- October 16, 2026
- By Maryland Today Staff
A University of Maryland researcher has been named to a consortium that aims to predict how disease-causing proteins misfold before irreversible damage occurs and use those predictions to develop novel diagnostics and treatments.
The team, co-led by Georgetown University’s Priyanka Joshi and the Buck Institute for Research on Aging’s Chuankai (Kai) Zhou, was awarded up to $51.7 million by the Advanced Research Projects Agency for Health. The four-year effort is expected to lead to new ways of detecting, slowing and treating neurodegenerative diseases and cancer, with an initial focus on Alzheimer's disease and Ewing sarcoma.
University of Maryland Professor Pratyush Tiwary is a member of the team named SEEDS (Sequence-to-disease: Environment-aware Ensembles of Disordered proteins at Scale), which aims to generate the data needed to train artificial intelligence to recognize the rules governing disease-causing proteins and predict their behavior. Many of these proteins have long been considered "undruggable" because they lack the stable shapes and binding pockets that most drugs are designed to fit.
Tiwary will contribute as a co-principal investigator to INTREPID (INTegRated Environment-aware Prediction Engine for Intrinsically Disordered Protein Pathology), part of the consortium led by Georgetown, which will examine in depth how a protein’s sequence and cellular environment affect the range of shapes it can take and how it behaves. He and colleagues at Georgetown, along with industry partners, will combine high-throughput and high-resolution experimental measurements with computation and artificial intelligence.
“At the heart of INTREPID is a chemistry-first generative AI model that predicts how disordered protein ensembles change across cellular conditions such as pH, crowding, metabolites, oxidative stress and post-translational modifications,” said Tiwary, who holds appointments at the University of Maryland, College Park and the University of Maryland, Baltimore.
The INTREPID team will begin by studying a pair of intrinsically disordered proteins implicated in Alzheimer’s disease and Ewing sarcoma, a rare cancer. Unlike many proteins that adopt relatively stable 3D structures, intrinsically disordered proteins form many different shapes. Cellular conditions can influence which forms they take and how they behave. That flexibility allows intrinsically disordered proteins to perform important functions in healthy cells, but it also makes them extraordinarily difficult to understand and target when something goes wrong.
“Can we recognize when a protein is headed in a harmful direction before it gets there, and if so, can we change its course?” Joshi asked. “That question brought this team together.”
The goal is to move from describing these proteins one at a time to predicting their behavior from sequence and surroundings alike, and to turn that prediction into ways to detect, and ultimately prevent, the shifts that lead to disease. Importantly, the team will pair computational predictions with experimental measurements, testing protein behavior under different conditions rather than relying on computer models alone.
This article was adapted from text provided by Georgetown University.