UK
Department of Anatomy and Neurobiology Faculty
Research
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
Assistant Professor,
Spinal
Cord and BrainInjuryResearchCenter
&
Department of Anatomy and Neurobiology
Research Interests:The
long-term goals of our 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 ourcurrent 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.
Representative
Publications
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 cortico-spinal
motor neurons extending spinal projections in adult mice. Proc. Natl.
Acad. Sci. U. S. A. 101(46):16357-62.
Paola Arlotta, Bradley J.
Molyneaux, Jinhui Chen, Jun Inoue, Ryo Kominami and Jeffrey D.
Macklis. (2005) Neuronal Subtype Specific Genes that Control Corticospinal
Motor Neuron Development in vivo. Neuron, In press
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.
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).