Research Interest

Major Depression and Antidepressant actions
Major depressive disorder (MDD) is the most prevalent mental illness and affects up to 20 % of the population worldwide . It is a chronic, recurrent, and even life-threatening mental disease . It is one of the major causes of morbidity and mortality, and it has become an increasingly greater health, social and economic burden. Still, current therapeutics has been largely limited to treat this disease timely and effectively without unnecessary side effects. Despite intense research over several decades, our understanding of the pathophysiology of this disease, as well as the anti-depressive mechanism of the current therapeutics, has remained elusive.

Mood disorders are largely associated with structural abnormalities within interconnected brain regions and networks implicated in depression suggesting that changes in information processing are a key component of these disorders. Many post-mortem neuroimaging studies of depressed patients have reported reductions in grey-matter volume and glial density in the hippocampus and prefrontal cortex. There is also persuasive evidence for several possible mechanisms, including neuronal plasticity, hippocampal neurogenesis, and expression of genes related to plasticity and resilience. Plasticity in neuronal networks has been well characterized during formation of memories and learning and modulation of such networks in the hippocampus has been characterized during stress, depression, and by antidepressant drugs. Currently, neuroplastic changes are believed to be responsible not only for the precipitation of major depression, but also for its reversal by chronic antidepressant medications. However, little is known about the neurobiological and structural changes underlying the mental illness and its reversal by anti-depressive medications.
 Our research interest focuses on the molecular mechanisms mediating either the abnormal or the beneficial changes in the neural circuit for mood regulation. Through molecular biological, genetic, and genomic approaches, we currently aim to identify the key molecules, neural cell types and their roles in the context of neural circuitry modulation. Our study will help delineate the molecular and cell-type specific mechanisms of depression and antidepressant action, and will instruct and inform the development of novel therapeutic agents with better therapeutic outcomes.

Long Term Goal of Our Projects

->Elucidation of neurobiological mechanisms underlying psychiatric disorders and therapeutics.

Specific Aims:
1. Cell-type specific transcriptional responses to chronic stress exposure and antidepressant medications
2. Molecular basis underlying neuroadaptive changes for major depression and its reversal by antidepressants
3. Illumination of neuroadaptive changes of each cell type within neural circuitry during stress-induced depression and its reversal by antidepressants
4. Genomic anatomy to understand functional heterogeneity of a neuronal cell type in normal and pathological conditions.