Medical Student Research Projects

Projects with Ophthalmology Faculty

Throughout the year, Department of Ophthalmology faculty members welcome medical student involvement in research projects. Medical students interested in pursuing research in the Department of Ophthalmology should review the topics below and contact the faculty member directly.

Identification of the subcellular localization of wild-type and mutant fibulin-3

Mentor: John D. Hulleman, Ph.D.

The rare retinal dystrophy, Malattia Leventinese, is caused by a mutation of an arginine residue at the 345th position in a protein called fibulin-3. Instead of incorporating an arginine residue, a change in the DNA code results in the insertion of a large, bulky tryptophan residue, thus the mutation is called Arg345Trp (R345W). This mutation site occurs in a specific region of the protein called an epidermal growth factor (EGF) domain.

The presence of this large tryptophan residue causes problems with fibulin-3 protein folding and its eventual secretion from cells. As a result, the disease-causing mutant protein is poorly secreted and has a tendency to activate the cell’s stress responsive signaling pathways.

In healthy individuals, misfolded proteins are normally recognized by the cellular quality control machinery and targeted for degradation, effectively removing them from the cell. However, an interesting aspect of this R345W mutation is that it is not effectively degraded within the cell. This observation begs the question: Where is mutant fibulin-3 located within the cell that renders it resistant to degradation? Is it localized in vesicles? Is it trapped in the Golgi apparatus? Can we identify ways to target mutant, disease-causing fibulin-3 for degradation?

The overall goal of this project is to determine the intracellular localization of wild-type (normal) and R345W (mutant) fibulin-3 in human retinal pigmented epithelial cells.

The student who undertakes this study will develop a skill set enriched in molecular biology and cell biology techniques including: aseptic cell culturing, mammalian cell transduction, immunohistochemistry, epifluorescence microscopy, and confocal microscopy.

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Generation of high-throughput-capable fusion proteins for identifying new drugs to treat retinal diseases

Mentor: John D. Hulleman, Ph.D.

A number of retinal disorders are caused by genetic mutations in genes encoding for secreted proteins. Many of these mutations compromise protein folding, and thus cause a defect in the protein’s secretion efficiency. Identifying compounds which rescue the mutant protein’s secretion defect is of substantial interest to my lab. However, since a cell at any given time secretes tens of thousands of proteins, it is difficult to specifically monitor the secretion of the one protein.

Researchers have therefore developed reporter assays to follow a single protein by modifying it and making it unique compared to the rest of the cell’s proteome. One such reporter assay strategy is to fuse is a light-generating enzyme (luciferase) to the protein of interest. Then, using an assay to detect the amount light given off in a sample, researchers can infer how much protein of interest is present. Such an approach can be useful for identifying new potential drugs which rescue the secretion defects using unbiased screening techniques in a high-throughput manner.

The goal of this project will be to use the Gaussia luciferase or Nano luciferase as a way to follow the secretion of retinal disease-associated proteins. Following the successful establishment and validation of this assay, the student will perform small-scale high-throughput screening experiments to identify drugs which may rescue the secretion of the mutant protein.

The student who is assigned to this project will develop skills associated with molecular biology, cell biology, and high-throughput screening. Specifically, s/he will be taught molecular cloning, luciferase assay development, cell culture, high-throughput screening, secondary assay verification, and quantitative PCR.

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Unilateral hereditary retinal dystrophy?

Mentor: Chan Nguyen, M.D., Ph.D.

Retinal dystrophies are almost by definition bilateral. However, there is a young Parkland patient with a unilateral lesion who claims that three of her brothers also suffered vision loss in only one eye at a young age. Project involves contacting the patient and bringing family members in to see if the case is reportable.

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True access to care

Mentor: Chan Nguyen, M.D., Ph.D.

There are various figures normally quoted for the percentage of physicians who accept Medicaid, but these figures may not represent the true access to care for these patients. This project involves calling various local physician offices to try to obtain a regular appointment or an urgent appointment for a vision-threatening condition that requires surgery. Results will be published in a report put forth by the Dallas County Medical Society's Access to Care and Vulnerable Populations Committee.

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Autologous serum tears for the treatment of dry eye

Mentor: Chan Nguyen, M.D., Ph.D.

Serum tears have been shown to be effective for various corneal surface disorders related to autoimmune disease. While these conditions are rare, dry eye disease is not, and studies of the effectiveness of serum tears for the treatment of dry eye have been limited in scope and in size. This project would involve drawing subjects' blood, centrifuging it to produce the serum, and then assessing subjects' ocular surface health after use of the drops for two weeks.

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Comparison of the Effectiveness of Lucentis versus Eylea for Avastin Failures

Mentor: Chan Nguyen, M.D., Ph.D.

Anti-VEGF agents have revolutionized the way macular edema from diabetes and retinal vein occlusions is treated. Avastin is the least expensive anti-VEGF agent available, with the cost of a single injection being ~$25. Lucentis and Eylea cost ~$1,500 per injection. As a result, Avastin is frequently the first-line anti-VEGF agent. However, many patients fail Avastin therapy, and there are no prospective studies that address which second-line therapy is better.

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Driving practices of visually impaired patients in a large county hospital eye clinic

Mentor: Chan Nguyen, M.D., Ph.D.

Most states have laws requiring physicians to report patients with seizures to the Department of Motor Vehicles. However, no such laws exist for visually impaired patients. In this prospective questionnaire-based IRB-approved study, Parkland patients not meeting the Texas vision standard for an unrestricted driver’s license will be questioned about their driving habits and license status. This will help determine the potential scope of the problem of unreported visually impaired drivers.

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Projects with Ophthalmology Residents

Medical students are invited to assist the residents with their projects listed below:

Vlad Matei, M.D. (PGY3)

Contact: mmath1185@gmail.com

Project: This project will study the course of hydroxychloroquine (Plaquenil) retinopathy after cessation of therapy. Hydroxychloroquine retinopathy has emerged as an important topic in the last few years because the medication is commonly prescribed. Although the damage from this condition is often permanent, and can progress for years even after stopping hydroxychloroquine, very little literature is available regarding the progression of the disease.

Responsibilities: Assist in chart review, and studying images of various ophthalmic tests used to monitor hydroxychloroquine retinopathy. The goal of this project is to publish the findings in a peer-reviewed journal.

Faculty Advisor: Yu-Guang He, M.D.

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