Dr Joanne Konkel

Joanne Konkel – Research summary

Dr Joanne Konkel

Dr Joanne Konkel

Mucosal barrier sites pose a particular challenge for the immune system. These barriers, such as the Gastrointestinal (GI) tract and Oral mucosa, are sites of frequent pathogen invasion but also home to diverse commensal microbial communities. As such, the immune system must be carefully tailored to the tissue microenvironment to limit aberrant responses to commensals while allowing for rapid development of an immune response to protect against the invader. Failure to achieve this threatens the integrity of mucosal barriers and can lead to severe pathological consequences, such as the development of inflammatory bowel diseases (IBD) (Gastrointestinal tract), and Periodontitis (Oral mucosa). Consequently, specialized immune cell networks have developed to help mediate effective immunological control of these dynamic barrier environments.

Tight control of immune responsiveness is vital at barrier sites. Loss of immune homeostasis at the oral barrier leads to peridontal inflammation resulting in destruction of the tooth supporting tissue and, eventually, underlying bone.

My research programme focuses on understanding how the immune system is tailored to these unique barrier surfaces. Indeed, to mediate immune homeostasis at barrier sites, conventional and unconventional immune cells are present which are locally conditioned by the microenvironment. My recent work has examined the development and differentiation of T cells at barrier sites, understanding how barrier-specific cues, in particular the cytokine TGFβ, educates these cells about their unique environment and drives them to adopt specific phenotypic and functional characteristics.

CD4+ T cells

In establishing my own group I intend to further explore the immune cell networks present at barrier sites, with a particular emphasis on the oral mucosa. These studies are being performed in both human (in collaboration with Dr. N. Moutsopoulos at the NIDCR, NIH, USA) and murine models, parallel studies that allow for a thorough investigation of this often overlooked mucosal site. In brief the research aims are; (1) to mechanistically define the signals that are required to establish the immunological network present at the oral barrier, (2) to understand how the oral immune network mediates immunity and how this contributes to pathological inflammation in the oral cavity, and (3) to understand the influence of immune activity at the oral barrier on immunity at other barrier sites (particularly the Gastrointestinal Tract).

Understanding of the mechanisms behind the immune specialization at barrier sites will not only allow for a better understanding of barrier immunity in human health and disease but could also lead to the identification of targets for the rational development of novel therapeutics.

I am a Fellow in the Institute of Inflammation & Repair.

Email: joanne.konkel@manchester.ac.uk Tel: 0161 275 5133

Publications

Biography

After receiving my BSc in Biochemistry from the University of Bristol, I moved to the University of Edinburgh to undertake a Wellcome Trust funded PhD. Performing these studies in the laboratory of Prof. Stephen Anderton, I became interested in understanding how T cells perceive and respond to their environment and differentiate accordingly. After completing my PhD in 2009 I moved to National Institutes of Health in the USA to undertake my post-doctoral work in the laboratory of Dr. Wanjun Chen in the National Institutes of Dental and Craniofacial Research. It was here that I developed my interest in mucosal immunology and the important mucosal cytokine TGFβ, exploring the development of both conventional T cells and, less well-studied, unconventional T cells residing at barrier sites. These studies led me to begin to start my own group examining the immune cell networks present at barrier sites, with a particular emphasis on the oral mucosa, and how the unique and conventional immune cells present at barrier sites perceive and are locally conditioned by the tissue microenvironment. This has been made possible by a Wellcome Trust funded Stepping-Stones Fellowship at The University of Manchester.

Publications