Hailan Hu
Hu Hailan | |
|---|---|
| Born | 1973 Dongyang, Jinhua, Zhejiang, China |
| Occupation(s) | Neuroscientist, professor |
| Years active | 2002–present |
| Known for | Research on neural basis of social rank, depression, and ketamine's antidepressant effects |
Hu Hailan (; born 1973) is a distinguished Chinese neuroscientist serving as a professor and the executive director of the Center for Neuroscience at the Zhejiang University School of Medicine located in Hangzhou, China. Her scientific investigations primarily explore the neural foundations of social behaviors and psychiatric conditions, with a particular emphasis on the neural basis of social rank and the interactions between neurons and glial cells that contribute to depressive symptoms. Hu's groundbreaking work identified lateral habenular circuits in rodents as critical anatomical and molecular targets responsible for ketamine’s swift antidepressant effects. Notably, she was the first researcher from outside Europe and North America to be honored with the IBRO-Kemali Prize in more than two decades. Additionally, Hu holds membership in the Jiusan Society.
Early life and education
Born in 1973 in Dongyang, Jinhua, within Zhejiang province, Hu completed her undergraduate studies in biochemistry and molecular biology at Peking University in 1996.
Following this, she gained experience as a research technician at the University of California, San Francisco before enrolling in graduate school at University of California, Berkeley. Under the mentorship of Corey S. Goodman, Hu investigated how the plexin receptor and Rho family GTPases influence central nervous system development using Drosophila as a model organism. She pinpointed a crucial seven amino acid motif within PlexB necessary for Rac-GTP binding and axonal pathfinding, revealing that PlexB simultaneously suppresses Rac binding while activating RhoA to guide axon trajectories. Furthermore, Hu identified that CrossGAP, a GTPase-activating protein, modulates Rac-dependent cytoskeletal rearrangements during axon guidance. She earned her PhD in 2002.
After completing her doctorate, Hu pursued postdoctoral research with Julius Zhu and Roberto Malinow at the University of Virginia, followed by positions at Cold Spring Harbor Laboratory and the University of California, San Diego. Her research during this period centered on AMPA receptor trafficking’s role in memory consolidation and Ras GTPase signaling pathways associated with fragile X syndrome.
Career and research
In 2008, Hu returned to China to establish her laboratory as principal investigator at the Institute of Neuroscience under the Chinese Academy of Sciences in Shanghai. Her team investigates neural circuits underlying social hierarchy, depressive disorders, and mechanisms mediating ketamine’s antidepressant properties. By 2015, she was appointed professor and senior investigator at the Qiushi Academy for Advanced Studies, part of the School of Medicine at Zhejiang University in Hangzhou, where she also holds the position of executive director at the Center for Neuroscience.
Neural circuit foundations of social hierarchy
Hu’s laboratory has been at the forefront of investigating the neural pathways that determine social ranking. In 2011, their work revealed that neurons within the medial prefrontal cortex (mPFC) of mice carry information specific to social status. Mice with higher ranks exhibited strengthened excitatory synapses in mPFC pyramidal neurons. Adjusting this synaptic strength led to changes in the animals' positions within social hierarchies, underscoring the mPFC’s crucial function in regulating dominance.
Subsequent studies demonstrated that stimulating the dorsomedial prefrontal cortex (dmPFC) enhances success in social contests. Specifically, activation of medial dorsal thalamic (MDT) inputs to the dmPFC intensified dominant behaviors by promoting initiation of competition and increasing effort. These results identify mPFC circuits as central elements driving behaviors associated with social dominance.
Additionally, Hu’s group developed robust behavioral paradigms to evaluate social ranking, notably the "tube test," where two mice confront each other inside a narrow tube; the dominant individual forces the other out. When performed in a round-robin design over multiple days, this test reliably identifies consistent winners as dominant animals. This approach facilitates detailed examination of neural and biological factors underpinning social dominance.
Neural and glial contributions to depression
Hu and colleagues focus on neural circuit mechanisms underlying depressive states using rodent models. In 2013, they pinpointed the involvement of lateral habenula (LHb) circuits in depression, linked to increased expression of the enzyme BCamKII. This enzyme enhances excitatory synaptic transmission and neuronal firing by upregulating glutamate receptor levels, resulting in heightened habenular activity associated with depressive-like behaviors.
