Genomic approaches to understand host-microbe interactions at the cutaneous surface in health and disease.
host-microbe interactions, metagenomic analysis of microbial communities, diabetic ulcers, wound healing, chronic wounds, inflammatory skin disease, innate immunity and cutaneous defense
The skin is a formidable barrier and the first line of defense against the external environment. The skin is also host to myriad microbes (the "microbiome") including diverse communities of bacteria, fungi, viruses, and even arthropods. Our research uses an interdisciplinary approach to understand how these microbial communities coexist and interact with the host at the skin surface, in health and disease. Generally, homeostasis is maintained at the skin surface despite colonization by microbes. However, we hypothesize that disruptions in the dynamic interplay between the skin barrier, the microbiome, and the cutaneous defense response may in part be responsible for a variety of inflammatory skin disorders.
One particular area of interest in the lab is non-healing wounds, including diabetic foot ulcers and acute traumatic wounds. In one aspect of our work, we have partnered with clinicans to undertake clinical studies to delineate microbiome dynamics during wound healing and infection. In another aspect, we are genetically dissecting the role of the microbiota and the host cutaneous immune response in mouse models of impaired wound healing.
In these and other projects in the lab we employ deep sequencing of microbe-specific marker genes (i.e. the prokaryote-specific 16S ribosomal RNA gene) and bulk sequencing of microbial DNA ("metagenomics") to examine microbial community dynamics and responses to perturbation, both from a taxonomical and a functional standpoint. These approaches circumvent traditional culture-based approaches that are biased towards those microbes that grow readily under standard laboratory culture conditions.
The long-term goal of our research is to leverage our understanding of microbiome-host interactions to diagnose and treat skin disorders. The need for novel therapeutics is increasingly evident as multi-drug resistant bacterial strains continue to evade our antibiotic resources. The skin microbiome is an information-rich, readily accessible and modifiable factor. Towards fulfilling the enormous therapeutic and diagnostic potential of the skin microbiome, we are addressing fundamental, clinically relevant questions regarding host-microbe interactions at the skin surface.
Amanda Tyldsley, Research Specialist
Geoffrey Hannigan, CAMB dissertation student (GTV)
Ana Misic, Ph.D., Post-doctoral fellow
Brendan Hodkinson, Ph.D., Post-doctoral fellow
Jacquelyn Meisel, GCB dissertation student
Adam Sanmiguel, CAMB dissertation student (MVP)
Kong Heidi H, Oh Julia, Deming Clay, Conlan Sean, Grice Elizabeth A, Beatson Melony, Nomicos Effie, Polley Eric, Komarow Hirsh D, Program Nisc Comparative Sequence, Murray Patrick R, Turner Maria L, Segre Julia A: Temporal shifts in the skin microbiome associated with atopic dermatitis disease flares and treatment. Genome research 22(5): 850-9, Feb 2012.
Grice Elizabeth A, Segre Julia A: Interaction of the microbiome with the innate immune response in chronic wounds. Advances in Experimental Medicine and Biology 946: 55-68, 2012.
Grice Elizabeth A, Segre Julia A: The skin microbiome. Nature reviews. Microbiology 9(4): 244-53, Apr 2011.
Grice Elizabeth A, Snitkin Evan S, Yockey Laura J, Bermudez Dustin M, , Liechty Kenneth W, Segre Julia A: Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response. Proceedings of the National Academy of Sciences of the United States of America 107(33): 14799-804, Aug 2010.
Scharschmidt Tiffany C, List Karin, Grice Elizabeth A, Szabo Roman, , Renaud Gabriel, Lee Chyi-Chia R, Wolfsberg Tyra G, Bugge Thomas H, Segre Julia A: Matriptase-deficient mice exhibit ichthyotic skin with a selective shift in skin microbiota. The Journal of Investigative Dermatology 129(10): 2435-42, Oct 2009.
Grice Elizabeth A, Kong Heidi H, Conlan Sean, Deming Clayton B, Davis Joie, Young Alice C, , Bouffard Gerard G, Blakesley Robert W, Murray Patrick R, Green Eric D, Turner Maria L, Segre Julia A: Topographical and temporal diversity of the human skin microbiome. Science 324(5931): 1190-2, May 2009.
Grice Elizabeth A, Kong Heidi H, Renaud Gabriel, Young Alice C, , Bouffard Gerard G, Blakesley Robert W, Wolfsberg Tyra G, Turner Maria L, Segre Julia A: A diversity profile of the human skin microbiota. Genome research 18(7): 1043-50, Jul 2008.
Fisher Shannon*, Grice Elizabeth A*, Vinton Ryan M, Bessling Seneca L, McCallion Andrew S: Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science 312(5771): 276-9, Apr 2006 Notes: *Equal contributions.
Fisher Shannon*, Grice Elizabeth A*, Vinton Ryan M, Bessling Seneca L, Urasaki Akihiro, Kawakami Koichi, McCallion Andrew S: Evaluating the biological relevance of putative enhancers using Tol2 transposon-mediated transgenesis in zebrafish. Nature Protocols 1(3): 1297-305, 2006 Notes: *Equal contributions.
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Last updated: 09/27/2013
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