The University of Texas Medical School at Houston
Department of Microbiology and Molecular Genetics

Danielle Garsin, Ph.D.

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  • Danielle Garsin, Ph.D.Associate Professor
  • Department of Microbiology &
    Molecular Genetics
  • University of Texas-Houston Medical School
    6431 Fannin Street, MSB 1.168
    Houston, Texas 77030
  • Telephone: (713) 500-5454
    Laboratory Telephone: (713) 500-6579
    e-mail:danielle.a.garsin@uth.tmc.edu

 

Education:

Ph.D., Harvard University, 1999

Postdoctoral Fellow, Massachusetts General Hospital / Harvard Medical School

Research Interests:

Elucidation of innate immune responses using C. elegans as a model host.
Mechanisms of gene regulation in the human pathogen Enterococcus faecalis.

The emergence of untreatable bacterial infection in modern medicine is due to several factors. The hospital patient population is increasingly elderly and immune-compromised, creating a pool of susceptible hosts. The overuse of antibiotics has provided the necessary selective pressure for the development of resistance. Pathogenic bacteria have seemingly endless versatility in creating and sharing mechanisms of resistance. As the development of antibiotic resistance continues to erode one of the greatest advances in modern health care, it is crucial to identify alternative strategies that can form the basis of novel anti-infective therapies. One approach is to target the immune response to more effectively dispel infection.

To this end, one focus of my laboratory’s research includes studies of the host response to pathogens using a tiny worm called C. elegans as a model host. C. elegans has favorable characteristics that include a short 3-day lifecycle during which hundreds of progeny are produced, small size and ease of laboratory cultivation, a fully sequenced genome and a vast array of molecular and genetic tools and resources. Interestingly, C. elegans become sick and die when fed on many human pathogens, making this approach possible. Importantly, many of the same immune defense signaling pathways and mechanisms employed by higher animals appear to also be at play in the worm. For example, my laboratory discovered that C. elegans produces reactive oxygen species (ROS) in response to pathogens, a defense mechanism analogous to the oxidative burst that occurs in human phagocytic cells. We are in the process of identifying the machinery and the regulators that generate this response, characterizing its role in C. elegans immunity, and ultimately applying our knowledge to better understand this response in humans.

Our studies of host immune response to human bacterial infection are particularly focused on Enterococcus faecalis now the second or third most common hospital-acquired infection, but amenable to laboratory studies due to the existence of complete array of molecular tools. In a screen for mutants attenuated in killing C. elegans we discovered that mutations in an operon encoding for ethanolamine utilization affected virulence. Although possible connections between ethanolamine utilization and bacterial pathogenesis are documented in the literature (Garsin 2010), we have focused our initial studies on dissecting the regulation of this operon, as it contains several novel features associated with post-transcriptional regulation. These include an AdoCbl-binding riboswitch and a series of transcription terminators regulated by an RNA-binding two-component system. With the growing realization of the importance of regulatory RNAs to the control of biological systems, we are well poised to make significant discoveries investigating this system.

Selected Publications:

