Mandy J McGeachy, PhD
Campus: BST South, S719, 3500 Terrace Street
Pittsburgh, PA 15261
- BSc, University of Glasgow, Scotland, UK, 2001
- PhD, University of Edinburgh, Scotland, UK, 2005
- Postdoc, Schering-Plough Biopharma/DNAX, 2009
- Assistant Professor
- Assistant Professor, Division of Rheumatology & Clinical Immunology, Department of Medicine
Th17 cells cause chronic tissue inflammation in autoimmune diseases like psoriasis, multiple sclerosis and Crohn’s disease. However, Th17 cells and other ‘type-17’ cells provide vital protection against commensals and opportunistic pathogens at barrier surfaces, and also aid in wound repair. Many of these effects are achieved through IL-17. Perhaps due to these dual functions of Th17 cells, therapies targeted towards the IL-17 pathway are highly efficacious in some diseases, but have had mixed results in others. The McGeachy lab studies how inflammatory Th17 cells are generated, regulated and mediate their effects through IL-17 in different tissues, with the goal of determining the best approaches to modulate Th17-driven pathology while conserving the beneficial protective roles of Th17 cells.
Key questions being addressed:
1) Molecular mechanisms that regulate Th17 differentiation in humans, with a focus on the interplay between costimulatory and cytokine signaling,
2) Functional regulators of in vivo Th17 effector cell pathogenicity,
3) Regulation of Th17 migration in different tissues,
4) Th17: tissue interactions that lead to stromal cell remodeling during chronic inflammation.
Revu S, Wu J, Henkel M, Rittenhouse N, Menk A, Delgoffe GM, Poholek AC, McGeachy MJ “IL-23 and IL-1b drive human Th17 cell differentiation and metabolic reprogramming in absence of CD28 costimulation” Cell Reports 2018
Hernandez Mir G, McGeachy MJ. “CD73 is expressed by inflammatory Th17 cells in experimental autoimmune encephalomyelitis but does not limit differentiation or pathogenesis” Plos One 2017
Singh D, Henkel M, Sendon BB, Feng J, Fabio A, Metes D, Moreland LW, McGeachy MJ. “Analysis of CXCR5+Th17 cells in relation to disease activity and TNF inhibitor therapy in Rheumatoid Arthritis”. Scientific Reports 2016
Du F, Garg AV, Kosar K, Majumder S, Kugler DG, Mir GH, Maggio M, Henkel M, Lacy-Hulbert A, McGeachy MJ “Inflammatory Th17 Cells Express Integrin αvβ3 for Pathogenic Function” Cell Reports, 2016
Haines CJ, Chen Y, Blumenschein WB, Jain R, Chang C, Joyce-Shaikh B, Porth K, Leech MD, Boniface K, Mattson J, Basham B, Anderton SM, McClanahan T, Sadekova S, Cua DJ, McGeachy MJ “Autoimmune Th17 Memory Cell Function and Expansion are Dependent on IL-23” Cell Reports, 2013
Chen Y, Hochweller K, Haines C, Blumenschein WB, McClanahan T, Hammerling G, Cua DJ, McGeachy MJ. Foxp3+ Regulatory T cells Promote Th17 Development in vivo. Immunity 2011.