Laboratory and Field
Much of our current work involves chronic wasting disease (CWD) of cervids and other protein misfolding diseases in animals and humans. Research includes the discovery and advancement of novel prion detection methods and understanding the complicated ecological factors in the spread of CWD.
In the study of neurodegenerative diseases, understanding human influences is as important as the basic science conducted in the laboratory and field. Our current projects include engaging the public with hands on educational tools and learning the cultural perspectives and community impacts of diseases such as CWD.
3D anatomical models
Expanding the testing capabilities of RT-QuIC (real time quaking-induced conversion).
Team: Peter Larsen, Sang-Hyun Oh, Jeremy Schefers, Jason Bartz, Qi, Yuan, Stuart Lichtenberg, Michelle Carstensen, Linda Glaser, Davis Seelig, Marc Schwabenlander, Gage Rowden, Suzanne Stone, Manci Li, Evan Kipp, Adam Reinschmidt, Sarah Gresch, Fred Schendel, Tom Douville, Rachel Shoemaker, Steve Demarias, Miranda Huang
Groups: UMN College of Veterinary Medicine, UMN Biotechnology Resource Center, Creighton University, MN Department of Natural Resources, MN Board of Animal Health, University of Wisconsin
Assist with the establishment and coordination of a national RT-QuIC diagnostic network
Advance RT-QuIC capabilities for the detection of prion and protein-misfolding diseases
Background: RT-QuIC is a quantitative, high-throughput assay that exploits a fundamental aspect of prion biology to facilitate the detection of minute quantities of misfolded prions. In RT-QuIC, an infectious seed (or test sample) is incubated with an excess of recombinant prion protein. Then, over the course of 24-72 hours of shaking in the presence of a specific fluorescent dye, a real-time readout of prion accumulation is generated. This assay can provide an estimate of the presence and relative titer of misfolded prions from different types of samples. RT-QuIC has been used to accurately detect misfolded prions (including CWD prions) in the body fluids and tissues of humans and animals, including from animals at sub-clinical stages of infection and animals that tested negative by first-generation diagnostic tests (i.e., ELISA and IHC).
Epidemiological and laboratory validation of RT-QuIC for animal tissue sample CWD testing
Routine CWD testing protocols for: plant tissues, soil, water, feces, blood, muscle, environmental swabs
Expansion of RT-QuIC to other neurodegenerative diseases
Provide protocols and reagents for RT-QuIC
Funders: Minnesota State Legislature through Rapid Agricultural Response Fund (RARF); Environment and Natural Resources Trust Fund through the Legislative-Citizen Commission on Minnesota Resources; University of Minnesota Office of the Vice President for Research, United States Department of Agriculture
Innovative 3D anatomical models for advancing veterinary education, disease surveillance sampling, and food safety inspection services.
Team: Roxanne Larsen, Marc Schwabenlander, Arthur Erdman, Paul Rothweiler, Shana Tanenbaum, Sadhika Prabhu, Emily Graba, Adam Landon
Groups: UMN College of Veterinary Medicine, UMN College of Science and Engineering, Earl E. Bakken Medical Devices Center, MN DNR
Improve disease surveillance and food safety through improved training.
Forge collaborations in training, education, and outreach.
Background: There exists a broad need to develop advanced, anatomically accurate 3D models, and associated digital videos, to assist in training food inspectors, consumer safety inspectors, and diagnostic sample collectors. This affects a multitude of disciplines including field-based sample collection, such as surveillance for chronic wasting disease, as well as public health veterinarians at meat inspection and processing plants, and instructors who teach food animal production courses or wildlife and natural resource management courses at colleges and universities.
Projected outcomes: Develop a research-validated collection of physical and virtual multi-species 3D animal models that can be utilized on a wide scale for sample collectors, trainers, educators, and inspectors.
Funders: UMN College of Veterinary Medicine Dean’s office; UMN Office of the Vice President for Research
CWD test development
Development of advanced CWD diagnostic and detection tools.
Team: Peter Larsen, Sang-Hyun Oh, Helen Dooley, Seelig Davis, Pam Skinner, Jeremy Schefers, Marc Schwabenlander, Gage Rowden, Peter Christenson, Manci Li, Dong Jun Lee, Rachel Shoemaker
Groups: UMN College of Veterinary Medicine, UMN College of Science and Engineering, University of Maryland
Goals: Our team has launched several research projects aimed at advancing second-generation and developing novel third-generation CWD diagnostic tools for animal testing and environmental monitoring. To accomplish this task, we are focusing on:
Cervid genome sequencing and identifying novel blood-based biomarkers that can identify early stages of CWD infection.
