Dr. Artlett is interested in fibrosis and in the signaling pathways that drive the expression of collagen. This interest includes several areas of expertise including inflammasome signaling, the export of procollagen from the endoplasmic reticulum and the development of therapeutics for the treatment of fibrotic disorders.

Research staff: Lianne Connolly

We are interested in what mediates the scleroderma (SSc) phenotype by understanding what regulates fibrosis in the skin and internal tissues in these patients. SSc is a fibrotic disease of unknown origin that is predominantly found in women. What is apparent is the uncontrolled fibrosis in the dermis and internal organs that affects morbidity and leads to mortality in these patients. Understanding the mechanisms whereby myofibroblasts and fibroblasts interact with the extracellular matrix (ECM) is crucial to the understanding of fibrosis in SSc. It also has applications in wound healing as well. Fibroblasts are sensitive to signals from the ECM, and interaction of fibroblasts with the ECM is essential in many physiological and pathological processes.

In SSc, the inflammasome is integrally involved in fibrosis, and we observed a significant reduction in collagen deposition when the inflammasome was inactivated. We have also identified the crucial role for miR-155 and IL-1 in driving this fibrotic response. More recently we have become interested in the export of procollagen from the endoplasmic reticulum and the factors that regulate this during fibrosis. We have identified several crucial proteins that are required for the procollagen export that are highly upregulated. In addition, we have identified that caspase-1, and the IL-1 and TGFβ receptors are involved.

Given our expertise in fibrosis, we also work with several small biotech companies to meet their experimental needs. One project is to investigate a small novel peptide 18 amino acids in length, acALY18. The anti-fibrotic nature of acALY18 is currently under investigation.

Selected publications
(See all Carol Artlett's publications in PubMed.)

"Inflammasomes in wound healing and fibrosis"
Artlett CM
Journal of Pathology; 229(2):157-67, January 2013

"Recent Advances in Scleroderma Pulmonary Fibrosis"
Artlett CM
Advances in Medicine and Biology. Editor LA Burnhardt. Vol 53, Chapter 3, 2012.

"The law of unintended consequences and antibiotics"
Thacker JD and CM Artlett
Open Journal of Immunology, 2: 59-64, 2012.

"The role of the NLRP3 inflammasome in fibrosis"
Artlett CM
The Open Rheumatology Journal, 6 (Suppl 1, M3): 80-86, 2012.

"NLRP3 Inflammasome is a Target for Development of Broad-Spectrum Anti-Infective Drugs"
Thacker JD, Sassi-Gaha S, Stephens C, Purohit M, Rest RF, and CM Artlett
Antimicrobial Agents and Chemotherapeutics, 56: 1921-1930, 2012.

"The Inflammasome Activating Caspase-1 Mediates Fibrosis and Myofibroblast Differentiation in Systemic Sclerosis"
Artlett CM, Sassi-Gaha S, Rieger JL, Boesteanu AC, Feghali-Bostwick CA, and PD. Katsikis
Arthritis and Rheumatism, 63: 3563-3574, 2011.

Modification of collagen by 3-deoxyglucosone alters wound healing through differential regulation of p38 MAP kinase.
Loughlin DT, and Artlett CM.
PLOS One, 6:e18676, 2011.

Animal models of scleroderma: Fresh Insights.
Artlett CM.
Current Opinion in Rheumatology, 22:677-82, 2010.

Precursor of Advanced Glycation End Products 3-deoxyglucosone Mediates ER-stress-induced Caspase-3 Activation of Human Dermal Fibroblasts through NAD(P)H Oxidase 4.
Loughlin DT, and Artlett CM.
PLOS One, 5: e11093, 2010.

Two dicarbonyl compounds, 3-deoxyglucosone and methylglyoxal, differentially modulate dermal fibroblasts.
Sassi-Gaha S, Loughlin DT, Kappler F, Schwartz ML, Su Bangying, Tobia AM, and Artlett CM.
Matrix Biology, 29: 127-134, 2010.

1-peptidyl-2,3-diacryglyceride: an endogenous lipopeptide is an activator of the innate arm of the immune response.
Thacker JD, Purohit M, Sassi-Gaha S, Rest RF, and Artlett CM.
Journal of Natural Products 72: 1993-1999, 2009.

3-Deoxyglucosone-Collagen Alters Human Dermal Fibroblast Migration and Adhesion: Implications for Impaired Wound Healing in Patients with Diabetes. Wound Repair Regen.
Loughlin DT, and Artlett CM.
17: 739-749, 2009.

Receptor for advanced glycation end products and neuronal deficit in the fatal brain edema of diabetic ketoacidosis.
Hoffman WH, Artlett CM, Zhang W, Kriepke CW, Passmore GG, Rafols JA, and Sima AA. 
Brain Research, 1238: 154-162, 2008.

IL-15 treatment during acute SIV infection increases viral set point and accelerates disease progression.
Mueller YM, Duc HD, Altork SR, Artlett CM, Graceley EJ, Katsetos CD, Legido A, Villinger F, Altman JD, Brown CR, Lewis MG, and Katsikis PD.
The Journal of Immunology, 180: 350-360, 2008.

Allograft inflammatory factor-1 and tumor necrosis factor single nucleotide polymorphism in systemic sclerosis.
Otieno FG, Lopez AM, Jimenez SA, Gentiletti J, and Artlett CM.
Tissue Antigens, 69: 583-591, 2007.