Wei Qi

All Publications

• Deconstruction of a spino-brain-spinal cord circuit that drives chronic pain. Nature Wang, Q., Lee, J. H., Nachtrab, G., Yuan, Y., Yuan, L., Qi, W., Mohr, M. A., Xiong, J., Horowitz, M. A., Chen, X. 2026

  Abstract

  Tissue inflammation or nerve injury at the periphery can cause chronic pain. Although the spinal-cord-projecting neurons in the rostral ventromedial medulla (RVMSC neurons) can promote pain chronification1-4, the pathway by which peripheral injury signals drive these neurons is poorly understood1-3,5. Here we report a circuit loop that extends from the spinal cord to the ventral posterolateral thalamus and posterior complex of the thalamus, proceeds to the primary somatosensory cortex and returns to the spinal cord via the lateral superior colliculus, which in turn connects to μ-opioid-receptor-expressing RVMSC neurons. Silencing any node along this multisynaptic circuit has minimal effects on nociception in healthy mice, but can eliminate mechanical hypersensitization and restore normal nociceptive response thresholds in mouse models of inflammatory and neuropathic pain. In healthy mice, repetitive-but not acute-activation of each node in this circuit is sufficient to cause robust chronic mechanical hypersensitization. Our findings reveal a spino-brain-spinal cord circuit loop that links ascending and descending pathways and specifically drives chronic mechanical pain. This could enable the identification of cellular targets for treating chronic pain.

  View details for DOI 10.1038/s41586-026-10296-y

  View details for PubMedID 41922770

  View details for PubMedCentralID 2964993

• Python metabolomics uncovers a conserved postprandial metabolite and gut-brain feeding pathway. Nature metabolism Xiao, S., Wang, M., Martin, T. G., Scott, B., Fang, X., Liu, X., Yang, Y., Fu, S., Truong, S. D., Gugel, J. F., Maas, G. L., Mullen, M. P., Hill, J. H., Li, V. L., Markhard, A. L., Zhao, M., Qi, W., Reghupaty, S. C., Zhao, M., Spaas, J., Wei, W., Moholdt, T., Hawley, J. A., Voldstedlund, C. T., Richter, E. A., Chen, X., Svensson, K. J., Bernstein, D., Leinwand, L. A., Xu, Y., Long, J. Z. 2026

  Abstract

  Most mammals consume small and frequent meals. By contrast, pythons are ambush predators that exhibit extreme feeding and fasting patterns and provide a unique model for uncovering molecular mediators of the postprandial response1-3. Using untargeted metabolomics, we show that circulating levels of the metabolite para-tyramine-O-sulphate (pTOS) are increased more than 1,000-fold in pythons after a single meal. In pythons, pTOS production occurs in a microbiome-dependent manner via sequential decarboxylation and sulphation of dietary tyrosine. In both pythons and mice, pTOS administration activates a neural population in the ventromedial hypothalamus (VMH). In mice, these VMH neurons are required for the anorexigenic effects of pTOS. Chronic administration of pTOS to diet-induced obese male mice suppresses food intake and body weight. pTOS is also present in human blood, where its levels are increased after a meal. Together, these data uncover a conserved postprandial anorexigenic metabolite that links nutrient intake to energy balance.

  View details for DOI 10.1038/s42255-026-01485-0

  View details for PubMedID 41857429

  View details for PubMedCentralID 3870669

• Sexual failure decreases sweet taste perception in maleDrosophilavia dopaminergic signaling. eLife Wang, G., Qi, W., Huang, R., Wang, L. 2025; 14

  Abstract

  Sweet taste perception, a critical aspect of the initiation of feeding behavior, is primarily regulated by an animal's internal metabolic state. However, non-metabolic factors, such as motivational and emotional states, can also influence peripheral sensory processing and hence feeding behavior. While mating experience is known to induce motivational and emotional changes, its broader impact on other innate behaviors, such as feeding, remains largely uncharacterized. In this study, we demonstrated that the mating failure of male fruit flies suppressed sweet taste perception via dopamine signaling in specific neural circuitry. Upon repetitive failure in courtship, male flies exhibited a sustained yet reversible decline of sweet taste perception, as measured by the proboscis extension reflex (PER) towards sweet tastants as well as the neuronal activity of sweet-sensing Gr5a+ neurons in the proboscis. Mechanistically, we identified a small group of dopaminergic neurons projecting to the subesophageal zone (SEZ) and innervating with Gr5a+ neurons as the key modulator. Repetitive sexual failure decreased the activity of these dopaminergic neurons and in turn, suppressed Gr5a+ neurons via Dop1R1 and Dop2R receptors. Our findings revealed a critical role for dopaminergic signaling in integrating reproductive experience with appetitive sensory processing, providing new insights into the complex interactions between different innate behaviors and the role of brain's reward systems in regulating internal motivational and emotional states.

  View details for DOI 10.7554/eLife.105094

  View details for PubMedID 40699890

• Achieving optical transparency in live animals with absorbing molecules. Science (New York, N.Y.) Ou, Z., Duh, Y. S., Rommelfanger, N. J., Keck, C. H., Jiang, S., Brinson, K., Zhao, S., Schmidt, E. L., Wu, X., Yang, F., Cai, B., Cui, H., Qi, W., Wu, S., Tantry, A., Roth, R., Ding, J., Chen, X., Kaltschmidt, J. A., Brongersma, M. L., Hong, G. 2024; 385 (6713): eadm6869

  Abstract

  Optical imaging plays a central role in biology and medicine but is hindered by light scattering in live tissue. We report the counterintuitive observation that strongly absorbing molecules can achieve optical transparency in live animals. We explored the physics behind this observation and found that when strongly absorbing molecules dissolve in water, they can modify the refractive index of the aqueous medium through the Kramers-Kronig relations to match that of high-index tissue components such as lipids. We have demonstrated that our straightforward approach can reversibly render a live mouse body transparent to allow visualization of a wide range of deep-seated structures and activities. This work suggests that the search for high-performance optical clearing agents should focus on strongly absorbing molecules.

  View details for DOI 10.1126/science.adm6869

  View details for PubMedID 39236186