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2024-2025 Heed Fellows
FIVE KELLOGG TRAINEES WERE APPOINTED TO THE CURRENT CLASS OF THE PRESTIGIOUS SOCIETY OF HEED FELLOWS, RECEIVING MERIT AWARDS FOR POSTGRADUATE STUDIES IN OPHTHALMOLOGY.
During his residency at Kellogg, Warren Pan, M.D., M.Phil., Ph.D., worked in the lab of Thomas Wubben, M.D., Ph.D., and Cagri Besirli, M.D., Ph.D., two experts in the molecular pathways that drive blinding retinal diseases.
Now furthering his training with a vitreoretinal fellowship at Kellogg, Dr. Pan continues to study under these influential mentors and to pursue research in photoreceptor metabolism in inherited retinal diseases (IRDs).
“Consider that to date, just one FDA-approved treatment has been shown to be effective against just one of the more than 300 mutations implicated in the development of IRDs,” says Dr. Pan. “Many of those 300+ mutations are known to involve genes linked to cellular metabolism. Clearly, there is a pressing unmet need for more targeted therapies, especially those aimed at pathways, like PR metabolism, that are common to different IRDs.”
PR metabolism is a promising and largely unexplored area of IRD research. PRs require a great deal of energy to function. Yet unlike other cells that metabolize multiple energy sources, PRs metabolize only glucose. The process of breaking down glucose in PRs is driven by the enzyme pyruvate kinase muscle isozyme 2 (PKM2).
Dr. Pan is utilizing the small molecule MCTI-566, which activates PKM2. With funding from the Heed Foundation, he will test the ability of MCTI-566 to enhance the energy production and ultimate survival of PR cells.
“MCTI-566 may hold the key to novel, gene-agnostic treatments for IRDs,” says Dr. Pan. “It’s an exciting project with real translational potential.”
Rachana Haliyur, M.D., Ph.D., completed her residency at Kellogg in 2024, serving as co-chief resident in her final year. Prior to U-M, Dr. Haliyur earned a Ph.D. in molecular physiology and biophysics at Vanderbilt University, where she collaborated on groundbreaking research in diabetes, describing for the first time important connections between clinical data and functional testing in pancreatic tissue.
Rachana Haliyur, M.D., Ph.D., completed her residency at Kellogg in 2024, serving as co-chief resident in her final year. Prior to U-M, Dr. Haliyur earned a Ph.D. in molecular physiology and biophysics at Vanderbilt University, where she collaborated on groundbreaking research in diabetes, describing for the first time important connections between clinical data and functional testing in pancreatic tissue.
Dr. Haliyur credits her experiences as an ophthalmology resident with giving new focus to her diabetes research. “In my clinical training, I witnessed the devastating effects of vision loss driven by diabetes, which fueled my passion for translational research in this area,” she says. “I’m passionate about developing therapeutic targets and strategies to intervene early in the disease process, when vision can still be preserved.”
Vision loss in DR is believed to be driven at least in part by inflammation in the vitreous and retina. In collaborations with her two research mentors at Kellogg, Patrice Fort, Ph.D., and Rajesh C. Rao, M.D., Dr. Haliyur has developed a body of research suggesting that the inflammation that occurs in early stages of DR is different from that associated with the later, proliferative stage (PDR).
“My hypothesis is that in early-stage DR, inflammation arises from the body’s innate immunity, the protective system we are born with,” she explains. “Conversely, the adaptive immune system plays an important role in later stages of disease such as PDR.”
The Heed award will be applied to continue these studies. To identify early disease-driving immune events, Dr. Haliyur will study human tissue samples of DR and PDR. She hopes to better characterize immune responses in terms of specific gene expression and protein levels.
“Understanding the changing character of inflammation over the course of disease is a vital step in identifying molecular pathways unique to early-stage DR—pathways that can be targeted therapeutically,” she says. “I am grateful to the Heed Society for the opportunity to advance this work and continue to develop as a clinician-scientist. And I am excited about the potential of translational research like this to directly impact patients whose sight is threatened by diabetic retinal disease.”
As a resident at Kellogg, Daniel Balikov, M.D., Ph.D., worked with Rajesh Rao, M.D., and Noah Brown, M.D., investigating the genomic underpinnings of vitreoretinal lymphoma (VRL) and testing a new strategy of sampling ocular fluids to detect cell-free DNA (cfDNA) associated with VRL cells.
Surgically-obtained vitreous samples are usually examined with conventional pathology methods to make a diagnosis of VRL, but this often misses the mark. DNA from lymphocytes that cause VRL circulates in eye fluids. Drs. Rao, Brown, and Balikov have demonstrated the success of a new molecular diagnostic test targeting cfDNA from these fluids for VRL, improving the ability to diagnose it relative to conventional methods.
