Dr. Upadhyaya's past and ongoing research is focused on translational studies and clinical trials for children with brain and spinal cord tumors with a special emphasis on ependymoma and ATRT. Children with brain tumors continue to have poor outcomes compared to those with other cancers in this age group. 

Dr. Upadhyaya has analyzed the outcomes of treatment for ATRT and ependymoma in children, combining traditional modes of therapy, such as surgery, chemotherapy, and radiation therapy, with molecularly targeted therapy. In the process he has identified novel clinical and molecular risk factors associated with outcomes. By identifying clinical risk factors associated with poor outcomes in these children, he can tailor therapy to improve outcomes in those at highest risk of treatment failures.