.2 Cellular arrangements,3,4 circuit connectivity patterns,5,6 cell...
Abstract The enteric nervous system (ENS) plays an important role in coordinating gut function. ENS consists of extensive network neurons and glial cells within the wall gastrointestinal tract. Alterations neuronal distribution, function, type are strongly associated with neuropathies (GI) dysfunction can serve as biomarkers for disease. However, current methods assessing counts distribution suffer from undersampling. This is partly due to challenges imaging analyzing large tissue areas,...
The enteric nervous system (ENS) consists of an extensive network neurons and glial cells embedded within the wall gastrointestinal (GI) tract. Alterations in neuronal distribution function are strongly associated with GI dysfunction. Current methods for assessing suffer from undersampling, partly due to challenges imaging analyzing large tissue areas, operator bias manual analysis. We present Gut Analysis Toolbox (GAT), image analysis tool designed characterization their neurochemical...
Accurately reporting the identity and representation of enteric nervous system (ENS) neuronal subtypes along length gastrointestinal (GI) tract is critical to advancing our understanding ENS control GI function. Reports varying proportions subtype marker expression have employed different dissection techniques achieve wholemount muscularis preparations myenteric plexus. In this study we asked whether differences in methods could introduce variability into quantification expression.We...
Circadian (approximately daily) rhythms pervade mammalian behavior. They are generated by cell-autonomous, transcriptional/translational feedback loops (TTFLs), active in all tissues. This distributed clock network is coordinated the principal circadian pacemaker, hypothalamic suprachiasmatic nucleus (SCN). Its robust and accurate time-keeping arises from circuit-level interactions that bind its individual cellular clocks into a coherent time-keeper. Cells express neuropeptide vasoactive...
Abstract Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, ability incorporate various functionalities such as sensing stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, low density active components. These limitations stem the difficulty many components on one-dimensional (1D) fiber incompatibility conventional microfabrication methods (e.g., photolithography) with curved,...
Abstract Background Accurately reporting the identity and representation of enteric nervous system (ENS) neuronal subtypes along length gastrointestinal (GI) tract is critical to advancing our understanding ENS control GI function. Reports varying proportions subtype marker expression have employed different dissection techniques achieve wholemount muscularis preparations myenteric plexus. In this study, we asked whether differences in methods could introduce variability into quantification...
Abstract The enteric nervous system (ENS) controls digestion autonomously via a complex neural network within the gut wall. Enteric neurons expressing glutamate have been identified by transcriptomic studies as distinct subpopulation, and can affect intestinal motility modulating neuron activity. However, nature of glutamatergic neurons, their position ENS circuit, function in regulating are unknown. Here, we identify longitudinally projecting descending interneurons small intestine colon,...
Abstract The enteric nervous system (ENS) populates the gastrointestinal (GI) tract and controls GI function. In contrast to central system, macrostructure of ENS has been largely overlooked. Here, we visually computationally demonstrate that is organized in circumferential stripes regionally differ development neuronal composition. This characterization provides a blueprint for future understanding region-specific function identifying structural correlates disorders.
Abstract Circadian (∼daily) rhythms pervade mammalian behaviour. They are generated by cell-autonomous, transcriptional/translational feedback loops (TTFL), active in all tissues. This distributed clock network is co-ordinated the principal circadian pacemaker, hypothalamic suprachiasmatic nucleus (SCN). Its robust and accurate time-keeping arises from circuit-level interactions that bind its individual cellular clocks into a coherent time-keeper. Cells express neuropeptide vasoactive...