Affiliations
Assistant Member, Monell Chemical Senses Center
BrancoWeiss Fellow at Institute of Arctic Biology, University of Alaska Fairbanks
Education
Ph.D. Biochemistry and Structural Biology, University of California, Davis
Research Summary
Our lab investigates how brain circuits integrate environmental challenges with metabolic demands to shape survival behaviors across diverse animal models. We study this fundamental question through two complementary approaches: experimentally dissecting mechanisms in mice and examining natural adaptations in hibernating animals like arctic ground squirrels and bears. In mice, we have identified brain regions that act as critical hubs for sensing cold-induced energy expenditure and dynamically switching behavior between energy conservation and food seeking that demonstrates how neural circuits translate metabolic state into context-appropriate action. Hibernating animals push these brain-metabolism interactions to remarkable extremes. Arctic ground squirrels survive months at body temperatures below freezing, tolerate massive reductions in blood flow, and avoid the cellular damage that would destroy human tissues, yet emerge each spring with intact brain function. By studying how environmental pressures like extreme cold, starvation, and seasonal changes drive neural circuits to orchestrate metabolic resilience and protective responses, we aim to identify the molecular pathways and circuit mechanisms that enable survival under stress.
These discoveries have potential applications spanning neurological and metabolic diseases. We employ cutting-edge tools including stem cell models of human disease, optical and chemical circuit manipulation tools, whole-brain imaging, AI-driven behavioral analysis, and molecular profiling to understand how brains coordinate with the body’s metabolic systems. By bridging comparative physiology and systems neuroscience with biomedical research, we seek to translate nature’s evolutionary innovations into therapies that enhance human resilience to injury and disease.
Keywords
Neural circuits, Comparative physiology, Hibernation, Systems neuroscience, Cold adaptation, Obesity, Diabetes, Alzheimer’s disease
Representative Publications
Le, P., Lal, N., Xu, S. Mumford, S. Huang, M., Yang, D., Mizrahi, O., Hoover, B., Yee, B., Mei, Y.,
Rothamel, K., Her, H., Blue, S., Shneider, N., Yeo, G. KIF5A binds RNA to orchestrate synaptic mRNA localization and stress granules in ALS (Under Revision)
Lal N.K., Phuong Le, Samarth Aggarwal, Alan Zhang, Kristina Wang, Tianbo Qi, Zhengyuan Pang, Dong Yang, Victoria Nudell, Gene W. Yeo, Alexander S. Banks, Li Ye. Xiphoid nucleus of the midline thalamus controls cold-induced food seeking. Nature 621, 138–145 (2023). https://doi.org/10.1038/s41586-023-06430-9.
Lal N.K., Li Ye. Neural basis of why mammals eat more in the cold. Nature (2023). https://doi.org/10.1038/d41586-023-02384-0.
Nudell V#, Wang Y#, Pang Z, Lal N.K., Kanim W, Huang Min, Shaabani N, Teijaro J, Maximov A, and Ye L. HYBRiD: Hydrogel reinforced DISCO for clearing mammalian bodies. Nature Methods 19, 479–485 (2022). doi.org/10.1038/s41592-022-01427-0.
Lal N.K.*, Thanasuwat B., Huang P.J., Michelmore R.W., Dinesh-Kumar S.P*. Phytopathogen Effectors Use Multiple Mechanisms to Manipulate Plant Autophagy. Cell host & microbe 28, 558–571 e556 (2020). (*Co-Corresponding author)
