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Duke University


Duke Medical Center

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

George W. Brumley Assistant Professor,
Dept. of Cell Biology,
Pediatrics, Neurobiology

Chay Kuo

    Production and integration of new neurons
Why do we need continued neurogenesis in the postnatal and adult brain? Is it an integral part of adaptive responses to new stimuli? Do stem cells and their progeny respond to and participate in disease processes? And how is this robust generation / integration of new neurons sustained? We are interested in the regulation of postnatal neurogenesis, and how neural stem cells and newborn neurons 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 circuits and homeostasis. The work in my laboratory centers around molecular pathways regulating the generation and integration of new neurons. A better understanding of these processes may lead to future therapies for patients suffering from pre- and postnatal brain injuries.

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Email: chay.kuo@duke.edu
366 Nanaline Duke Bldg.
451 Research Dr. Box 3709
Duke Univ. Medical Center Durham, NC 27710

 Telephone: (919) 684-4612
Fax: (919) 684-5481
 
    Control of SVZ homeostasis and neuronal production
We focus on the subventricular zone (SVZ) along the lateral ventricles in the postnatal brain, an area (niche) that contains a self-renewing population of neural stem cells. Early on, we developed inducible genetic tools to modulate SVZ function in vivo, and have continued to work in this area by merging mouse genetics with optical and electrophysiology tools. Currently, a major focus in the lab is to elucidate important pathways regulating neural stem cell homeostasis within the SVZ architecture - we are particularly interested in how this architecture is generated and maintained during the postnatal period, and in the application of this knowledge to general principles guiding new neuron production. We use a variety of techniques including building novel mouse models, development of new multi-photon imaging platforms, whole-cell recordings, and collaborating with bioengineers to study these processes. We are conducting both in vivo and in vitro-based screens to identify new pathways that regulate SVZ neurogenesis.

    Contribution of stem cells, their progeny, and new neurons to brain remodeling
Postnatal disruptions of the SVZ revealed that resident stem cells and their progeny have considerable plasticity and can participate in local remodeling and repair. We are actively investigating the molecular mechanisms regulating this plasticity. We are particularly interested in how environmental cues may transform the differentiation of newborn neurons, and how this process can ultimately impact brain homeostasis in both health (integration into mature 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 tackle these challenging and exciting problems. Our approach includes a combination of mouse genetics, multi-photon imaging, in vivo circuit tracing, electrophysiology, and collaborations with neural trauma and brain tumor colleagues.

Selected Publications
Paez-Gonzalez, P, Abdi, K., Luciano, D, Liu, Y, Soriano-Navarro, M, Rawlins, E, Bennett, V, Garcia-Verdugo, JM, and Kuo, CT. 2011. Ank3-dependent SVZ niche assembly is required for the continued production of new neurons. Neuron 71: 61-75. (Cover Story) -PDF-

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. (Research Highlights in Nature) -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. (Research Highlights in Nature Rev. Neurosci.)

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. (Accompanied News & Views in Nature Immuol.)

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. (Cover Story)

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

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. (Cover Story)


Lab personnel
Chay T. Kuo, MD, PhD (principle investigator)
Patricia Paez-Gonzalez, PhD, (postdoc)
Khadar Abdi, PhD (postdoc)
Brent Asrican, PhD (postdoc)
Ryan Andersen, PhD (postdoc)
Gray Lyons, (grad student, MSTP)
Nick Luciano, (grad student, Neurobiology)
Erica Rodriguez, (grad student, Neurobiology)
Dawn Fromme (technician)
Samantha Collins (technician)

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