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.Assistant 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:

C. elegans as a model host for understanding the genetics of bacterial infection

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 bacterial targets and immune pathways that can form the basis of novel anti-infective therapies.

To this end, the research in my laboratory is directed at understanding the genetics of bacterial infection from both the pathogen and host's perspectives. Specifically we have developed C. elegans as a model host for elucidating mechanisms of Enterococcus faecalis pathogenesis, now the second or third most common hospital-acquired agent of infection, but amenable to laboratory studies due to the existence of molecular tools such as shuttle vectors, transposons and an inducible expression system. 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.

It has been observed that C. elegans become sick and die when fed on various bacterial pathogens. Importantly, these pathogens appear to use many of the same virulence mechanisms to cause disease in nematodes as they use in mammalian hosts, and nematodes share many of the same defense signaling pathways with higher animals. The use of a nematode as an alternative host has two distinct advantages compared to conventional animal models. First, thousands of pathogen mutants can be individually screened for attenuation in C. elegans, a process that would be unethical and prohibitively expensive in a mammalian animal model system. Second, host response to pathogen attack can be studied in conjunction with selected worm mutants that display altered responses to bacterial infection.

Projects in my laboratory include characterization of newly identified E. faecalis virulence factors found by screening for attenuation in C. elegans, and observed to be less virulent in the mouse. We are also following up on previous studies that implicated the insulin signaling pathway in C. elegans' resistance, our goal being to understand the mechanism by which this pathway contributes. Additionally we have discovered that the worm produces reactive oxygen species (ROS) in response to pathogens, a possible 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 and characterizing its role in C. elegans immunity.

Selected Publications:

  • 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]
  • Nallapareddy SR, KV Singh, J Sillanpaa, DA Garsin, M Hook, BE Murray (2006). Endocarditis and biofilm-associated pili of Enterococcus faecalis. The Journal of Clinical Investigation. 116, 2799-2807. [abstract]
  • Garsin, D. A.: Microbiology. Peptide signals sense and destroy target cells (2004). Science. 306, 2202-2203. [abstract]
  • Garsin, D. A., J. Urbach, J. C. Huguet-Tapia, J. E. Peters, F. M. Ausubel (2004). Construction of an Enterococcus faecalis Tn917-mediated gene disruption library offers insight into Tn917 insertion patterns. Journal of Bacteriology 186, 7280-7289. [abstract]
  • Garsin DA, JM Villaneuva, J Begun, DH Kim, CD Sifri, SB Calderwood and FM Ausubel (2003). Long-lived C. elegans daf-2 mutants are Resistant to Bacterial Pathogens. Science. 300, 1921. [abstract]
  • Sifri CD, E Mylonakis, KV Singh, X Qin, DA Garsin, BE Murray, FM Ausubel, SB Calderwood (2002). Virulence Effect of Enterococcus faecalis Protease Genes and the Quorum-Sensing Locus fsr in Caenorhabditis elegans and Mice. Infection and Immunity. 70, 5647-5650. [abstract]
  • Kim DA*, R Feinbaum*, G Alloing, FE Emerson, DA Garsin, H Inoue, M Tanaka-Hino, N Hisamoto, K Matsumoto, M Tan, FM Ausubel (2002). A conserved p38 MAP Kinase Pathway in Caenorhabditis elegans innate Immunity. Science. 297, 623-626. [abstract]
  • Garsin DA, CD Sifri, E Mylonakis, X Qin, KV Singh, BE Murray, SB Calderwood and FM Ausubel (2001). A simple model host for identifying Gram-positive virulence factors. Proc. Natl. Acad. Sci. 98, 10892-10897. [abstract]
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