Graduate Program in Cell & Developmental Biology

Circadian (~24 h) rhythmicity is an evolutionarily conserved property that regulates fundamental biological processes. Rhythmic gene expression is found in a variety of cells and tissues. In mammals, the master pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN relays photic information from the retina to the brain to synchronize endogenous rhythms to ambient light/dark cycles. Disruption of the circadian rhythm and body clock function is associated with many human diseases.

We are interested in mRNA translational control mechanisms that regulate the functions of the circadian clock and how dysregulated translational control is involved in circadian dysfunction in neurological and psychiatric diseases. We are particularly interested in the role of the mammalian target of rapamycin (mTOR) signaling and integrated stress response as the coupling mechanisms between cell metabolism and the circadian clock. We constantly look for talented and motivated undergraduates, graduate students, and postdoctoral researchers to join us.

Research Techniques:

Our laboratory utilizes a combination of molecular, cellular, and behavioral technologies, including polysome profiling, RNA sequencing, qRT-PCR, Western blotting, immunocytochemistry, electrophysiology, confocal microscopy, viral-mediated gene silencing and animal behavioral analysis (e.g., circadian, social and memory tests, EEG). A variety of model systems, including cell culture, organotypic slice culture, and whole animals (transgenic and knockout mice) are employed.

Publications

The Translational Stem Cell Neurobiology Laboratory studies brain disorders in which inhibitory interneuron function is compromised, such as schizophrenia, epilepsy, Alzheimer’s disease, neuropathic pains and autism spectrum disorders, with the aim of developing novel therapeutics for these debilitating disorders.

To find a better way to treat cortical interneuron-associated brain disorders,  we make inhibitory interneurons from induced pluripotent stem cells and study these patient neurons to understand their abnormalities. This study could lead to novel and more effective therapies for various interneuron-associated brains disorders such as schizophrenia and autism spectrum disorders.

In addition to studying disease mechanisms, we also develop interneuron cell therapy for various inhibitory interneuron-associated brain disorders. We have shown that transplantation of stem cell-derived human interneurons effectively reduce seizures and ameliorate cognitive deficits in animal models of epilepsy. We are further developing this novel therapeutics for the purpose of clinical translation.

Publications