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Li Ye

Li Ye, PhD

Assistant Professor, Department of Neuroscience
The Scripps Research Institute

Contact Information

Office Phone: 858-784-8081

The Scripps Research Institute
Dorris Neuroscience Center, Room 256
3528 General Atomics Ct
La Jolla, CA 92037

Lab Website

Research Description
The brain plays a pivotal role in integrating homeostatic signals and regulating whole-body metabolism. But the high energy demand of neurons also makes the CNS highly sensitive to systemic metabolic stress. We are interested in how the brain adapts to both acute and chronic metabolic changes and how such adaptation, in turn, affects the control of organismal physiology by the CNS, at the biochemical, cellular, and circuit levels. Our long-term goal is to harness the molecular and circuit mechanisms underlying these adaptations to target metabolic disorders including obesity and type 2 diabetes as well as certain neurodegenerative diseases.

We employ and design novel systems tools optimized for brain-wide structural mapping (whole-brain labeling, tissue clearing (“CLARITY”) and large-volume light-sheet imaging), in vivo multi-region Ca2+ imaging, and activity/connectivity-defined optogenetics. Based in TSRI, we also develop and apply high throughput screens (small molecules, genomic, proteomic, etc.) in conjunction with circuit-based tools to unleash the power of large scale unbiased screens in intact mammalian brains.

  • Kim CK,* Ye L*, Jennings JH, Pichamoorthy N, Tang DD, Wang AC, Ramakrishnan C, Deisseroth K. Molecular and Circuit-dynamical Identification of Top-down Neural Mechanisms for Restraint of Reward-seeking. Cell. 2017 Aug 24;170(5):1013-1027.e14.
  • Ye L*, Allen WE*, Thompson KR*, Tian Q, Hsueh B, Ramakrishnan C, Wang AC, Jennings JH, Adhikari A, Halpern CH, Witten IB, Barth AL, Luo L, McNab JA, Deisseroth K. Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences. Cell. 2016 Jun 16;165(7):1776-88. (Cover and Highlighted)
  • Lerner TN, Ye L, Deisseroth K. Communication in Neural Circuits: Tools, Opportunities and Challenges. Cell. 2016 Mar 10;164(6):1136-50 Tomer R, Ye L, Hsueh B, Deisseroth K. Advanced CLARITY for rapid and high-resolution imaging of intact tissues. Nat Protoc. 2014 Jul;9(7):1682-97
  • Cadavieco M*, Gorbati M*, Ye L, Kosse C, Börgers C, Veldt S, Lee SY, Ramakrishnan C, Denisova N, Ramm F, Hu Y, Bender F, Burdakov D, Deisseroth K, Ponomarenko A & Korotkova T. Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking. Nature. 2017 Feb 9;542(7640):232-236.
  • Ye L, Wu J, Cohen P, Kazak L, Khandekar MJ, Jedrychowski MP, Zeng X, Gygi SP and Spiegelman BM. Fat cells directly sense temperature to activate thermogenesis. Proc Natl Acad Sci U S A. July 1, 2013, 10.1073
  • Ye L, Kleiner S, Wu J, Sah R, Gupta RK, Banks AS, Cohen P, Khandekar MJ, Boström P, Mepani R, Laznik D, Kamenecka TM, Song X, Liedtke W, Mootha VK, Puigserver P, Griffin PR, Clapham DE and Spiegelman BM. TRPV4 is a regulator of adipose oxidative metabolism, inflammation and energy homeostasis. Cell. 2012 Sep 28;151(1):96-110.
  • Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang A, Khandekar M, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerbäck S, Schrauwen P and Spiegelman BM. Beige Adipocytes are a Distinct Type of Thermogenic Fat Cell in Mouse and Human. Cell. 2012 Jul 20;150(2):366-76.

  • (*co-first authors)