Jinhui Chen, M.D., Ph.D.
Institute of Biochemistry, Chinese Academy of Sciences (1997). Postdoctoral training at Washington University in St. Louis and Harvard Medical school.
The long-term goals of my laboratory are to explore the molecular and cellular biology of stem cells and to seek the potential of stem cells for repairing neocortical circuitry damaged by neurodegenerative diseases or injuries.
Molecular and Cellular Biology of Stem Cells
Stem cell research offers unprecedented opportunities to explore fundamental questions of biology and to develop novel medical therapies for debilitating diseases such as neurodegenerative diseases. Despite significant progress in our understanding that stem cells have the ability to self-renew and differentiate into many cell types, little is known about the molecular and cellular mechanisms that control the behavior of stem cells. We have been able to culture neural stem cells and manipulate the gene expressions both in vitro and in vivo, which provide ideal systems to analyze the pathways that control fate choices. The main focus of research in my laboratory will be the cellular and molecular mechanisms that regulate the proliferation, differentiation and survival of neural stem cells and their progeny in the brain during both development and adulthood. Our studies will seek to discover and describe molecules that control cell-fate decision, both in vitro and in vivo. These molecules may be used to expand the neural stem cells in vitro and induce the neural stem cells to differentiate into specific neural cell types, which will be crucial in the development of cell-based therapies and tissue engineering for neurodegenerative diseases or nervous system injuries.
Induced Neuroregeneration in the Mammalian Brain
A better understanding of stem cell biology may lead to the improvement of the therapeutic potential of stem cells. We have successfully induced neuroregeneration of pyramidal neurons from stem cells or from more restricted precursors in the adult mouse brain. We will further investigate how neural stem cells differentiate into mature neurons, migrate to appropriate sites, form synapses with their targets and integrate into the existing circuitry. Our studies will develop therapeutic strategies for treating neurological disorders where pathogenesis is thought to involve the loss of neurons or supporting cells, including Parkinson's Disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS).
Current Techniques Involved
A broad range of molecular, cellular and animal model techniques have been actively combined in our current research including gene cloning, PCR, neural stem cell culture, viral gene expression systems, Microarrays, conditional gene knockout, target induced cell death, animal surgery, immunohistochemistry, and proteomics.
Huashun Li*, Jinhui Chen*, Wei wu*, Tanya Fagaly, Lijuan Zhou, Wenlin Yuan, Sophie Dupuis, Zhihong Jiang, William Nash, Carrie Gick, David M. Ornitz, Jane Y. Wu, Yi Rao. (1999) Vertebrate Slit, a Secreted Ligand for the Transmembrance Protein Roundabout, is a Repellent for Olfactory Bulb Axons. Cell, 96: 807-818 *(co-first author). Review on this topic: Cell. 1999 Apr 2;97(1):1-4. Nature. 1999 Apr 8;398(6727):462-3. Neuron. 1999 Apr;22(4):649-52. Curr. Biol. 1999 Jun 17;9(12):R432-5.
Wei Wu, Kit Wong, Jinhui Chen, Zhihong Jiang, Jane Y. Wu, Yi Rao. (1999) Directional Guidance of Neuronal Migration in the Olfactory System by the Secreted Protein Slit. Nature (Article), 400: 331-336. Comment on: Nature. 1999 Jul 22; 400 (6742):315-6.
Wenlin Yuan, Lijuan Zhou, Jinhui Chen, Jane Y. Wu, David M. Ornitz. (1999) The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance. Developmental Biology, 212:290-306.
Jinhui Chen, Wei Wu, Huashun Li, Tanya Fagaly, Lijuan Zhou, Jane Y. Wu, Yi Rao. (2000) Embryonic expression, extracellular secretion, and chemorepulsive activity of Xenopus Slit. Neuroscience, 96: 231-236.
Jinhui Chen, Leng Wen, Sophie Dupuis, Jane Y. Wu, Yi Rao. (2001) The N- terminal Leucine-Rich Regions in Slit Are Sufficient to Repel Olfactory Bulb Axons and Subventricular Zone Neurons. J of Neuroscience, 21(5): 1548-1556.
Fortunel NO, Otu HH, Ng HH, Chen J, Mu X, Chevassut T, Li X, Joseph M, Bailey C, Hatzfeld JA, Hatzfeld A, Usta F, Vega VB, Long PM, Libermann TA, Lim B. Comment on " 'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature". Science. 2003 Oct 17;302(5644):393.
Jinhui Chen, Sanjay S. Magavi, Jeffrey D. Macklis. (2004) Neurogenesis of corticospinal motor neurons extending process to spinal cord in adult mice. PNAS, 101(46): 16357-16362
Paola Arlotta, Bradley J. Molyneaux, Jinhui Chen, Inoue J, Kominami R, Jeffrey D. Macklis. (2005) Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development In Vivo. Neuron. 20, 45(2): 207-211.
University of Kentucky
Tel: (859) 323-5688