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Duke Medical Center

Chay T. Kuo, MD, PhD
BS, M.I.T.
MD, University of Chicago
PhD, University of Chicago

Assistant Professor,
Dept. of Cell Biology,
Pediatrics, Neurobiology

Chay Kuo

    Neural Stem Cell Biology
Why do we need neural stem cells in the postnatal and adult brain? Are they an integral part of adaptive responses to new stimuli? Do they respond to and participate in disease processes? Or are they contributors to deadly brain tumors? We are interested in the regulation of postnatal neural stem cells and how they modify brain homeostasis in health and disease. Throughout embryonic and postnatal development, neural stem cells give rise to differentiated neurons, astrocytes, and oligodendrocytes which modulate function of the adult nervous system. While during embryogenesis these progenitor cells are relatively abundant and help to construct the overall CNS architecture, during postnatal and adult periods they become restricted to specialized regions in the brain and produce progeny that participate in the modification of neural circuitry and brain homeostasis. The work in my laboratory centers around the molecular pathways regulating these specialized stem cells. A better understanding of these processes may lead to future therapies for patients suffering from pre/postnatal brain injuries, and brain tumors.

Email: chay.kuo@cellbio.duke.edu

330 Nanaline Duke Bldg.
451 Research Dr. Box 3709
Duke Univ. Medical Center Durham, NC 27710

Telephone: (919) 684-4612
Fax: (919) 684-5481
 
    The control of stem cell niche homeostasis
To better understand how stem cells contribute to brain remodeling in health and disease, we focus on the subventricular zone (SVZ) of the lateral ventricles in the postnatal brain, an area (niche) that contains a self-renewing population of neural stem cells. We have developed inducible Cre-transgenic mouse lines, as well as other new tools that can efficiently delete target genes in specific populations of SVZ cells after birth. A major focus in the lab is to elucidate important pathways that regulate stem cell function within the niche architecture - we are particularly interested in how this niche is generated and maintained during the postnatal period, and in pathways controlling stem cell proliferation that can lead to tumor formation. We use a variety of techniques including genetic mouse models, live imaging assays, stem cell cultures, and array analyses to study these processes. We are conducting both in vivo and in vitro-based screens to identify new pathways that regulate SVZ neurogenesis.

    The contribution of neural stem cells and their progeny to brain remodeling
Postnatal-specific disruptions of the SVZ revealed that these neural stem cells have considerable plasticity and can participate in local remodeling and repair – a highly unexpected finding. We are now investigating the molecular mechanisms that regulate this stem cell-mediated repair and remodeling. We are particularly interested in how environmental cues regulate the differentiation of stem cell progeny, and how this process can ultimately transform brain homeostasis in both health (integration into neural circuits) and disease (migration following injury and cancer). Our ability to genetically label and modify SVZ progeny under a variety of conditions, and to then follow their migration and differentiation gives us an unique opportunity to investigate these challenging problems. Our approach includes a combination of mouse genetics, live imaging, in vivo circuit tracing, and collaborations with neural trauma and brain tumor colleagues.

Selected Publications
Kuo, CT, Mirzadeh, Z, Soriano, M, Rasin, M, Wang, D, Shen, J, Sestan, N, Garcia-Verdugo, J, Alvarez-Buylla, A, Jan, LY, and Jan, YN. 2006. Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Cell 127: 1253-64. -PDF-

Kuo, CT, Zhu, SJ, Younger, S, Jan, LY, and Jan, YN. 2006. Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning. Neuron 51: 283-90.

Yu, FW, Kuo, CT, and Jan, YN. 2006. Drosophila neuroblast asymmetric cell division: recent advances and implications for stem cell biology. Neuron 51: 13-20.

Kuo, CT and Jan, YN. 2005. The hand that rocks the spindle. Nature Cell Biol. 7: 858-9.

Kuo, CT, Jan, LY, and Jan, YN. 2005. Dendrite-specific remodeling of Drosophila sensory neurons requires matrix metalloproteases, ubiquitin-proteasome, and ecdysone signaling. PNAS 102: 15230-5.

Buckley, AF, Kuo, CT, and Leiden, JM. 2001. Transcription factor LKLF is sufficient to program T cell quiescence via a c-Myc-dependent pathway. Nature Immunol. 2: 698-704.

Kuo, CT and Leiden, JM. 1999. Transcriptional Regulation of T Lymphocyte Development and Function. Annu. Rev. Immunol. 17: 149-187.

Kuo, CT, Veselits, ML, Barton, KP, Lu, MM, Clendenin, C, and Leiden, JM. 1997. The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Genes & Dev. 11: 2996-3006.

Kuo, CT, Veselits, ML, and Leiden, JM. 1997. LKLF: A transcriptional regulator of single positive T cell quiescence and survival. Science 277: 1986-1990.

Kuo, CT, Morrisey, EE, Anandappa, R, Sigrist, K, Lu, MM, Parmacek, MS, Soudais, C, and Leiden, JM. 1997. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes & Dev. 11: 1048-1060.


Lab personnel
Chay T. Kuo, MD, PhD (principle investigator)
Peer Heine, PhD, Max-Planck Institute for Brain Research (postdoc)
Patricia Paez-Gonzalez, PhD, Universidad de Malaga (postdoc)
Jingjun Li, PhD, UNC Chapel Hill (postdoc)
Anne Buckley, MD, PhD, University of Chicago (research fellow)
Gray Lyons, (MSTP student)
Brooke Buckland, (technician)
Charles Yi, (technician)
Alexander Lazarides, (undergraduate)

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