Cellular and molecular pathways driving Thyroid eye disease (TED)
TED, also referred to as Graves’ ophthalmopathy is the most common orbital pathology in the world. TED is an autoimmune disease that occurs in approximately half of patients with Graves’ disease. In TED, the tissues surrounding the eye (the orbit) become inflamed and ultimately remodel to form excessive fat deposits, scar tissue or a combination of both. Autoantibodies in TED activate orbital fibroblasts, which are the key effector cells in the disease, to form either adipocytes (type I disease) or scar-forming myofibroblasts (type II disease). It is unclear how TED develops and why in some patients, tissue remodels as fat, as scar tissue, or a mixture of both. We study molecular pathways in orbital fibroblasts from TED patients to understand the pathobiology of disease and identify new targets that may help treat and even cure TED.
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Scar formation in Proliferative vitreoretinopathy (PVR)
PVR is the leading cause of recurrent retinal detachments (RDs) and is a blinding disease process characterized by fibrotic membranes that develop on the retinal surface or within the retina in up to 10% of RDs. The main pathologic process in PVR is epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. EMT is driven by cytokines and growth factors in the vitreous, most notably transforming growth factor beta (TGFβ). Currently, there are no pharmacologic therapies that improve visual outcomes or decrease re-detachment rates for PVR patients. We study cell signaling pathways in RPE cells that drive EMT and proliferation to find new therapeutic targets that can stop PVR.
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High throughput screening (HTS) to identify novel inhibitors of scarring
Formation of excess scar tissue is one of the most significant problems associated with wound repair in the ocular orbit, retinal space and the cornea. Tissue scarring occurs through proliferation of myofibroblasts (scar forming cells), as well as myofibroblast-mediated deposition of extracellular matrix. There are few, if any, effective therapies to prevent excess scarring during wound healing. Thus, new directed therapies to prevent scar formation are urgently needed. Using fluorescent and luciferase-based reporter systems and diverse small molecule and genetic libraries, we aim to identify novel small molecule inhibitors that block excessive scar formation.
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Role of microRNAs (miRNAs) in ocular response to injury
MiRNAs are a class of small, non-coding RNAs that fine-tune target gene expression. MiRNAs usually reduce gene expression by base pairing or binding with target messenger RNAs (mRNAs) to suppress protein production and/or increase mRNA decay. Individual miRNAs can target several to hundreds of distinct mRNAs and therefore can significantly regulate cell physiology. Altered miRNA expression patterns are also potential biomarkers of disease. Additionally, specific miRNAs and miRNA inhibitors (antagomirs) may be novel therapeutic options. We study expression level changes and function of miRNAs in TED and PVR in order to better understand their role in pathophysiology and identify miRNA biomarkers of disease.
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