Our laboratory focuses on understanding the genetic basis and molecular mechanisms of human disorders and aging. We are striving for EAF (Evolutionary analysis; Association study; Functional assay), to make research and life Easier And Fun.
Major research interests
We are interested in genetic basis and molecular mechanism of human diseases. Our current research is focused on two major directions:
(1) Onset risk factors and pathogenesis of Alzheimers' disease, schizophrenia, leprosy, and drug addiction;
(2) Biology of the Chinese tree shrew and animal models.
Following a simple thought that diseases are some kind of traits that were either fixed in the population (hereditary diseases) or occurred in the population as an acquired character (acquired diseases), and all these processes had their unique evolutionary history, we could decipher the genetic susceptibility and mechanism from an evolutionary medicine perspective. The disease causing mutations were accumulated on DNA sequences and were subjected to selection during the long time period. Similarly, the cross-talk and interactions between genes, pathways and environment reflected the adaptation to the past environment. Alteration of the current environment may cause unfitness to this ancient adaptation, as demonstrated by the fact that ancestral alleles might lead to the risk of common diseases in human populations. Therefore, reconstructing the evolutionary history of the risk alleles is crucial for us to decipher the mechanism of human disorders.
We will employ the next generation sequencing technique to perform genome-wide sequencing / whole exome sequencing analysis for patients with Alzheimer,s disease, schizophrenia, leprosy and related neuropsychiatric and neurological diseases.
Why we chose to analyze these diseases is that bacterial and viral infections and subsequent inflammation, and mitochondrial dysfunction played a key role in neurodegenerative diseases. Leprosy is a chronically infectious disease and neurological disorde, and can provide essential information for us to understand the abnormal communication between the immune system and the nervous system of the body during the onset of the disease. Schizophrenia and Alzheimer,s disease are neuropsychiatric disorders, and we speculate that the immune system genes and mitochondrial genes may be actively involved in the development of these diseases. We hope that by focusing on the neuroimmunology, we may find a new window to decipher the pathogenesis of these important diseases, which cause a heavy burden to the society, families and patients.
Meanwhile, we will carry out systematic studies to functionally characterize the putative pathogenic mutations that were distilled from the genome-wide assay. By overexpressing the mutant or knockdown the expression of the target gene at the cellular level, we attempt to uncover the role of target gene and characterize the pathway / regulation network. We have established a stable system for neuron differentiation from embryonic stem cells and induced pluripotent stem cell, and will use this system to analyze these genes involved in the neurological and neuropsychiatric diseases. On the other hand, we will use mouse, tree shrew and monkey to create related disease models, and perform in vivo assays.
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