ResearchOne 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 neuron and neural network, and they are believed to be responsible for governing behavioral and psychological functioning. Dr. Han’s laboratory is specifically interested in identifying the neural adaptations in the dopamine circuit of the ventral tegmental area that are induced by chronic stress and alcohol use. Research in Dr. Han’s laboratory focuses on the underlying mechanisms of these neuroadaptations and how they mediate behavioral susceptibility and resilience to chronic stress and alcohol use in rodent models for depression and alcohol dependence.
Our laboratory employs a “systematic research strategy” to study the nature of susceptibility and resilience from behavioral phenomenon to molecular mechanisms and back to the behavioral level, such that we will be able to identify the molecular, cellular and circuit adaptations that are both sufficient and necessary to underlie the behavioral phenomena. We use the chronic social defeat stress model of depression, (1) obtain a stable behavioral phenotype; (2) focus on VTA dopamine neurons; (3) find firing/bursting neuroadaptations in these neurons; (4) explore ionic/receptor mechanisms of the firing/bursting adaptations; (5) imitate or block the ionic or 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 a key that helps us to find right drug targets, in the extremely complicated brain, for depression treatment.
2021 - present, Principal Investigator, Center for Brain Cognition and Brain Disease, Institute of Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
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, Adjunct Professor, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York
2020 - present, Adjunct Professor, Department of Neuroscience and Friedman Brain Institute, 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,
[*Co-first author; †Corresponding authors]
- Han MH,Bolanos CA, Green TA, Olson VG, Neve RL, Liu RJ, Aghajanian GK and Nestler EJ: Role of cAMP response element-binding protein (CREB) in the rat locus coeruleus: Regulation of neuronal activity and opiate withdrawal behaviors. The Journal of Neuroscience, 26(17):4624-9, 2006.
- Krishnan V*, Han MH*, Graham DL, Berton O, Renthal W, Russo SJ, LaPlant Q, GrahamA, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green TA, Neve RL, Chakravarty S, Kumar A, Eisch AJ, Self DW, Lee FS, Tamminga C, Cooper DC, Gershenfeld HK and Nestler EJ: Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell, 131(2):391-404, 2007. [Cited over 1,800 times]
- Wallace DL*, Han MH*, Graham DL, Green TA, Vialou VF, Iñiguez SD, Cao JL, Chakravarty S, Kumar A, Krishnan V, Neve RL, Cooper DC, Bolanos CA, Barrot M, McClung CA and Nestler EJ: CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. Nature Neuroscience, 12(2):200-209, 2009.
- Cao JL, Covington III HE, Friedman AK, Wilkinson MB, Walsh JJ, Cooper DC, Nestler EJ and Han MH: Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action. The Journal of Neuroscience,30(49):16453-16458, 2010
- Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW, Ferguson D, Tsai HC, Pomeranz L, Christoffel D, Nectow AR, Ekstrand M, Domingos A, Mazie-Robison M, Mouzon E,Lobo MK, Neve RL, Friedman JM, Russo SJ, Deisseroth K, Nestler EJ and Han MH: Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature, 493(7433):532-6, 2013.
- Walsh JJ, Friedman AK, Sun H, Heller EA, Ku SM, Juarez B, Burnham VL, Mazei-Robison M, Ferguson D, Golden SA, Koo JW, Chaudhury D, Christoffel DJ, Pomeranz L, Friedman JM, Russo SJ, Nestler EJ and Han MH: Stress and CRF gate neural activation of BDNF in the mesolimibic reward pathway. Nature Neuroscience, 17(1):27-9, 2014.
- Friedman AK, Walsh JJ, Juarez B, Ku MS, Chaudhury D, Wang J, Li X, Dietz DM, Pan N, Vialou VF, Neve RL, Yue Z and Han MH: Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience. Science, 344(6181):313-9, 2014.
- Friedman AK,Juarez B, Ku SM, Zhang HX, Calizo RC, Walsh JJ, Chaudhury D, Zhang S, Hawkins A, Dietz DM, Murrough JW, Ribadeneira M, Wong EH, Neve RL and Han MH: KCNQ channel openers reverse depressive symptoms via an active resilience mechanism. Nature Communications, 7:11671, doi: 10.1038/ncomms11671, 2016.
- Calipari ES*, Juarez B*, Morel C, Walker DM, Cahill ME, Ribeiro E, Roman-Ortiz C, Ramakrishnan C, Deisseroth K, Han MH† and Nestler EJ†: Dopaminergic dynamics underlying sex-specific cocaine reward. Nature Communications, 8:13877, doi: 10.1038/ncomms13877, 2017.
- Juarez B, Morel C, Ku SM, Liu Y, Zhang H, Montgomery S, Gregoire H, Ribeiro E, Crumiller M, Roman-Ortiz C, Walsh JJ, Jackson K, Croote D, Zhu Y, Zhang S, Vendruscolo LF, Edwards S, Roberts A,Hodes G, Lu Y, Calipari ES, Chaudhury D, Friedman AK and Han MH: Midbrain circuit regulation of individual alcohol drinking behaviors in mice. Nature Communications, 2017 Dec 20; 8(1):2220. Doi:10.1038/s41467-017-02365-8, 2017.
- Tan A, Costi S, Morris LS, Van Dam NT, Kautz M, Whitton AE, Friedman AK, Collins KA, Ahle G, Chada N, Do B, Pizzagalli DA, Iosifescu DV, Nestler EJ, Han MHand 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, 2018 Nov 1. doi: 10.1038/s41380-018-0283-2, 2018.
- Zhang HX, Chaudhury D, Nectow AR, Friedman AK, Zhang S, Juarez B, Liu H, Pfau ML, Aleyasin H, C Jiang, Crumiller M, Calipari ES, Ku SM, Morel C, Tzavaras N, Montgomery SE, He M, Salton SR, Russo SJ, Nestler EJ, Friedman JM, Cao JL†and Han MH†: Alpha1 and beta3 adrenergic receptor-mediated mesolimbic homeostatic plasticity confers resilience to social stress in susceptible mice. Biological Psychiatry, 85(3):226-236, 2019.
- Costi S, Morris LS, Kirkwood KA, Hoch M, Corniquel M, Vo-Le B, Iqbal T, Chadha N, Pizzagalli DA, Whitton A, Bevilacqua L, Jha MK, Ursu S, Swann AC, Collins KA, Salas R, Bagiella E, Parides MK, Stern ER, Iosifescu DV, Han MH, Mathew SJ and Murrough JW: Impact of the KCNQ2/3 channel opener ezogabine on reward circuit activity and clinical symptoms in depression: results from a randomized controlled trial. The American Journal of Psychiatry, 2021 Mar 3: appiajp202020050653. doi: 10.1176/appi.ajp.2020.20050653, 2021.
- Haynes SH and Han MH: A novel role for hypothalamic AgRP neurons mediate depressive behavior. Trends in Neurosciences, 2021 Mar 2: S0166-2236(21)00037-0. doi: 10.1016/j.tins. 2021.02.005, 2021.