Yin Ren, MD, PhD, a distinguished physician-scientist at The Ohio State University Wexner Medical Center, is leading innovative research on neurofibromatosis and hearing loss. Dr. Ren, a neurotologist and assistant professor who joined the faculty of the Department of Otolaryngology – Head and Neck Surgery at The Ohio State University College of Medicine in 2021, has earned the prestigious Department of Defense (DOD) Neurofibromatosis Research Program Investigator-Initiated Research Award.
His project, titled Characterization of Novel Patient-Specific Modeling Systems for NF2 Disease Research and Therapeutic Testing, focuses on creating advanced patient-derived models to study neurofibromatosis type 2 (NF2), a rare genetic disorder often resulting in vestibular schwannomas, tumors that impact hearing and balance. With limited treatment options, there’s an urgent need for new research in this area.
Dr. Ren and his team are working with researchers at Nationwide Children’s Hospital to create personalized models of NF2 tumors. They take skin cells from patients with NF2 and turn them into Schwann cells (the cells that form the tumors), which allows the researchers to study models that match each patient’s unique genetic makeup.
“This is a critical advancement, as it allows us to move beyond generic cell lines and study the disease in a way that truly mirrors the biology of each patient,” Dr. Ren says. “With these models, we can effectively test new drugs and therapies to identify the most promising approaches.”
Dr. Ren’s research addresses pivotal questions surrounding vestibular schwannomas: Why do some tumors grow rapidly while others don’t? Why does hearing loss occur in only certain patients? How can surgical outcomes be more accurately predicted? His lab uses advanced biology and nanotechnology to study how tumors grow and develop, with the goal of creating new nanoparticles to improve diagnosis and treatment.
“NF2 is a devastating condition that can severely impact a patient’s quality of life,” Dr. Ren says. “By developing more representative research models, we hope to gain new insights into the disease process and accelerate the development of more effective treatments.”
Dr. Ren is a co-investigator on this DOD-funded project. He and his team aim to develop advanced models using patient-derived cells and organoids (3D mini-organ-like structures grown in the lab) to mimic the complexity of NF2 better. These models will be powerful tools to study the underlying mechanisms of tumor formation and evaluate the efficacy of potential therapeutic interventions.
The researchers will also evaluate novel gene therapy approaches using adeno-associated virus vectors. The goal is to use gene therapy to restore the expression of missing genes in NF2 tumors, potentially halting or reversing tumor growth.
The team is testing gene therapy by implanting tumor cells from patients into the sciatic nerves of mice to create a model that closely resembles the tumor environment in people with NF2. This enables scientists to study how well the therapy works, find the right dose and ensure it’s safe before moving on to clinical trials.
Along with his DOD-funded work, Dr. Ren has also been awarded an internal grant from the Ohio State Clinical and Translational Science Institute for his project, Assessing Biomarkers of Hearing Loss in Vestibular Schwannomas and Other Disorders. This study focuses on identifying biomarkers to detect hearing loss associated with vestibular schwannomas and other conditions.
The project’s goal is to create a simple, cost-effective test that can identify biomarkers of hearing loss in the blood of people with NF2. Rather than requiring patients to undergo costly and time-consuming hearing tests, this new approach would allow for easy at-home monitoring.
“Most patients with NF2 live far from specialty centers, making it difficult to get the hearing assessments they need regularly,” Dr. Ren says. “Our team is working to develop a paper-based assay that can detect relevant biomarkers using just a small blood sample.”
The key innovation lies in the use of gold nanoparticles, which can amplify the signal of these low-abundance biomarkers. By coupling the paper-based test with specialized spectroscopy instruments, the researchers are working to create a highly sensitive diagnostic that could be widely deployed, even in resource-limited settings. The approach may also serve as a blueprint for detecting other clinically relevant biomarkers.