Danielle A. Garsin, Ph.D.
Dr. Garsin is a professor in the Medical School Department of Microbiology and Molecular Genetics at the University of Texas Health Science Center at Houston. Dr. Garsin came to UTHealth as an assistant professor in 2004 following a postdoctoral fellowship at Massachusetts General Hospital/Harvard Medical School. She earned her Ph.D. in Biochemistry at Harvard University and her B.S. in Biological Sciences at Cornell University.
Dr. Garsin is at heart a bacterial geneticist, and this foundation supports her interests in bacterial pathogenesis, gene regulation, and host-microbe and microbe-microbe interactions. Her studies are centered on the biology of the human bacterial pathogen, Enterococcus faecalis. One NIH-funded research focus is on the post-initiation mechanisms of gene regulation in E. faecalis. Another is on the biology of reactive oxygen species in the immune response elicited in the model host Caenorhabditis elegans. Finally, Dr. Garsin is developing a new project studying the interactions between E. faecalis and the human fungal pathogen, Candida albicans. She and her collaborators discovered that the microbes inhibit each other’s virulence leading to the identification of compounds with potential for anti-infective therapeutic development.
Dr. Garsin has received many commendations for excellence in research and education. In 2004, she received an Ellison Medical Foundation New Scholar Award in Global Infectious Disease and was a finalist in 2008 for Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease. Also in 2008, she was awarded a UT Young Investigator award. She was the recipient of the Dean’s Teaching Excellence Award in 2009 and 2012. Dr. Garsin is currently an associate editor of PLOS Genetics and a permanent member of the Prokaryotic Cell and Molecular Biology (PCMB) NIH review group.
- Postdoctoral Fellow
- Massachusetts General Hospital / Harvard Medical School
- Harvard University, 1999
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-associated infection, but amenable to laboratory studies due to the existence of a 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. We have focused our 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. We are now dissecting how these features work together to turn on and off the expression of the ethanolamine genes as well as studying the spatio-temporal dynamics of the ethanolamine-specific microcompartments that form to carry out the metabolism.
Finally, my lab is engaged in a collaborative project with the Lorenz Laboratory studying the interactions of E. faecalis with the human fungal pathogen Candida albicans. We have recently identified a peptide secreted by E. faecalis that inhibits the pathogenicity and biofilm formation of C. albicans; it showed therapeutic potential in a mouse model. We are starting to examine how C. albicans, likewise, inhibits the virulence and biofilm formation of E. faecalis.
- Graham, C. E., M. R. Cruz, D. A. Garsin*, M. C. Lorenz* (2017). The Enterococcus faecalis Bacteriocin EntV Inhibits Hyphal Morphogenesis, Biofilm Formation, and Virulence of Candida albicans. Proc Natl Acad Sci U S A. doi: 10.1073/pnas.1620432114.
*D. A. Garsin and M. C. Lorenz are co-corresponding authors. https://www.ncbi.nlm.nih.gov/pubmed/28396417
- McCallum K. C., B. Liu, J. C. Fierro-González, P. Swoboda, S. Arur, A. Miranda-Vizuete, D. A. Garsin (2016). TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans. Genetics. 203, 387-402. https://www.ncbi.nlm.nih.gov/pubmed/26920757
- DebRoy, S., M. Gebbie, A. Ramesh, J. R. Goodson, M. R. Cruz, A. van Hoof, W. C. Winkler, D. A. Garsin (2014). A Riboswitch-Containing sRNA Controls Gene Expression by Sequestration of a Response Regulator. Science. 345, 937-940. https://www.ncbi.nlm.nih.gov/pubmed/25146291
- Tiller, G. R., D. A. Garsin (2014). The SKPO-1 Peroxidase Functions in the Hypodermis to Protect C. elegans From Bacterial Infection. Genetics. 197, 515-526. http://www.ncbi.nlm.nih.gov/pubmed/24621828
- 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. http://www.ncbi.nlm.nih.gov/pubmed/23115035