Denise Garcia, PhD
Office: PISB 422
Lab: PISB 312
Lab Phone: 215.571.4393
Cellular and Molecular Neurobiology
- BS, Biology, Specialization in Neuroscience, UC Irvine, 1998
- PhD, Neurobiology, UCLA, 2005
- Postdoc, Developmental Biology, Memorial Sloan Kettering Cancer Center, 2006 - 2010
- Postdoc, Molecular, Cellular, Developmental Biology, UC Santa Cruz, 2010 – 2013
A fundamental goal in neuroscience is to understand how neural circuits are formed, maintained, and reorganized during development and throughout the life of the organism. Our lab is interested in the cellular interactions that facilitate the establishment of neural circuits, as well as the structural plasticity and reorganization of the CNS in the healthy and injured or diseased states. In particular, we focus on the role of astrocytes, part of the larger family of astroglia in the CNS with diverse morphological and functional properties. Though historically thought to serve primarily as support cells for neurons, astrocytes are now known to play critical roles in a number of neurological processes including the formation, maintenance and plasticity of synaptic connections, and neural repair mechanisms after injury. Moreover, a subset of astroglial cells serve as the predominant neural stem cells in the adult forebrain, generating new neurons throughout life. Our lab is interested in the cellular and molecular mechanisms that define and regulate the diversity of astrocyte function in the intact and injured or diseased CNS. We use mouse genetics to manipulate astrocyte function in vivo, and examine the subsequent effects on both neuronal and astrocyte function. Our lab utilizes conventional and confocal microscopy of fixed tissues, as well as chronic, in vivo imaging by 2 photon laser scanning microscopy to address two primary questions: (1) How do astrocytes contribute to synapse formation and reorganization in vivo? (2) What are the molecular signals that regulate astrocyte function in the intact CNS and following injury? Our research aims to bring novel insight into astrocyte biology, with the ultimate goal of providing a deeper understanding of the cellular and molecular mechanisms regulating neural circuitry.
Garcia A.D.R., Petrova, R., Eng L., Joyner A.L. (2010) Sonic hedgehog regulates discrete populations of astrocytes in the adult mouse forebrain. J. Neurosci., 30(41):13597-608.
Nieman B.J., Shyu J.Y., Rodriguez J.J., Garcia A.D., Joyner A.L., Turnbull D.H. (2010) In vivo MRI of neural cell migration dynamics in the mouse brain. Neuroimage 50(2):456-64.
Gregorian, C., Nakashima, J., Le Belle, J., Ohab, J., Kim, R., Liu, A., Smith, K. B., Groszer, M., Garcia, A.D.R., Sofroniew, M. V., Carmichael, S. T., Kornblum, H. I., Liu, X., Wu, H. (2009) Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogensis. J. Neurosci 29(6):1874-86.
Saxe M.D., Malleret G, Vronskaya S, Mendez I, Garcia A.D.R., Sofroniew MV, Kandel ER, Hen R. (2007) Paradoxical influence of hippocampal neurogenesis on working memory. PNAS 104(11):4642-4646.
Saxe M.D., Battaglia, F., Wang, J.-W., Malleret, G., David, D.J., Monckton, J.E., Garcia A.D.R., Sofroniew, M.V., Kandel, E.R., Santarelli, L., Hen, R., and Drew, M.R. (2006) Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. PNAS 103(46):17501-506.
Dougherty, J., Garcia, A.D.R., Nakano, I., Livingstone, M., Norris, B., Polakiewicz, R., Sofroniew, M.V., Kornblum, H., and Geschwind, D. (2005) PBK/TOPK, a proliferating neural progenitor-specific mitogen-activated protein kinase kinase. J. Neurosci. 25(46):10773-85.
Garcia, A.D.R., Doan, N.B., Imura, T., Bush, T.G., and Sofroniew, M.V. (2004) GFAP expressing progenitors are the principle source of constitutive neurogenesis in adult mouse forebrain. Nat. Neurosci. 7(11):1233-41.
Morshead, C.M., Garcia, A.D.R., Sofroniew, M.V. and Van Der Kooy, D. (2003) The ablation of glial fibrillary acidic protein-positive cells from the adult central nervous system results in the loss of forebrain neural stem cells but not retinal stem cells. Eur. J. Neurosci. 18:76-84.
Rodriguez, J.J., Garcia, D.R., Nakabeppu, Y., Pickel, V.M. (2001) Enhancement of laminar FosB expression in frontal cortex of rats receiving long chronic clozapine administration. Experimental Neurology 168(2):392-401.
Rodriguez, J.J., Garcia, D.R., Nakabeppu, Y., Pickel, V.M. (2001) FosB in rat striatum: Normal regional distribution and enhanced expression after 6-month haloperidol administration. Synapse 39:122-132.
Rodriguez, J.J., Garcia, D.R., Nakabeppu, Y., Pickel, V.M. (1999) Subcellular distribution of 5-hydroxytryptamine 2a and N-methyl-D-aspartate receptors within single neurons in rat motor and limbic striatum. Journal of Comparative Neurology 413(2):219-31.