  • Cruz, M.R., C.E. Graham, B.C. Gagliano, M.C. Lorenz, D. A. Garsin (2013). Enterococcus faecalis inhibits hyphal morphogenesis and virulence of Candida albicans. Infect Immun. 81:189-200. PMCID: PMC3536143. [abstract]
  • van der Hoeven, R., K.C. McCallum, D. A. Garsin (2012). Speculations on the activation of ROS generation in C. elegans innate immune signaling. WORM 1:160-163 [abstract]
  • DebRoy, S., R. van der Hoeven, K.V. Singh, P. Gao, B.R. Harvey, B.E. Murray, D. A. Garsin (2012). Development of a genomic site for gene integration and expression in Enterococcus faecalis. J Microbiol Methods. 90:1-8. PMCID: PMC3358487. [abstract]
  • Ramesh, A., S. DebRoy, J.R. Goodson, K.A. Fox, H. Faz, D. A. *Garsin, W.C. *Winkler. (2012). The mechanism for RNA recognition by ANTAR regulators of gene expression. PLoS Genet. 8, e1002666. PMCID: PMC3369931 [abstract]. *D.A. Garsin and W.C. Winkler are co-corresponding authors, accompanied by a commentary.
  • van der Hoeven, R., K.C. McCallum, M.R. Cruz, D. A. Garsin (2011). Reactive oxygen species generated by Ce-Duox1/BLI-3 in response to infection activates the oxidative stress transcription factor SKN-1 in C. elegans via MAPK signaling. PLoS Pathog. 7, e1002453. PMCID: 3245310.[abstract]
  • Garsin, D. A., R. J. L. Willems (2010). Insights into the Biofilm Lifestyle of Enterococci. Virulence. 1, 219-221. [abstract]
  • Garsin, D. A. (2010). Ethanolamine Utilization in Bacterial Pathogens: Roles and Regulation. Nat Rev Microbiol. 8, 290-295. PMCID: 2950637. [abstract]
  • Chavez, V., A. Mohri-Shiomi, D. A. Garsin (2009). Ce-Duox1/BLI-3 Generates Reactive Oxygen Species (ROS) as a Protective Innate Immune Mechanism in Caenorhabditis elegans. Infect Immun. 77, 4983-4989. PMCID: 2772517.[abstract]
  • Creti R., F. Fabretti, S. Koch, J. Huebner, D. A. Garsin, L. Baldassarri, L Montanaro., C. R. Arciola (2009). Surface Protein EF3314 Contributes to Virulence Properties of Enterococcus faecalis. Int J Artif Organs. 32, 611-620. [abstract]
  • Abranches, J, AR Martinez, JK Kajfasz, V Chavez, DA Garsin, JA Lemos (2009). The Molecular Alarmone (p)ppGpp Mediates Stress Responses, Vancomycin Tolerance and Virulence in Enterococcus faecalis. J Bacteriol. 191, 2248-2256. [abstract]
  • Fox, KA, A Ramesh, JE Stearns, A Bourgogne, A Reyes-Jara, WC Winkler, DA Garsin (2009). Multiple Posttranscriptional Regulatory Mechanisms Partner to Control Ethanolamine Utilization in Enterococcus faecalis. Proc Natl Acad Sci U S A. 106, 4435-4440. [abstract]
  • Bourgogne A, DA Garsin, X Qin, KV Singh, J Sillanpaa, S Yerrapragada, Y Ding, S Dugan-Rocha, C Buhay, H Shen, G Chen, G Williams, D Muzny, A Maadani, KA Fox, J Gioia, L Chen, Y Shang, CA Arias, SR Nallapareddy, M Zhao, VP Prakash, S Chowdhury, H Jiang, RA Gibbs, BE Murray, SK Highlander and GM Weinstock (2008).Large Scale Variation in Enterococcus faecalis Illustrated by the Genome Analysis of Strain OG1RF. Genome Biol. 9:R110 [abstract]
  • Mohri-Shiomi, A., DA Garsin (2008). Insulin Signaling and the Heat Shock Response Modulate Protein Homeostasis in the Caenorhabditis elegans Intestine during Infection. Journal of Biological Chemistry 283:194-201 [abstract]
  • Bourgogne A, KV Singh, KA Fox, KJ Plughoeft, BE Murray, DA Garsin (2007). EbpR is Important for Biofilm Formation by Activating Expression of the Endocarditis and Biofilm-Associated Pilus Operon (ebpABC) of Enterococcus faecalis OG1RF. Journal of Bacteriology. 189:6490-6493 [abstract]
  • Chavez V, A Mohri-Shiomi, A Maadani, LA Vega, DA Garsin (2007). Oxidative Stress Enzymes are Required for DAF-16 Mediated Immunity due to Generation of Reactive Oxygen Species by C. elegans. Genetics 176:1567-1577. [abstract]
  • Maadani A, KA Fox, E Mylonakis, DA Garsin (2007). Enterococcus faecalis Mutations Affecting virulence in the C. elegans Model Host. Infection and Immunity. 75, 2634-2637. [abstract]
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