Nanoparticle interaction with and detection of CWD causing prions.
Development of microfluidic technology capable of detecting CWD causing prions in a wide variety of samples collected from hunter-harvested deer, live deer, and/or the environment (e.g., feces, soil).
Discovery and engineering of new antibodies for the advancement of current and future tests and therapeutics.
Development of prion imaging-based diagnostic tools.
Background: Robust and easy-to-use diagnostic tests for CWD are currently unavailable. Existing CWD diagnostic tools are cumbersome, time-consuming, and require significant technical expertise. For these reasons, routine testing of venison for CWD is a difficult task and it is estimated that between 15,000 and 20,000 CWD positive deer are consumed in the US annually, with a projected 20% annual increase. Current CWD diagnostic tests can be classified into two categories, first-generation “gold standard” antibody-based diagnostics (e.g. IHC, ELISA) and second-generation prion protein amplification assays. Given increasing concern that CWD will continue its spread throughout Minnesota, North American, and global deer populations, there is an immediate and critical need to advance prion detection methods and develop advanced third-generation CWD diagnostics tools. Third-generation CWD diagnostic tests will leverage emerging microfluidic and nanotechnologies that are being developed for a variety of biomedical applications.
Development of CWD-specific diagnostic RNA panel that can be used with both live and recently harvested deer.
Development of novel microfluidic biosensors capable of fine-scale detection of the CWD causing prion.
Identification of prion-specific antibodies that can be used for novel antibody-based CWD diagnostics.
Funders: Minnesota State Legislature through Rapid Agricultural Response Fund (RARF); Environment and Natural Resources Trust Fund through the Legislative-Citizen Commission on Minnesota Resources; University of Minnesota Office of the Vice President for Research
Engaging culturally-diverse hunting communities on CWD.
Team: Tiffany Wolf, Adam Landon, David Fulton, Lauren Bernstein, Seth Moore, Travis Bartnick, Kelly Applegate, Eric Clark, Marc Schwabenlander, Colin Yoder, Roger Faust
Groups: UMN College of Veterinary Medicine, UMN College of Food, Agricultural and Natural Resource Sciences, Grand Portage Band of Lake Superior Chippewa, Mille Lacs Band of Ojibwe, Sault Ste. Marie Tribe of Chippewa Indians, Shakopee Mdewakanton Sioux Community, Red Lake Band of Chippewa Indians, Keweenaw Bay Indian Community, Prairie Island Island Community, Bad River LaPointe Band of the Lake Superior Tribe of Chippewa Indians, Lower Sioux Indian Community, Fond du Lac Band of Lake Superior Chippewa, Leech Lake Band of Ojibwe, White Earth Chippewa, Bay Mills Indian Community, Little River Band of Ottawa Indians, Little Traverse Bay Bands of Odawa Indians, Red Cliff Band of Lake Superior Chippewa, Lac du Flambeau Band of Lake Superior Chippewa, Great Lakes Indian Fish & Wildlife Commission, Minnesota Hmong Community, Minnesota Amish Communities, MN Department of Natural Resources
Engage in culturally-appropriate CWD outreach and education.
Learn more about community-specific hunting behavior and perceptions of CWD management on Tribal lands.
Establish connections with leaders and members of our Native American, Southeast Asian, and Amish communities for continued information sharing.
Background: The success of Minnesota’s efforts to control CWD in white-tailed deer hinges on the ability of government agencies, researchers, policy makers and stakeholders to work together, particularly as this issue relates to deer hunting as a CWD management tool. However, in December 2019, our team became aware that culturally-diverse hunting communities had not received critical information regarding CWD biology, management and potential human health risks. Special outreach efforts are needed to reach diverse stakeholders, such as our Minnesota Tribal Nations and Southeast Asian and Amish communities.
Projected outcomes: Advance community knowledge of CWD and the science behind agency control strategies, which supports the key outcome of inclusive, community-based CWD management.
Funders: Environment and Natural Resources Trust Fund through the Legislative-Citizen Commission on Minnesota Resources; United States Fish and Wildlife Service; United States Department of Agriculture, Animal and Plant Health Inspection Service; Great Lakes Indian Fish and Wildlife Commission
Ecology of CWD
Tribal CWD surveillance
The emergence of CWD in Minnesota: transmission across a landscape of plants, soils, water, and deer.
