Jeremy Nathans, an investigator at the Howard Hughes Medical Institute (HHMI) for nearly 40 years, has made significant contributions to the understanding of color vision, retinal diseases, and the Frizzled family of receptors, shaping various aspects of biomedical science. His research includes isolating the genes that influence human color perception and investigating the causes of multiple retinal disorders.
“My research program has been pretty eclectic,” Nathans said. “Vision research has been our central theme, but my students and I have enjoyed pursuing scientific questions beyond our comfort zone.”
Nathans’ journey in science began in a household of academic excellence; his father, Daniel Nathans, was a Nobel laureate who also became an HHMI investigator. Inspired by this environment, Nathans pursued his education in the sciences, earning degrees in chemistry and biology from MIT and later obtaining an MD-PhD at Stanford University.
His groundbreaking work on the genetic underpinnings of color vision initially involved studying light receptor proteins in the retina, culminating in the isolation of several key genes, including those for red and green cone receptors located on the X-chromosome. This discovery shed light on the genetic variations impacting red-green color vision.
Following his postdoctoral fellowship at Genentech, Nathans launched his own lab at Johns Hopkins Medical School, with a focus on helping patients suffering from severe visual impairments. His early work on retinitis pigmentosa revealed that mutations in the rhodopsin gene accounted for a significant number of cases. He later contributed to identifying the causes of other retinal conditions, including Stargardt disease and vitelliform macular dystrophy.
A serendipitous finding in his lab led to the identification of the Frizzled receptors, which play crucial roles in cellular orientation and development. This discovery not only connected to retinal biology but also highlighted molecular signals that regulate blood vessel growth in the retina and brain. Nathans identified that one protein, Norrin, interacts with Frizzled-4, impacting both vascular growth and the integrity of the blood-brain barrier.
These insights have propelled Nathans’ research into clinical applications, resulting in the development of a synthetic drug candidate aimed at activating Frizzled-4. This candidate is currently undergoing testing in a Phase 3 clinical trial for diabetic retinopathy, with Nathans serving as a scientific advisor on the project.
As he prepares to step back from active research, Nathans aims to support early-career scientists through teaching and mentoring. He emphasizes the importance of passing on knowledge and resources to the next generation, stating, “Research funding is a zero-sum game, and I don’t want to consume more resources.” With a commitment to biotechnology and education, Nathans expresses his desire to remain useful in advancing patient care and knowledge in the field of vision science.
