Description of Research Expertise:
Genomic and metagenomic approaches to understand cutaneous host-microbe interactions 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.
Zheng Qi, Grice Elizabeth A: AlignerBoost: A Generalized Software Toolkit for Boosting Next-Gen Sequencing Mapping Accuracy Using a Bayesian-Based Mapping Quality Framework. PLoS computational biology 12 (10): e1005096,2016.
Kalan Lindsay, Loesche Michael, Hodkinson Brendan P, Heilmann Kristopher, Ruthel Gordon, Gardner Sue E, Grice Elizabeth A: Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing. mBio 7 (5): e01058-16,2016.
Loesche Michael, Gardner Sue E, Kalan Lindsay, Horwinski Joseph, Zheng Qi, Hodkinson Brendan P, Tyldsley Amanda S, Franciscus Carrie L, Hillis Stephen L, Mehta Samir, Margolis David J, Grice Elizabeth A: Temporal stability in chronic wound microbiota is associated with poor healing. The Journal of Investigative Dermatology 137 (1): 237-244,2016.
Ibiza Sales, García-Cassani Bethania, Ribeiro Hélder, Carvalho Tânia, Almeida Luís, Marques Rute, Misic Ana M, Bartow-McKenney Casey, Larson Denise M, Pavan William J, Eberl Gérard, Grice Elizabeth A, Veiga-Fernandes Henrique: Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature 535 (7612): 440-3,2016.
Bradley Charles W, Morris Daniel O, Rankin Shelley C, Cain Christine L, Misic Ana M, Houser Timothy, Mauldin Elizabeth A, Grice Elizabeth A: Longitudinal Evaluation of the Skin Microbiome and Association with Microenvironment and Treatment in Canine Atopic Dermatitis. The Journal of Investigative Dermatology 136 (6): 1182-90,2016.
Meisel Jacquelyn S, Hannigan Geoffrey D, Tyldsley Amanda S, SanMiguel Adam J, Hodkinson Brendan P, Zheng Qi, Grice Elizabeth A: Skin microbiome surveys are strongly influenced by experimental design. The Journal of Investigative Dermatology 136 (5): 947-56,2016.
Hannigan Geoffrey D, Meisel Jacquelyn S, Tyldsley Amanda S, Zheng Qi, Hodkinson Brendan P, SanMiguel Adam J, Minot Samuel, Bushman Frederic D, Grice Elizabeth A: The Human Skin Double-Stranded DNA Virome: Topographical and Temporal Diversity, Genetic Enrichment, and Dynamic Associations with the Host Microbiome. mBio 6 (5): e01578-15,2015.
Grice Elizabeth A: The intersection of microbiome and host at the skin interface: genomic- and metagenomic-based insights. Genome Research 25 (10): 1514-20,2015.
Chehoud Christel, Rafail Stavros, Tyldsley Amanda S, Seykora John T, Lambris John D, Grice Elizabeth A: Complement modulates the cutaneous microbiome and inflammatory milieu. Proceedings of the National Academy of Sciences of the United States of America 110 (37): 15061-6,2013.
Gardner Sue E, Hillis Stephen L, Heilmann Kris, Segre Julia A, Grice Elizabeth A: The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Diabetes 62 (3): 923-30,2013.
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