Team: Eric Seabloom, Peter Larsen, Tiffany Wolf, Elizabeth Borer, Diana Karwan, Joseph Bump, James Forester, Davis Seelig, Alex Strauss, Marc Schwabenlander, Gage Rowden, Anita Porath-Krause, Jason Bartz, Anu Wille, Maddie Grunklee, Sarah Gresch, Rachel Shoemaker, Stuart Lichtenberg
Groups: UMN College of Veterinary Medicine, UMN College of Biological Sciences; Food, Agriculture and Natural Sciences; University of Georgia, University of Wisconsin, Creighton University
Goals: We have assembled an interdisciplinary team that includes experts in disease ecology, geospatial modeling, hydrology, wildlife epidemiology, and prion ecology to investigate the environmental impacts of CWD in Minnesota. Our research effort will lead to the production of CWD risk maps for the entire state and will lay the foundation for future questions, research, and funding focused on the environmental impact and multifaceted transmission routes of CWD-causing prions.
Background: Research focused on the transmission of prion diseases at the ecosystem scale is lacking. For both CWD and scrapie, disease-causing prions enter the environment via host excretions or carcasses and can remain infectious for years or even decades. Recent research has shown that CWD prions in the environment can be dispersed by water, bound by soil, acquired by plant roots, transported to aboveground plant tissues, and transmitted to mammals that contact or consume contaminated plants. This new knowledge, along with emerging strains of infectious prions, has fueled concerns of transmission via water and a wide range of agricultural commodities.
Projected outcomes: This work will elucidate potential CWD transmission routes and environmental reservoirs for CWD-causing prions through integrated empirical and modeling approaches. These results will help combat the spread of CWD in Minnesota and mitigate future economic and environmental impacts. Products stemming from our work will include:
A synthesis of environmental CWD data from Colorado, Wyoming, and Wisconsin and an assessment of the relevance of these data for spread in Minnesota.
An epidemiological model parameterized with project data to assess key processes shaping transmission through deer, plants, water, and soil.
An intensive field study tracking the environmental spread of CWD in southeastern Minnesota as this disease emerges in real time.
A spatial model incorporating CWD movement via deer, scavengers, and water across Minnesota landscapes, generating preliminary statewide risk maps.
Funders: MN Futures 2020 through the UMN Office of the Vice President for Research; Environment and Natural Resources Trust Fund through the Legislative-Citizen Commission on Minnesota Resources; Clean Water Funds through the Minnesota Legislature
Development of a regional chronic wasting disease surveillance and management program in Native American lands.
Team: Tiffany Wolf, Seth Moore, Travis Bartnick, Kelly Applegate, Eric Clark, Marc Schwabenlander, Bill Severud, Maddie Grunklee, Colin Yoder, Madeline Struck, Roger Faust
Groups: UMN College of Veterinary Medicine, Grand Portage Band of Lake Superior Chippewa, Mille Lacs Band of Ojibwe, Sault Ste. Marie Tribe of Chippewa Indians, Shakopee Mdewakanton Sioux Community, Red Lake Band of Chippewa Indians, Keweenaw Bay Indian Community, Prairie Island Island Community, Bad River LaPointe Band of the Lake Superior Tribe of Chippewa Indians, Fond du Lac Band of Lake Superior Chippewa, Bay Mills Indian Community, Little River Band of Ottawa Indians, Little Traverse Bay Bands of Odawa Indians, Red Cliff Band of Lake Superior Chippewa, Lac du Flambeau Band of Lake Superior Chippewa, Great Lakes Indian Fish & Wildlife Commission
Goals: Develop consistent and efficient surveillance in Native American lands and for tribal hunters and natural resource managers of Minnesota, Wisconsin, and Michigan.
Develop a surveillance program with partnering tribes and intertribal agencies.
Contribute screened samples to CWD test development underway in MNPRO.
Develop a team of MN, WI, and MI tribal CWD leads.
Evaluate a mechanism to continue effective surveillance in MN, WI, and MI Native American lands.
Background: There is a need for consistent wildlife disease surveillance in Native American lands. Tribes in the U.S. are among the most systematically disadvantaged communities, suffering economic, social, and institutional inequities. Wildlife health and disease issues are challenging to address due to small tribal governments and insufficient resources. MN, WI, and MI tribes do not have reliable and rapid mechanisms to test harvested subsistence species for the presence of diseases like CWD. Currently, CWD surveillance among tribes is sporadic and inconsistent. With increased CWD prevalence in the midwest, there is strong interest among tribes to survey for this disease as they work to protect their resources. We hope that by establishing systematic CWD surveillance across the geographic spread of where tribal hunters harvest deer in MN, WI, and MI, tribes can contribute to the prevention of spread and potentially also protect moose range from CWD.
