How substrate dosage drives prion disease kinetics

This project is focused on advancing understanding and management of Chronic Wasting Disease (CWD), an infectious prion disease affecting cervids including elk, deer, moose, and reindeer. With clinical experience in large and small animal veterinary medicine and expertise in transgenic mouse model characterization for neurodegenerative diseases, The project aims to understand CWD pathogenesis, early detection, genetic susceptibility, and potential human transmissibility.

Working with Montana Fish, Wildlife & Parks, the lab is determining the distribution of prion protein-related genetics among Montana's mule deer, white-tailed deer, and elk. By comparing samples collected from the first year CWD was identified in the state through the present timeframe, the effort seeks to detect whether genetic changes associated with partial resistance, altered susceptibility, or modified disease severity are already occurring in local populations. Identifying such genetic variation could inform wildlife management strategies, including region-specific adjustments in hunting pressure or other interventions designed to reduce transmission or preserve genetic lines with lower disease susceptibility. Another major research pillar in the Grindeland laboratory is the development of early disease identification methods in living animals.

Early detection of CWD would markedly improve surveillance and the timing of interventions intended to limit onward transmission. To address practical limitations inherent in wildlife testing, the lab uses powerful transgenic mouse models that recapitulate CWD to map the earliest neuropathological timepoints and to evaluate candidate live-testing approaches. Ongoing studies with these mouse models aim to identify reliable, humane, and field-applicable markers of early disease. Candidate approaches under investigation include blood-based markers indicative of brain and muscle damage, behavioral measures that track cognitive decline, and peripheral sampling of lymph nodes and spleen. The lab is also exploring fecal and urine markers that would enable noninvasive testing of live animals, practical use by hunters, and detection of environmental contamination.

These translational efforts are intended to bridge mechanistic insights from model systems to surveillance tools feasible for deployment in wildlife populations. Finally, recognizing a persistent gap in knowledge about human risk, the Grindeland laboratory is conducting investigations into the potential transmissibility of CWD to humans. Using sensitive, in-depth approaches to assay multiple markers of prion disease, the laboratory seeks to uncover prion characteristics that may have been previously unobserved and to clarify human health implications. The laboratory's research program is supported by the Center for Integrated Biomedical Research and Rural Health Research at the McLaughlin Research Institute, itself funded by the National Institute of General Medical Sciences of the National Institutes of Health. Collectively, these efforts aim to strengthen surveillance, inform management decisions, and deepen understanding of prion biology in both wildlife and potentially affected humans.