Medical Student Research Projects

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.

Determining the domain-dependence of introducing tryptophan residues into distinct EGF domains

Mentor: John D. Hulleman, Ph.D., john.hulleman@utsouthwestern.edu

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. 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. However, it is unknown what would happen to fibulin-3 protein folding and secretion if we were to introduce a tryptophan mutation in other regions of the fibulin-3 protein. Would this tryptophan mutation be better tolerated in other similar, yet distinct EGF domains? Or does the presence of a tryptophan residue in any of the EGF domains have the same effect on fibulin-3 protein folding?

The goal of this project is to determine what happens to fibulin-3 secretion when we introduce similar, potentially pathogenic, tryptophan mutations in different EGF domains of the fibulin-3 protein.

The student who undertakes this study will develop a skill set enriched in molecular biology and cell biology techniques including: cloning, site-directed mutagenesis, aseptic cell culturing, mammalian cell transfection, luciferase assays, and western blotting. 

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

Mentor: John D. Hulleman, Ph.D., john.hulleman@utsouthwestern.edu

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. 

The effect of clinical experience on personal thresholds for the diagnosis and treatment of glaucoma suspects 

Mentor: Chan Nguyen, M.D., Ph.D., chan.nguyen@utsouthwestern.edu

Early glaucoma can be difficult to diagnose. A number of glaucoma risk calculators have been designed to help quantify the risk of a patient developing glaucoma over the next five years based on specific risk factors. However, most ophthalmologists use their own experience rather than these calculators in deciding the treatment course of any particular patient.

The goal of this retrospective study is to determine whether resident physicians who have less experience than attending physicians have a lower or higher threshold for labeling patients as glaucoma suspects and for initiating glaucoma treatment. This data will be useful to ophthalmology residents looking for guidance in establishing their own personal thresholds for the diagnosis and treatment of glaucoma suspects.

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

Mentor: Chan Nguyen, M.D., Ph.D., chan.nguyen@utsouthwestern.edu

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.