Projected outcomes: The information gained from this project will benefit the Chippewa and Dakota tribes of the upper midwest, all of which share jurisdictional boundaries and are working to promote the perpetuation of subsistence species. Establishing a regional tribal CWD surveillance program will enable MN, WI, and MI tribes to protect this subsistence lifestyle by contributing to the prevention of spread of wildlife disease.
Funders: United States Fish and Wildlife Service; United States Department of Agriculture, Animal and Plant Health Inspection Service
Circadian rhythm stabilization
CWD information evaluation
Investigating the evolution of circadian networks in the human brain.
Team: Peter Larsen, Manci Li
Groups: UMN College of Veterinary Medicine
Goals: To identify therapeutic targets for circadian rhythm stabilization in patients suffering from psychiatric and neurodegenerative disorders.
Background: The disruption of circadian rhythm is a hallmark of many human-specific psychiatric disorders and neurodegenerative diseases. Although several hypotheses have been proposed for the origin of this disruption, the underlying molecular processes remain enigmatic. To this end, our research effort focuses on a remarkable and emerging body of evidence that links primate-specific retrotransposons (Alu elements) to circadian network function. A number of recently published studies indicate the evolution of human-specific neuroepigenetic landscapes that unit circadian rhythms with Alu-centric post-transcriptional processes in the brain. We hypothesize that there exists a human-specific and dynamic synaptic transcriptome and proteome that is actively diversified by recently evolved Alus yet operates through functional epigenetic processes rooted in ancient circadian patterns of synaptic transmission. We are leveraging a diverse set of molecular tools to test the hypothesis that Alu retrotransposons participate in the organization of circadian brain function through multidimensional neuroepigenetic pathways.
Projected outcomes: We anticipate the identification of Alu-mediated neuroepigenetic processes that are closely tied to the evolution of human cognition. If accurate, the perturbation of these processes likely contributes to the manifestation of human-specific neurological diseases. The identification of relevant pathways will likely result in the production of novel therapeutics for several psychiatric and neurodegenerative disorders.
Funders: Foundation grant from Ann M. Saunders (President and Chief Executive Officer of Cabernet Pharmaceuticals) awarded to PI Larsen in memory of Dr. Allen Roses
Online CWD educational information assessment with a public health focus.
Team: Paige Palomaki, Marc Schwabenlander, Tiffany Wolf, Roxanne Larsen
Groups: UMN College of Veterinary Medicine and School of Public Health
Goals: Compare, contrast, and assess the content conveyed in CWD informational resources, general and specific to human health risks, that are publicly available online from sources within the United States in reference to factors such as source type, local presence of CWD, duration of CWD presence, etc.
Background: Public knowledge of and engagement around CWD is important for a multitude of reasons. Various members of the public can play an important role in the management and surveillance of CWD. Hunters play a role in population density management, an extremely important aspect of this disease which is perpetuated by close contact of animals and shared habitats that could harbor the infectious prions from shedding deer. Non-hunting members of the public can also play a role in the surveillance of the disease by being knowledgeable of clinical signs of CWD positive deer and knowing who to contact to remove the infected animal from the environment. Another important aspect relating CWD to public health is the human health and economic impacts of transmissible spongiform encephalopathies, the category of diseases that include CWD, scrapie and bovine spongiform encephalopathy (BSE). The aftermath of scrapie, which affects sheep, had significant economic impacts on the sheep industry. The BSE outbreak resulted in devastating economic and human health outcomes as the unknowns regarding the disease not only impacted the beef industry, but the consumption of BSE-infected meat resulted in humans developing variant Creutzfeldt-Jakob disease (vCJD), a fatal neurologic disease. Although CWD is principally a disease of cervids, CWD-causing prions exhibit strain variation and the entirety of its host range has yet to be clarified. A growing body of evidence suggests that CWD prion strain variation poses a risk to humans, with unique prion conformations serving as a potential source for prion-driven human neurodegenerative disease (i.e., Creutzfeldt-Jakob Disease). While CWD has not been directly linked to any human transmission to date, appropriate public education about the information we do know and do not know about the risk of CWD is important for the public to be empowered by knowledge rather than feel fearful of the unknown.