Dr. Debarshi Mustafi never imagined he would one day be at the forefront of revolutionizing genetic testing for retinoblastoma (Rb), but fate, passion, and the guidance of an inspiring mentor led him down this path. Originally from the southside of Chicago, Dr. Mustafi’s journey took him through medical training in Cleveland before landing at the University of Southern California (USC), where he trained under Dr. Jesse Berry, a leading expert in RB and a valued Medical Advisory Board Member at KnowTheGlow. During his residency at Children’s Hospital Los Angeles (CHLA), he was deeply influenced by Dr. Berry’s dedication to retinoblastoma and the power of early detection to save both vision and lives. Additionally, it was a pediatric retina specialist at CHLA, Dr. Tom Lee, who ultimately convinced him to specialize in retina, telling him that “the biggest bang for your buck is saving the vision of a child.” Dr. Mustafi holds this philosophy close, knowing that although the treatments for Rb can be harsh in the early years, they can offer a lifetime of sight in return.
As a pediatric retina specialist and researcher, Dr. Mustafi leads a lab dedicated to studying genetic diseases of the eye. His primary focus is on identifying mutations in retinal disease genes early to improve both clinical diagnosis and treatment outcomes. His work is centered on inherited retinal diseases and his path toRb genetics began serendipitously . Initially, he was developing a system to map genetic mutations for diseases adjacent to Rb1, the gene responsible for retinoblastoma. It wasn’t until his fellowship mentor, Dr. Andrew Stacey, approached him that he shifted his focus to Rb1 itself, launching a game-changing collaboration that led to the development of a faster, more reliable method for Rb genetic testing.
One of his most significant breakthroughs was determining which parent passed on the Rb1 mutation—without needing to test the parents. This discovery is critical because 90% of Rb cases that result in germline or heritable disease arise by chance, or de novo, which makes traditional family genetic testing ineffective in most cases. Dr. Mustafi and his team developed a way to identify Rb mutations from a child’s blood sample within 72 hours. The results were striking: children who have the Rb1 mutation that arises on the gene copy inherited from the father had significantly worse outcomes. These children presented at later stages and were more likely to lose an eye, and even in de novo cases, where the mutation was not inherited from a family member, the most severe cases occurred when inherited from the father.
Dr. Mustafi’s team discovered that they could identify the inheritance pattern due to a specific DNA modification called methylation, which alters the function of the Rb1 gene. They found a specific portion of Rb1 is not methylated on the paternal copy but it is methylated in the maternal copy which allowed them to understand the inheritance without having to test parents of an affected child. Understanding this pattern could transform how doctors approach Rb treatment. If a child’s Rb1 mutation comes from their father, it may indicate a higher risk of aggressive disease, allowing doctors to adjust treatment strategies early—perhaps treating more aggressively from the start or considering enucleation sooner to improve overall outcomes. His team is now investigating whether paternal inheritance of Rb1 mutations also increases the risk of secondary cancers later in life, a study that could have lifelong implications for Rb survivors.
For many Rb patients worldwide, genetic testing is not an option, especially in low-resource settings like sub-Saharan Africa. But thanks to Oxford Nanopore Technology, Dr. Mustafi’s work is poised to bring genetic sequencing into the field. A palm-sized sequencer can now read DNA anywhere, eliminating the need for high-powered machines. His team has also perfected a technique to use saliva instead of blood to extract DNA, making genetic testing much more accessible in remote areas where blood draws and storage are difficult. The cost of these advancements is surprisingly low. The device itself costs between $1,000 and $2,000, while full sequencing, including analysis, costs around $500 per patient.
Dr. Mustafi and his team are now focused on validating their findings with larger patient cohorts, beginning in the United States and expanding to global Rb centers. His long-term vision is to bring sequencing technology to regions where Rb diagnosis is currently challenging. Collaboration is key to making this vision a reality. His team is working with Dr. Jesse Berry at CHLA, St. Jude’s , and other Rb experts to ensure these breakthroughs reach the children who need them most. Thanks to an initial grant from the Gerber Foundation, what began as a search for a faster way to diagnose Rb has evolved into a path that could become globally transformative.
His passion for science and genetics runs deep. Both of his parents emigrated from India to the U.S. to pursue PhD research—his father in chemistry, working to design more effective MRI contrast agents c, and his mother in cancer research, focusing on colon cancer. Growing up in a research-driven household, Dr. Mustafi was inspired to blend genetics and medicine, a path that has now positioned him as a leader in retinoblastoma research. From his mentorship under Dr. Jesse Berry and Dr. Andrew Stacey to groundbreaking research that could shape the future of Rb treatment worldwide, Dr. Mustafi’s work is a testament to the power of science, collaboration, and a relentless pursuit of early detection. At KnowTheGlow, we are honored to share his story and look forward to the day when every child, no matter where they are, can access life-saving genetic testing.
