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Denise Garcia

Denise Garcia, PhD

Associate Professor
Department of Biology
Office: PISB 422
adg82@drexel.edu
Phone: 215.571.4534

Additional Sites: The Garcia Lab
Twitter: @TheGarciaLab

Education:

  • PhD, Neurobiology, UCLA, 2005
  • BS, Biology, Specialization in Neuroscience, UC Irvine, 1998

Research Interests:

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.

Selected Publications:

Somaiya R.D., Stebbins K., Gingrich E.C., Xie H., Garcia A.D.R., Campbell J.N., Fox M.A. (2022) Sonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamus eLife

Gingrich E.C., Case K., Garcia A.D.R. (2022) A subpopulation of astrocyte progenitors defined by Sonic hedgehog signaling.  Neural Dev. Jan 14;17(1):2.  PMID: 35027088

Hill S., Fu M., Garcia A.D.R. (2021) Sonic hedgehog signaling in astrocytes. Cell and Molecular Life Sciences. Feb;78(4):1393-1403.  PMID: 33079226

Hill S.*, Blaeser A.*, Coley A.A., Xie Y., Shepard K.A., Harwell C.C., Gao W-J., Garcia A.D.R.  (2019) Sonic hedgehog signaling in astrocytes mediates cell type specific synaptic organization eLife, 8:e45545. PMID: 31194676

Allahyari, R.V., Clark K.L., Shepard K.A., Garcia A.D.R. (2019) Sonic hedgehog signaling is negatively regulated in reactive astrocytes after forebrain stab injury. Sci. Rep. 9(1):565. PMID: 30679745

Garcia A.D.R., Han Y-G., Triplett, J, Farmer W.T., Ihrie R.A., Harwell, C.C. (2018) The elegance of sonic hedgehog: Emerging novel functions for a classic morphogen. J. Neurosci. 38(44):9338-9345. doi: 10.1523/JNEUROSCI.1662-18.2018 PMID: 30381425

Allahyari, R.V., Garcia A.D.R., (2015) Triggering reactive gliosis in vivo by a forebrain stab injury. JoVE, PMID: 26167674

Akins, M.R., Garcia A.D.R., (2015) Adult Neurogenesis. In Bradshaw R. and Stahl (Eds.), Encyclopedia of Cell Biology, Vol. 4 (pp.134 – 140). Waltham, MA, Academic Press.

Petrova R., Garcia A.D.R., Joyner A.L. (2013) Titration of GLI3 repressor activity by sonic hedgehog signaling is critical for maintaining multiple adult neural stem cell and astrocyte functions.  J. Neurosci. 33(44):17490-505. PMID: 24174682

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. PMID: 20943901

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. PMID: 17360577

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. PMID: 17088541

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. PMID: 16291951

Garcia A.D.R., Doan, N.B., Imura, T., Bush, T.G., and Sofroniew, M.V. (2004) GFAP expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat. Neurosci. 7(11):1233-41. PMID: 15494728

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. PMID: 12859339