Penn Dermatology Faculty and Investigators

Description of Research Expertise

Research Interests:
Genomic approaches to understand host-microbe interactions at the cutaneous surface in health and disease.

Keywords:
host-microbe interactions, metagenomic analysis of microbial communities, diabetic ulcers, wound healing, chronic wounds, inflammatory skin disease, innate immunity and cutaneous defense

Research Description:
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.

In particular, our lab is interested in non-healing skin wounds, such as those that result from neuropathy and/or vasculopathy associated with diabetes and/or advanced age. Chronic inflammation and microbial colonization and infection are frequently observed in non-healing wounds. Little is understood about the specific role of microbes and how they and their products influence the host skin innate immune response during wound healing. We are genetically dissecting the role of these two intertwined components of impaired wound healing, the microbiota and the host cutaneous immune response; in what we hypothesize is a self-amplifying cycle of microbial colonization, inflammation, and tissue destruction.

In this 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.


Rotation Projects:
A wide range of projects are available in the lab for rotation students. Projects can be tailored to the specific interests of the student, and can consist of work that is wet lab (i.e. molecular biology, genetics, microbiology) or dry lab (i.e. bioinformatics, computational biology) or a combination of both. Please contact Dr. Grice to discuss in further detail.

Lab Personnel:
Amanda Tyldsley, Research Specialist
Geoffrey Hannigan, CAMB dissertation student (GTV)
Ana Misic, Ph.D., Post-doctoral fellow
Brendan Hodkinson, Ph.D., Post-doctoral fellow
Christel Chehoud, GCB rotation student
Adam Sanmiguel, CAMB rotation student (MVP)