Now a vitreoretinal surgery fellow at the University of Miami’s Bascom Palmer Eye Institute in Florida, Dr. Balikov is applying the principles he practiced in cfDNA analysis to study endophthalmitis. A severe infection inside of the eye, endophthalmitis can result in catastrophic vision loss if not diagnosed and treated expeditiously.
“Early in my fellowship, I treated several patients with endophthalmitis and noticed that some displayed significantly more inflammation and toxic microbial activity than others,” he explains. “Those patients tended to have worse outcomes. If we could predict these responses earlier, we could do a much better job of triaging higher risk eyes for more aggressive treatment.”
Dr. Balikov hypothesizes that these more serious responses arise from microbial toxins and their possible mutations. Under the mentorship of Bascom Palmer retinal specialists Harry Flynn, M.D., Luis Haddock, M.D., and Darlene Miller, DHSc, he will develop a protocol to conduct whole genome sequencing on cfDNA obtained from patient samples.
“Our goal is to expand our understanding of the mechanism of endophthalmitis and identify new molecular targets for improved testing,” says Dr. Balikov. “I’m so grateful to the Heed Foundation for their support of this project and my continued development as a physician scientist.”
For Angela Gupta, M.D., Ph.D., receiving the Heed award coincides with arriving at Kellogg to begin a one-year fellowship in Cornea and External Disease.
Though her main focus in the year ahead is growing as a clinician and surgeon, Dr. Gupta is equally committed to continuing to build her research skillset, and to pursuing opportunities to improve the eye health of the medically underserved.
Dr. Gupta has already laid the foundation for a diverse research portfolio. While pursuing both an M.D. and Ph.D., her focus was basic research in glial cell biology. She expanded into clinical research as a resident. That work focuses on improving treatments for inflammatory corneal conditions and dry eye disease.
One of her projects involves an off-label ophthalmic application of Losartan which is used to treat high blood pressure and reduce stroke risk, but has also been shown to impact the transforming growth factor beta signaling pathway, which plays a key role in tissue health and repair.
“This has led to a proposed use of Losartan in eye drop form to treat corneal scarring,” she explains. “I am now analyzing data to determine its effectiveness.”
In 2023, Dr. Gupta co-authored a study of the expanded use of another medication—the nasal spray varenicline, which is FDA-approved to treat dry eye disease—for patients with Sjogren’s syndrome, an inflammatory condition that leads to dry eye disease.
“While the study sample was small, we saw a statistically significant improvement in tear production in these patients,” she reports.
Dr. Gupta also plans to continue her involvement in community interventions to address healthcare disparities in ophthalmology. As a resident, she organized diabetic retinopathy screenings for uninsured patients and investigated the socioeconomic factors influencing which patients received corneal crosslinking.
In recognition of her accomplishments, Dr. Gupta was one of ten 2024 recipients of the Resident Excellence Award from the American Society of Cataract and Refractive Surgery (ASCRS).
“I’m so grateful to be writing my next career chapter at Kellogg,” says Dr. Gupta, “and to receive this valuable support from the Heed Foundation.”
Now a vitreoretinal surgery fellow at Wills Eye Hospital in Philadelphia, P.A., Nikhil Bommakanti, M.D., completed his residency in 2023. He worked on several big data projects, most notably with Joshua Stein, M.D., during his residency at Kellogg.
He will apply his Heed fellowship to conduct two big data analyses of the safety and efficacy of biosimilar ranibizumab in eyes previously treated with branded ranibizumab for neovascular age-related macular degeneration (nAMD), diabetic macular edema, or macular edema following retinal vein occlusion, and in eyes which were not previously treated with any medication.
Ranibizumab and other anti-VEGF medications are biological products (biologics) used to treat retinal diseases such as nAMD. Biologics can be expensive, so there is an abbreviated Food and Drug Administration (FDA) approval pathway to encourage the development of biosimilar products (biosimilars).
The condensed approval pathway largely depends on analytical studies, resulting in comparatively smaller human clinical trials. Vision-threatening events have also been identified with other (non-biosimilar) medications after they were already approved by the FDA and were being used in clinic.
“This may be why surveys show that some retina specialists have concerns about the safety and efficacy of biosimilars,” notes Dr. Bommakanti.
Some biosimilars are also designated as ‘interchangeable biosimilars.’ The initial FDA guidance recommended a clinical study be performed, where medications are switched back and forth, before this designation being given. Interestingly, the biosimilar ranibizumab-eqrn (marketed as Cimerli®) was deemed interchangeable with the reference drug, Lucentis®, without a switching study.
“The dataset for these studies has more than ten times as many eyes as were included in the clinical trial for Cimerli®,” he says. “I’m excited to use big data to answer this practical and timely question.
