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RESEARCH & DISCOVERIES

Current Projects

Social Isolation and Behavioral Alterations

Chronic social isolation and loneliness have profound impacts on public health. Though experimental manipulations have been widely applied to studying sleep/wakefulness and circadian regulation in animal models, how normal sleep is perturbed by social isolation and chronic stress is largely unknown. We previously reported that chronically isolated fruit flies exhibit sleep-loss accompanied by overconsumption of food. The observed behavioral changes induced by chronic social isolation are linked to neural activities in specific neural circuits in the Drosophila brain (Li et al., Nature 2021). These results resonate with anecdotal findings of loneliness-associated sleep difficulties and hyperphagia in humans, and present a mechanistic link between chronic social isolation, metabolism, and sleep, addressing a long-standing call for animal models focused on loneliness (Vora et al., Brain Science Advances 2022) . Currently, we are focusing on analyzing genetic pathways underlying chronic social isolation-induced sleep loss and determining how circadian, seasonal, disease, and age factors influence these pathways.

©Edvard Munch. Self Potrait between the Clock and the Bed, 1940-43.
Social Isolation Timer and Sleep Homeostat

The hemibrain dataset - the electron microscopy-based fully reconstructed synaptic-level connectome of the Drosophila central brain - theoretically predicted that a specific neuron type, hDeltaK, exhibits strong synaptic connections with the known sleep-wake network in Drosophila (Hulse et al., eLife 2021). We have determined that hDeltaK is the primary constituent of P2 neurons (Li et al., Nature 2021). Our work has provided the first experimental evidence that hDeltaK (P2 neurons) participates in sleep-wake networks in a peculiar way: it regulates chronic social isolation-induced sleep loss. We propose that these neurons act like an “isolation stopwatch” and contribute to the “isolation timing” during chronic social isolation. We are currently working on identifying neural substrates in hDeltaK, and neural circuits connecting with hDeltaK, which underlie social isolation-induced sleep loss using state-of-the-art genomics and imaging methods. These neural substrates and circuits will reveal: (a) principles of sleep and wakefulness control; (b) molecular and circuit mechanisms underlying the passage of time during chronic social isolation.

©Wanhe Li, 2022.
Chronic Stress and Cancer

We also seek to apply our findings in stress/behavior neurobiology to the field of chronic diseases, and ultimately to establish a genetically tractable model to study the reciprocal relationship between chronic stress and the progression of chronic illness, such as cancer. We are proudly supported by the Cancer Prevention and Research Institute of Texas (CPRIT) for developing this new and exciting direction of research.

©Wanhe Li, 2022.

Topics of interest to the lab include:

  • Chronic social isolation and loneliness 

  • Circadian clock

  • Sleep homeostasis

  • Hyperphagia (insatiable hunger) and metabolism  

  • Genetic models for tumorigenesis

  • Biological timing and timekeeping mechanisms

Approaches
we use:

  • Instrumentation

  • Behavioral neurogenetics

  • Neuroanatomy

  • Circuit tracing

  • 2-photon microscopy 

  • Genetics and genomics 

  • Quantitative genetics

  • Molecular and cellular biology

  • Deep learning-based behavioral analysis

  • Geospatial big data

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