John Prensner obtained his Bachelor's degree in English Literature at Tufts University in 2005, and his MD and PhD degrees at the University of Michigan Medical School in 2014. His PhD focused on long noncoding RNAs in cancer. He then completed pediatric residency training at Boston Children’s Hospital in 2017 and a fellowship in pediatric hematology/oncology at Boston Children’s/Dana-Farber Cancer Institute in 2020. He conducted post-doctoral research with Dr. Todd Golub at the Broad Institute of MIT and Harvard, where he developed approaches to discover and characterize non-canonical translation in cancer. He joined the faculty at the University of Michigan in 2023. His lab focuses on the molecular basis of cancer, with a particular interest in pediatric brain cancers. His work uses high-throughput approaches to study RNA processing, RNA translation, and proteomics in cancer. His group also focuses on activation of the non-coding genome in cancer, resulting in RNA translation of non-canonical open reading frames. The goal is to use this information for improved therapeutics and drug development in cancer. Dr. Prensner has been the recipient of awards from the American Association for Cancer Research, the William Guy Forbeck Foundation, St. Baldrick's Foundation, Alex's Lemonade Stand Foundation, the ChadTough Defeat DIPG Foundation, the Hyundai Hope on Wheels Foundation, and the National Institutions of Health/National Cancer Institute.
Our research interests are in -omics approaches to pediatric cancer. We work to understand the RNA translation in the non-coding genome. We have worked in the following areas:
1. Non-canonical translation in cancer We use functional genomics to characterize oncogenic or tumor suppressive non-canonical open reading frames, which may encode small “miniproteins” excluded from prior genome-wide studies. We probe these bioactive miniproteins for new insights into cancer biology with an aim of novel target discovery through investigation of this “dark” proteome.
2. Translational dysregulation in cancer Many cancers dependent upon activation of the RNA translation machinery for survival. We use multi-omics approaches to elucidate patterns of translational regulation (or dysregulation) with an emphasis on pediatric cancers. We focus on the molecular determinants of these patterns of translational regulation, such as underlying oncogenic drivers.
3. RNA translation therapeutics in cancer We use pharmacologic approaches to inhibit various aspects of the RNA translation machinery and evaluate molecular determinants that predict response to these small molecule inhibitors. We define mechanisms governing efficacy of RNA translation inhibition and investigate pre-clinical support for use of these inhibitors in specific cancer settings.
4. The non-coding genome in cancer We use cancer profiling techniques to interrogate functional elements, disease loci, and novel genes in the non-coding genome of cancer.
Research Opportunities for Rotating Students
1. Control of RNA translation in pediatric brain cancers
2. RNA translation inhibitors for the treatment of cancer
3. Translation of endogenous retroviruses in diffuse intrinsic pontine glioma
4. Characterization of non-canonical open reading frames in cancer