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My research is primarily focused on fibrosis and the signaling pathways that not only drive the expression of collagen but promote procollagen export from the endoplasmic reticulum. This interest includes several areas of expertise involving inflammasome signaling, and the role of miR-155 and IL-1 in promoting fibrosis. More recent work has focused on the endoplasmic reticulum and the role of TANGO1 in procollagen export. TANGO1 accompanied by cTAGE5 is needed for the expansion of tubules for protein export to the Golgi apparatus. Without these two proteins, collagen and indeed a milieu of other high molecular weight extracellular proteins cannot be exported and then secreted from the cell. Our research is focused on pathways that intersect with the inflammasome that induce TANGO1 and cTAGE5 expression and thereby promote fibrosis. Understanding these mechanisms is crucial to developing effective therapeutics that will control this pathology. During our research, we have identified a small molecule that is anti-fibrotic because it targets TANGO1 expression. We believe this could be an effective therapeutic for the fibrotic autoimmune disease systemic sclerosis (scleroderma). In these patients where there is uncontrolled systemic fibrosis that severely affects their quality of life leading to an early death post-diagnosis.

Our laboratory is also focused on the development of therapeutics that can advance the healing of chronic wounds. The process of normal wound repair undergoes well-defined time frames for healing, correlating with an initial inflammatory phase, a proliferative phase, and finally a remodeling phase. This process requires the recruitment of inflammatory cells into the wound but also the differentiation and proliferation of fibroblasts into myofibroblasts inducing wound closure. Myofibroblasts are the most critical cell type in wound healing mediating the expression of elevated levels of collagen and contraction of wound margins. However, chronic wounds have stalled in healing with reduced ECM expression, reduced myofibroblast numbers, and increased degradation of the ECM by metalloproteinases. We have found an FDA-approved compound promotes critical features of wound healing including increased collagen synthesis, increased expression of growth factors, and increased fibroblast proliferation and migration. The goal of this project is to develop this compound as a novel inexpensive molecule that can be added to hydrogels for release over time to enhance wound healing.

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 TGF尾 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

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Artlett CM, Connolly LM
Fibrosis. 2023, 1(2), 10008 (December 2023)

Connolly LM, McMahon IG, McFalls CM, Bhat AM, Artlett CM
Arthritis and Rheumatology 75:1831-1841, 2023

Artlett CM
Biomolecules, 12: 634, 2022

Hoffman WH, Ishikawa T, Blum J, Tani N, Ikeda T, Artlett CM
Journal of Clinical Research in Pediatric Endocrinology, 12:160-167, 2020

Eissa MG, Artlett CM
Noncoding RNA, 12:5. pii: E23, 2019

Yasuoka H, Garrett SM, Nguyen XX, Artlett CM, Feghali-Bostwick CA
American Journal of Physiology Lung Cell Molecular Physiology, 316: L644-L655, 2019

Manley K, Bravo-Nuevo A, Minton AR, Sedano S, Marcy A, Reichman M, Tobia A, Artlett CM, Gilmour SK, Laury-Kleintop LD, Prendergast GC
Journal of Cell Biochemistry, 120:12051-12062, 2019

Artlett CM
Immunology Letters, 195:30-37, 2018

Ramanathan A, Mehta A, Artlett CM
Glycobiology Insights, 6:1-12, 2017

Artlett CM, Sassi-Gaha S, Hope JL, Feghali-Bostwick CA, Katsikis PD
Arthritis Research Therapy, 19:144, 2017. An editorial was written about this article.

Ghatak S, Hascall VC, Markwald RR, Feghali-Bostwick C, Artlett CM, Gooz M, Bogatkevich GS, Atnelishvili I, Silver RM, Thannickal VJ, Misra S
Journal of Biological Chemistry. 292:10490-10519, 2017

Hoffman W, Artlett CM, Boodhoo D, Gilliland M, Ortiz L, Mulder D, Tjan D, Martin A, Alexandru Tatomir A, Rus H
Experimental and Molecular Pathology, 102:505-514, 2017

Sargent JL, Li Z, Aliprantis AO, Greenblatt M, Lemaire R, Wu M, Wei J, Harris A, Long K, Burgwin C, Artlett CM, Blankenhorn EP, Lafyatis R, Varga J, Clark SH, Whitfield ML
Arthritis and Rheumatology, 68:2003-15, 2016

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