DS-AI Seed Grants: Epigenetic Variation in Pituitary Pars Intermedia Dysfunction

Pituitary pars intermedia dysfunction (PPID, previously known as equine Cushing’s syndrome) is a neurodegenerative condition affecting up to one in four aged horses that causes significant disease and even euthanasia. This disease occurs when neurons in the brain (hypothalamus) degenerate, which causes unregulated growth of cells in the pituitary gland. Interestingly, the changes happening in a PPID-affected horse’s brain look very similar to the changes seen in the brains of people with Parkinson’s disease and related Lewy body dementia. The similarity between PPID and Parkinson’s/Lewey body patients creates an opportunity to capitalize on what is known in Parkinson’s disease and related brain conditions as we investigate PPID. Additionally, if we find genetic and epigenetic changes in horses PPID that are similar the changes in Parkinson’s patients’ brains, this will further show the horse’s potential to serve as a model for brain and synucleinopathy research. PPID spontaneously occurs much more frequently than Parkinson’s disease (~20% in horses with PPID vs. 1% in human Parkinson’s) making PPID easier to study. 

A project led by Professor Molly McCue (Veterinary Population Medicine; MSI PI) is exploring changes in methylation patterns in horses with PPID that can lead to particular genes being turned on and off in affected horses’ brains by sequencing their genomes with Oxford Nanopore long-read sequencing. Graduate student and MSI user Lauren Hughes is a co-investigator on the project. This work will allow the exploration of the contribution of genetic alterations and gene expression to disease risk and curate a catalog of epigenetic variation in the aged horse that can serve as a resource for both horse and human researchers. Data accessibility and usage will be assured using multifaceted approach, including: 1) disseminating a genomic and epigenomic data processing computing pipeline; 2) hosting data on the University of Minnesota Gems Informatics Platform; and 3) incorporating the catalog of epigenetic variation into a Shiny App to allow data exploration. 

This project received a DSI Data Sets Seed Grant in 2024 and was featured during the Seed Grant Showcase in February 2025. The Seed Grant program promoted, catalyzed, accelerated, and advanced University of Minnesota-based data science research so that University faculty and staff are well prepared to compete for longer term external funding opportunities. 

DSI became the Data Science and AI Hub (DSAI) in June 2025. The DSAI Seed Grant program is currently paused and they are not accepting proposals. More information can be found on the Seed Grant website.

graphical abstract of the project