Diseases of the nervous system, ranging from epilepsy, stroke, and Alzheimer's disease, which affect millions, to rare ones such as Rett's Syndrome and Rasmussen's Encephalitis, have devastating consequences for individuals of all ages and represent increasing medical and socioeconomic problems. Although symptomatic treatments are available in some diseases, mechanism-based therapies to prevent or cure these diseases are lacking. The long-term Research Interests of our laboratory are to understand the molecular and cellular mechanisms of neurological diseases, especially those relating to mental retardation and epilepsy.
Ongoing Projects:
Molecular and genetic mechanisms of mental retardation
Mental retardation is a cognitive disability characterized by significant limitations both in intellectual abilities and in adaptive behaviors such as conceptual, social, and practical skills. It occurs naturally in 2%-3% of the population, as results of injury, disease, or genetics. Mutations in X-linked genes are important causes of mental retardation. Several genes associated with mental retardation have been identified, such as fmr1 in Fragile X Syndrome, mecp2 and stk9 in Rett’s syndrome and ube3a in Angelman Syndrome. However, the molecular pathways that lead from the genetic mutations to mental retardation are not clear. We would like to propose that “mental retardation” genes contribute to neuronal morphogenesis and synaptic plasticity. We will use molecular biology, electrophysiological and imaging techniques in cultured neurons and knock-out mouse models to investigate how these genes affect neuronal development and functioning.
Molecular and circuit mechanism of epilepsy
The incidence of epilepsy is about 1-2%, with a higher proportion in children. About 35%-40% of children with epilepsy are also accompanied by mental disorders. Brain injuries such as stroke, brain trauma, high fever convulsions, meningitis, encephalitis, or related developmental diseases can cause epilepsy. The mechanism of epileptic occurrence is not clear, and there are no effective preventive or theraputical treatments. Existing drugs can only relieve the symptoms of epilepsy, but can not eradicate the lesion. Epileptic seizures are characterized by high excitability and high synchronicity of neuronal activity, and the abnormal behavior of this neuron is generally considered to be a permanent plasticity change caused by damage to normal functional brain tissue. Through the study of the mechanism of epilepsy at the molecular level, it can provide a new strategies or drug targets for the clinical treatment of epilepsy. At the same time, the progression of epilepsy is accompanied by changes in neuroplasticity, excitability, as well as neuronal damage, repair and regeneration, thus, by unveiling the underlying mechanisms, it can also provide fundamental basis for other neurodegenerative disorders, and help us to further understand the function of the brain. Epilepsy is often accompanied by degenerative lesions of neurons. Studies have shown that overactive NMDA receptors can cause neurons loss, but the causal relationship between epilepsy and neurodegenerative lesions, and whether the anti-epileptic effects of NMDA receptor antagonists come from their neuroprotective effects are still controversial. NMDA receptors have different subtypes, so we will study the role of different subtypes of NMDA receptors in the occurrence of epilepsy.
Modeling neurological disorders in non-human primates
Compared with other animal models, non-human primates and humans have greater similarities in metabolic immunity, anatomy and gene networks. Our primate platform has successfully mastered cloned monkey technology, and if combined with new gene editing techniques, various types of genetically modified neural disease monkey models can be constructed. These models will greatly promote the study of the mechanism of neurological diseases. The research on various metabolites, immune groups, brain imaging, neural loop function and behavior in the onset cycle of these disease monkey models will greatly promote the discovery and application of early diagnosis biomarkers, and then promote the drug treatment and physical intervention of neurological diseases research and development. We are working with various platforms to establish monkey models of hereditary neurological disorders (Alzheimer's disease, Parkinson's disease and intellectual developmental disorder cloned monkeys) and methamphetamine addiction and obsessive-compulsive macaque models, based on these models to conduct cognitive behavioral evaluation paradigms, in body electrophysiological records and research into the development of physical intervention methods.
Senior Investigator
