Our laboratory is interested in the molecular and cellular mechanisms underlying pain and cognitive disorders. In our previous studies, we obtained the gene profiles of DRG affected by peripheral inflammation and peripheral nerve injury which often cause pathologic pain. We have identified fibroblast growth factor 13 (FGF13) and follistatin-like 1 etc to be new regulators of pain transmission, providing molecular and cellular basis for clinic analgesia and drug discovery. We have also found the interaction of different types of opioid receptors in primary sensory neurons, and have demonstrated its involvement in the tolerance of morphine analgesia, opening a direction for the function and drug research of receptor complex. Besides pain research, we discovered FGF13 as a microtubule-stabilizing protein to regulate the neuronal and brain development, providing a mechanism of the mental retardation induced by fgf13 deficiency. Our current projects focus on: 1) identification of new and important molecules involved in pain modulation and treatment; 2) analysis of genes related to mental retardation and their underlying mechanisms.
Identification of pain modulators and underlying mechanisms
Peripheral nerve injury and inflammation can induce pathological pain. A major interest in pain research is to identify pain modulators and mechanisms related to pathologic pain. Based on the idea that the change of gene expression in the spinal circuits could lead to chronic pain, we early developed rat cDNA arrays and demonstrated that the expression of the genes encoding channels, receptors and signal transduction-related molecules is strongly regulated in DRGs and the spinal dorsal horn after peripheral nerve injury. These studies provide evidences that peripheral nerve injury induces distinct gene profiles in both DRG and spinal dorsal horn. Recently, we developed single-cell RNA-seq technique on individual DRG neurons of adult mice to identify neuron types and their marker genes. Our current goals are: 1) to identify new and important molecules in pain modulation; 2) to determine the functions and neuronal circuits of identified DRG neuron types; 3) to explore the transcriptomic and functional changes in different DRG neuron types under pain condition; 4) to study the neuronal circuits of somatic sensation in central nerve system, and the effect of chronic pain on the structure and function of these circuits; 5) to study the cross-talk between pain circuit and other sensory circuits, and its role and underlying mechanism in cognitive functions and behaviors including learning and memory; 6) to identify new target, analgesic and technology for chronic pain treatment.
Identification of genes related to mental retardation and underlying mechanisms
Our study identified that FGF13 acted as a microtubule-stabilizing protein in the neurons and regulated the neuronal development and migration in the embryonic stage. This study provides an important mechanism for the development of brain functions including learning and memory and the mental retardation induced by fgf13 deficiency. Recently, we screened the gene mutations in children with mental retardation. And we prepared the cell and animal models to explore the genes, mutations and mechanisms related to mental retardation. Finally, we hope to develop the method and technology for early diagnosis and treatment of this disease.