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 loalization 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 the 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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Positive and negative predictive values of topical steroid response for glaucoma induced by depot steroids

Mentor: Chan Nguyen, M.D., Ph.D.

Intravitreal and sub-Tenon’s steroid injections are useful for a number of ocular conditions including edema from diabetic retinopathy and retinal vein occlusions. However, use of these depot injections is hampered by the fear of inducing intractable glaucoma by steroid that cannot be removed once given. In contrast, the glaucoma induced by topical steroids is generally reversible once the drops are stopped. Although usually not useful as a treatment for posterior segment disease, topical steroids may serve as a useful test by which steroid-responsive individuals can be identified.

The goal of this retrospective study is to determine the positive and negative predictive values of topical steroid response for glaucoma induced by depot steroids. The patient population will include patients who were prescribed a course of topical steroids after pterygium excision and who subsequently underwent depot steroid injections for macular edema related to diabetes or retinal vein occlusion.

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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

Second- and third-year Ophthalmology residents are required to complete a research project, to be presented at the Annual Resident and Alumni Day on Saturday, June 11, 2016. 

Medical students are invited to assist the residents with their projects. This page will be updated once the residents confirm their projects, and research is underway.