Solving the Mystery of Thyroid Eye Disease

As the new Odd Fellows Rising Professor of Ophthalmology, Fatemeh Rajaii will get a big boost in her research pursuit.

Published in Wilmer - Annual Report 2022

Long-lasting institutions remain relevant by honoring their past while keeping their eye on the future. The Independent Order of Odd Fellows exemplifies this strategy. The fraternal order, formed in the 18th century in England, established its first American Odd Fellows lodge in Baltimore, Maryland, in 1819. Several centuries later, the Odd Fellows comprises 600,000 members in 30 countries and attracts members by offering a place to “take an active role in helping your community and the world be a better place.”

One way the order does so is through philanthropy. Since 1963, the Odd Fellows has supported the Wilmer Eye Institute through its Visual Research Foundation, and the organization has provided funding for three professors since then, including the current Odd Fellows Professor of Ophthalmology, Henry Jampel, M.D., M.H.S.

Building on the history of its relationship with Wilmer, the Odd Fellows recently endowed a rising professorship. Wilmer created rising professorships in 2021 to provide up to seven years of research funding and support to promising early-career faculty members. The inaugural group of endowed Rising Professors consists of four assistant professors of ophthalmology — including the new Odd Fellows Rising Professor of Ophthalmology Fatemeh Rajaii, M.D., Ph.D., an oculoplastic surgeon and clinician scientist.

“The reason we support a rising professorship is for the future,” says Mark Ulrich, chairman of the Odd Fellows Visual Research Foundation. “Through mentoring from Dr. Jampel and funding from the professorship, the goal is to help accelerate Dr. Rajaii’s research and clinical practices so hopefully in the future we can find a cure for some of the diseases that affect the eye.”

“Given challenges in funding for early career scientists, it is more crucial than ever today to provide support for our most promising early-career clinician scientists. With this latest Rising Professorship, the Order of Odd Fellows has further solidified the Wilmer Eye Institute as the place where young scientists can flourish in their work,” says Wilmer Director Peter J. McDonnell, M.D.

Rajaii’s work focuses on better understanding thyroid eye disease (TED), which is associated with autoimmune thyroid disease. Thyroid eye disease occurs when antibodies in the immune system that normally help the body fight infection mistakenly trigger a receptor on cells in the bony eye socket, or orbit. This sets off inflammation and an abnormal reaction in which the fatty tissues and muscles behind the eye expand.

“There’s really no place to put the extra tissue, so this can cause the eye to bulge or crush the optic nerve,” Rajaii says. Patients may also experience strabismus, or crossed eyes, which can lead to double vision, and, in rare cases, blindness.

Rajaii is intent on answering a basic science question: How do orbital fibroblasts, the target cells in the pathology of thyroid eye disease, differentiate to become new fat cells, which causes the expansion of the tissues behind the eye? “Despite all we know about thyroid eye disease, there are still many questions regarding the disease process, so the ultimate goal of my research is to learn more,” she says. Once the mechanics of the disease are better understood, then pathways and molecules could be targeted to develop novel therapies, she adds. This important line of research will now be possible for her to pursue, thanks to the Order of Odd Fellows.

For Rajaii, the key benefit of a rising professorship is the seven years of research funding. Like other early- career faculty, she has received a Career Development (K) Award to get her research off the ground. She will next apply for a Research Project (R01) grant. But nationwide, it takes an average of eight years for new faculty members to receive their first R01 grant, which could leave a funding gap of several years.

“The length of time of the rising professorships provides a cushion,” says Rajaii, who was drawn to ophthalmology because she felt the specialty would allow her to balance both clinical work and research. “The rising professorship will provide extra funding and time to maintain lab productivity and transition to the next step.”

When it comes to her Odd Fellows Rising Professorship, Rajaii is especially thankful to have funding to hire another staff member. In addition to her work examining thyroid eye disease, she has a second area of research working with Jonathan Ling, Ph.D., from pathology, and William Brian Dalton, M.D., Ph.D., from oncology, both faculty members at the Johns Hopkins School of Medicine. Together they are working to harness abnormalities in splicing — the process in which genes are converted into proteins — that occur within tumor cells to selectively target those tumor cells for treatment or cell death. Having another person in her lab is crucial to advancing these multiple lines of research.

“I still have clinical responsibilities so it’s hard to maintain the highest productivity with research when I’m not able to be there all the time,” she says. This additional person ensures research continues even as Rajaii attends to her other responsibilities. “It’s an amazing thought that the Odd Fellows had, to support this program.”