Professor Ming-Hu Han has long been dedicated to research on neuropsychiatric disorders. His work elucidates the neural mechanisms underlying individual variations inresponseto stress, addressing why some individuals develop depression under chronic stress (susceptibility) while others maintain mental and physical health (resilience). His discoveries include active self-regulatory mechanisms that promote resilient phenotype.

Professor Han has published over 20 papers in top-tier journals such as Nature, Science, Cell, and Nature Neuroscience, with atotal ofmore than 100 publications. His collaborative 2007 Cell study established a classic animal model for susceptibility and resilience research in the field and uncovered the determinant role of the firing activity of ventral tegmental area (VTA) dopamine neurons for these behavioral phenotypes, recognized by Nature as one of the year's 20 most significant papers.

One of the most fundamental functions of the brain is the capacity to develop adaptive changes in response to environmental stimuli under both physiological and pathophysiological conditions. These neural adaptations can occur at a variety of levels such as at the levels of ion channels, synaptic transmission, and integrative function of a neuron and neural network. They are believed to be responsible for governing behavioral and psychological functioning. Dr. Han’s laboratory is specifically interested in investigating the neural adaptations in the dopaminergic circuit of the VTA that are induced by chronic social stress and alcohol use. Research in Dr. Han’s laboratory focuses on the mechanisms underlying these adaptations and how they mediate behavioral susceptibility and resilience to chronic stress and alcohol use in rodent models for depression, anxiety and alcohol dependence.

Dr. Han’s laboratory employs a “systematic research strategy” to study the nature of susceptibility and resilience from behavioral phenotypes to molecular mechanisms and back to the behavioral level, such that the laboratory would be able to identify the molecular, cellular and circuit adaptations that are both sufficient and necessary to underlie the behavioral phenotypes. For instance, the laboratory uses a chronic social defeat stress (CSDS) model for depression, (1) obtain stable behavioral phenotypes; (2) focus on VTA dopamine neurons; (3) find firing adaptations in these dopamine neurons; (4) explore ionic/receptor mechanisms of the firing adaptations; (5) imitate firing adaptations in VTA dopamine neurons by molecular manipulations using viral-mediated gene transfer and optogenetic tools; and (6) further analyze key behavioral endpoints with these molecular manipulations in vivo. This “systematic research strategy” is the key that helps the laboratory to find right drug targets,including KCNQ and HCN channelsin the brain, for depression treatment.KCNQ channel openers have now been investigated in patients with major depressive disorder, and show significant antidepressantefficacyin those tested patients.

2021 - present, Chair Professor and Department Head,Department of Mental Health and Public Health,Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences

2021 - present, Principal Investigator, Center for Brain Cognition and Brain Disease, Institute of Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences

2021 - present, Adjunct Professor, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York

2017 - 2021, Deputy Director, Center for Affective Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York

2016 - 2021, Leader, Center of Excellence in Neuropharmacology, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York

2010 - 2021, Graduate Faculty, the Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York

01/1999, Ph.D. Neurobiology, Shanghai Institute of Physiology, Chinese Academy of

Sciences, Shanghai, China

04/1993, M.S. Image Processing and Pattern Recognition, South China University of

Technology, Guangzhou, China,

07/1983, B.S. Computer Science, Shenyang Institute of Technology, Shenyang, China,

1. Krishnan V#, Han MH#, et al., Nestler EJ*. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell, 2007;131:391-404.

2. Chaudhury D#, Walsh JJ#, et al., Han MH*. Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature, 2013;493:532-536.

3. Walsh JJ, et al., Han MH*. Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway. Nature Neuroscience, 2014;17:27-29.

4. Friedman AK, et al., Han MH*. Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience. Science, 2014;344:313-319.

5. Friedman AK, et al., Han MH*. KCNQ channel openers reverse depressive symptoms via an active resilience mechanism. Nature Communications, 2016;7:11671.

6. Calipari ES#, Juarez B#, et al., Han MH*, Nestler EJ*. Dopaminergic dynamics underlying sex-specific cocaine reward. Nature Communications, 2017;8:13877.

7. Juarez B, et al., Han MH*. Midbrain circuit regulation of individual alcohol drinking behaviors in mice. Nature Communications, 2017;8(1):2220.

8. Zhang HX, et al., Cao JL*, Han MH*. α1 and β3 adrenergic receptor-mediated mesolimbic homeostatic plasticity confers resilience to social stress in susceptible mice. Biological Psychiatry, 2019;85:226-236.

9. Tan A, et al., Han MH, Murrough JW*. Effects of the KCNQ channel opener ezogabine on functional connectivity of the ventral striatum and clinical symptoms in patients with major depressive disorder. Molecular Psychiatry, 2020;25:1323-1333. Clinical Trial.

10. Morel C*, et al., Han MH*. Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors. Nature Communications, 2022;13:1532.

Han Y#, Ai L#, Song L#, Zhou Y#, et al., Han MH*, Cao JL* and Zhang H*: Midbrain glutamatergic circuit mechanism of resilience to socially transferred allodynia in male mice. Nature Communications, 2024;15:4947