Further investigations employing proteomic techniques uncovered elevated levels of the astrocyte potassium channel Kir4.1 in rat models of depression, localized at synapses between astrocytes and neuronal cell bodies. Kir4.1 plays a pivotal role in controlling neuronal bursting and excitability within the LHb. Modulating Kir4.1 expression bidirectionally regulates neuronal hyperexcitability and depressive symptoms, emphasizing essential interactions between glial cells and neurons in psychiatric conditions.
The team also examined ketamine’s capacity to target LHb burst firing implicated in depression. Ketamine, recognized for its rapid antidepressant properties, inhibits NMDAR-dependent burst firing within the LHb, thereby reducing depressive symptoms in rodents. This suppression leads to disinhibition of downstream monoaminergic reward circuits, generating antidepressant effects through modulation of habenular pathways.
Awards and honors
- 2023 Asian Scientist 100, Asian Scientist
- 2022 L’Oréal-UNESCO For Women in Science International Awards
- 2019 Prize for Scientific and Technological Progress, Ho Leung Ho Lee Foundation
- 2019 IBRO-Kemali International Prize for research in basic and clinical neurosciences
- 2016 Tan Jia Zhen Life Science Award
- 2015 Chinese Young Female Scientist Award
- 2015 Chang Jiang Scholar Award
- 2015 L'Oréal-UNESCO For Women in Science
- 2013 Meiji Life Science Outstanding Award
- 2012 Chinese Outstanding Youth Award
- 2012 and 2014 Excellent Mentorship Award, Chinese Academy of Sciences
- 2010-2012 Shanghai Pujiang Talent Award
- 2009-2012 Chinese Hundred Talent Plan Award
- 2003-2006 Damon Runyon Foundation Postdoctoral Fellowship
- 2002 HHMI and IBRO fellowships for MBL Neurobiology Course
- 1998-2003 Howard Hughes Medical Institute Predoctoral Fellowship
Selected Publications
- Hu H, Cui Y, Yang Y. Functions and neural circuits of the lateral habenula in both health and pathological conditions. Nature Reviews Neuroscience. 2020.
- Gao Z, Hu H. Star-shaped cells trigger increased behavioral activity in mice. Nature. 2019.
- Cui Y, Hu S, Hu H. Targeting lateral habenular burst firing for the rapid antidepressant effects of ketamine. Trends in Neurosciences. 2019.
- Fan Z, Zhu H, Zhou T, et al. Employing the tube test to assess social hierarchy among mice. Nature Protocols. 2019.
- Cui Y, Yang Y, Dong Y, Hu H. Understanding depression: Contributions from glial cells and ketamine’s modulation of neuronal burst firing in the lateral habenula. Cold Spring Harbor Symposia On Quantitative Biology.
- Yang Y, Cui Y, Sang K, et al. Ketamine inhibits bursting activity in the lateral habenula to swiftly alleviate depressive symptoms. Nature. 2018.
- Cui Y, Yang Y, Ni Z, et al. Role of astroglial Kir4.1 in the lateral habenula in promoting neuronal bursts linked to depression. Nature. 2018.
- Zhou T, Zhu H, Fan Z, et al. Past victories reshape thalamo-prefrontal cortex circuitry to strengthen social dominance behaviors. Science. 2017.
- Wang F, Zhu J, Zhu H, et al. Synaptic efficacy in the medial prefrontal cortex bidirectionally regulates social hierarchy. Science. 2011.
- Hu H, Qin Y, Bochorishvili G, et al. Ras signaling pathways underlying deficits in GluR1-dependent synaptic plasticity related to fragile X syndrome. The Journal of Neuroscience. 2008.
- Hu H, Real E, Takamiya K, et al. Emotional states enhance learning through norepinephrine-mediated AMPA receptor trafficking regulation. Cell. 2007.
- Hu H, Marton TF, Goodman CS. Plexin B controls axon guidance in Drosophila by suppressing active Rac and promoting RhoA signaling pathways. Neuron. 2001.