Regenerative Medicine

— Dr. Xue-Jun Li’s group

Human pluripotent stem cells, including both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have the capacity to become all cell types in the body, including neurons. They thus provide an invaluable tool for studying early human neural development and exploring the potential treatment of neurological diseases.

One of the research focuses in my lab is to specify neuronal subtypes from human pluripotent stem cells. In particular, we are interested in motor neurons whose degeneration underlies many debilitating diseases. By applying a set of morphogens in specific time windows, we have previously established a unique paradigm to efficiently generate spinal motor neurons from hESCs. Another type of motor neuron, cortical motor neuron, is specified by a very different mechanism than spinal motor neurons. By combining intrinsic and extrinsic factors, my group aims to establish a system to generate currently unavailable human cortical motor neurons. I also seek to build 3-dimensional neural tissue co-culture models to study the specification of cortical neuronal subtypes and the connection between cortical and spinal motor neurons

The other focus of my research is to use human pluripotent stem cells to model motor neuron diseases, major causes for disabilities. My group has successfully established both hESC- and iPSC-based models for spinal muscular atrophy (affecting spinal motor neurons) and hereditary spastic paraplegia (affecting cortical motor neurons), which recapitulate the disease-specific motor neuron and axonal degeneration. We are now building models for spinal cord injury by severing distal axons of cortical neurons. Using these human stem cell-based disease models, my lab will 1) investigate the mechanisms underlying motor neuron and axonal degeneration; 2) build high-throughput and high-content drug-screening systems; 3) identify targets and therapeutic agents to rescue motor neuron and axonal degeneration and to promote axonal regeneration. Our long-term goals are to understand the pathogenic mechanisms and to develop therapies for the treatment of theses debilitating diseases.